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Paul N Durrington - One of the best experts on this subject based on the ideXlab platform.
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effect of the human serum paraoxonase 55 and 192 genetic polymorphisms on the protection by high density lipoprotein against low density lipoprotein oxidative modification
FEBS Letters, 1998Co-Authors: Bharti Mackness, Michael I Mackness, S Arrol, Wajdi Turkie, Paul N DurringtonAbstract:Human serum paraoxonase (PON1) associated with high density lipoprotein (HDL) has been postulated to have a role in protecting low density lipoprotein (LDL) against oxidative modification, which has led to the proposal that PON1 is an anti-atherogenic, anti-inflammatory enzyme. PON1 has two genetically determined polymorphic sites giving rise to amino-acid substitutions at positions 55 (L→M) and 192 (R→Q) and therefore 4 potential Alloenzymes. We have examined the effects of these molecular polymorphisms on the ability of HDL to protect LDL from oxidative modification. HDL protected LDL from oxidative modification, whatever the combination of PON1 Alloenzymes present in it. However, HDL from QQ/MM homozygotes was most effective at protecting LDL while HDL from RR/LL homozygotes was least effective. Thus after 6 h of co-incubation of HDL and LDL with Cu2+ PON1-QQ HDL retained 57±6.3% of its original ability to protect LDL from oxidative modification, while PON1-QR HDL retained less at 25.1±4.5% (P<0.01) and PON1-RR HDL retained only 0.75±0.40% (P<0.005). In similar experiments HDL from LL and LM genotypes retained 21.8±7.5% and 29.5±6.6% (P=NS), respectively, of their protective ability, whereas PON1-MM HDL maintained 49.5±5.3% (P<0.01). PON1 polymorphisms may affect the ability of HDL to impede the development of atherosclerosis and to prevent inflammation.
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Effect of the human serum paraoxonase 55 and 192 genetic polymorphisms on the protection by high density lipoprotein against low density lipoprotein oxidative modification
FEBS letters, 1998Co-Authors: Bharti Mackness, Michael I Mackness, S Arrol, Wajdi Turkie, Paul N DurringtonAbstract:Human serum paraoxonase (PON1) associated with high density lipoprotein (HDL) has been postulated to have a role in protecting low density lipoprotein (LDL) against oxidative modification, which has led to the proposal that PON1 is an anti-atherogenic, anti-inflammatory enzyme. PON1 has two genetically determined polymorphic sites giving rise to amino-acid substitutions at positions 55 (L→M) and 192 (R→Q) and therefore 4 potential Alloenzymes. We have examined the effects of these molecular polymorphisms on the ability of HDL to protect LDL from oxidative modification. HDL protected LDL from oxidative modification, whatever the combination of PON1 Alloenzymes present in it. However, HDL from QQ/MM homozygotes was most effective at protecting LDL while HDL from RR/LL homozygotes was least effective. Thus after 6 h of co-incubation of HDL and LDL with Cu2+ PON1-QQ HDL retained 57±6.3% of its original ability to protect LDL from oxidative modification, while PON1-QR HDL retained less at 25.1±4.5% (P
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effect of the molecular polymorphisms of human paraoxonase pon1 on the rate of hydrolysis of paraoxon
British Journal of Pharmacology, 1997Co-Authors: Bharti Mackness, Michael I Mackness, S Arrol, Wajdi Turkie, Paul N DurringtonAbstract:1 The hydrolysis of organophosphate pesticides (OP) and nerve gases by serum paraoxonase (PON1) is an important factor determining their toxicity to mammals including man. The PON1 gene contains 2 polymorphic sites at amino acid positions 55 (LM) and 192 (GA, classically defined as the A and B genotypes) which result in several Alloenzymes of PON1 in human serum. 2 The 192 polymorphism has previously been shown to affect PON1 activity. We have investigated the effect of both polymorphisms on the hydrolysis of paraoxon by serum from 279 healthy human subjects. 3 The 55 polymorphism significantly influenced PON1 activity. MM homozygotes had over 50% less activity towards paraoxon compared to the LL and LM genotypes regardless of the 192 genotype (P<0.001). 4 Multiple regression analysis indicated that the 192 polymorphism, 55 polymorphism and serum PON1 concentration were responsible for 46, 16 and 13% of the variation in PON1 activity, respectively (all P<0.001). None of the other parameters investigated significantly affected PON1 activity. 5 Therefore both PON1 polymorphisms affect the hydrolysis of paraoxon. AA/MM and AB/MM individuals may be potentially more susceptible to OP intoxication. 6 Genotyping individuals for both PON1 polymorphisms may provide a method for identifying those individuals at most risk of OP poisoning. The effect of PON1 polymorphisms on activity may also explain why some Gulf War Veterans have developed Gulf War Syndrome and some have not. British Journal of Pharmacology (1997) 122, 265–268; doi:10.1038/sj.bjp.0701390
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Alloenzymes of paraoxonase and effectiveness of high-density lipoproteins in protecting low-density lipoprotein against lipid peroxidation.
Lancet (London England), 1997Co-Authors: Michael I Mackness, Bharti Mackness, S Arrol, Paul N DurringtonAbstract:Vol 349 • March 22, 1997 851 Our experience suggests that male-to-female transmission of HIV is infrequent during natural conception. Seroconversion occurring up to 3 months post-conception may be attributed to exposure up to the time of conception; no cases were observed. Counselling may help to reduce the risk of transmission, but this cannot be established from the number of couples followed in this study. It has been shown that there is a poor relationship between the number of acts of intercourse and the probability of transmission, indicating a great heterogeneity in infectivity. Our data may be biased being based on voluntary follow-up, and not a protocol. Some couples who did not return may have attempted to conceive unsuccessfully, and may not have reported seroconversions. Our findings are compatible with seroconversion rates in the order of 1 per 1000 episodes of unprotected intercourse reported in longitudinal studies of stable heterosexual couples, as well as in studies of transmission through artificial insemination. Some authors advocate intrauterine insemination with semen from the HIV-infected man, but the risk of this must be measured against the low background risk of natural conception. Stringent standards of safety must be required before inseminating potentially infective semen. Longitudinal virological studies are needed to evaluate whether interventions, including semen preparation, or antiretroviral therapies, can effectively clear cell-associated and cell-free virus from semen, thereby offering real hope for risk-free reproduction in “sero-different” couples.
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Effect of the molecular polymorphisms of human paraoxonase (PON1) on the rate of hydrolysis of paraoxon
British journal of pharmacology, 1997Co-Authors: Bharti Mackness, Michael I Mackness, S Arrol, Wajdi Turkie, Paul N DurringtonAbstract:1 The hydrolysis of organophosphate pesticides (OP) and nerve gases by serum paraoxonase (PON1) is an important factor determining their toxicity to mammals including man. The PON1 gene contains 2 polymorphic sites at amino acid positions 55 (LM) and 192 (GA, classically defined as the A and B genotypes) which result in several Alloenzymes of PON1 in human serum. 2 The 192 polymorphism has previously been shown to affect PON1 activity. We have investigated the effect of both polymorphisms on the hydrolysis of paraoxon by serum from 279 healthy human subjects. 3 The 55 polymorphism significantly influenced PON1 activity. MM homozygotes had over 50% less activity towards paraoxon compared to the LL and LM genotypes regardless of the 192 genotype (P
Bharti Mackness - One of the best experts on this subject based on the ideXlab platform.
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effect of the human serum paraoxonase 55 and 192 genetic polymorphisms on the protection by high density lipoprotein against low density lipoprotein oxidative modification
FEBS Letters, 1998Co-Authors: Bharti Mackness, Michael I Mackness, S Arrol, Wajdi Turkie, Paul N DurringtonAbstract:Human serum paraoxonase (PON1) associated with high density lipoprotein (HDL) has been postulated to have a role in protecting low density lipoprotein (LDL) against oxidative modification, which has led to the proposal that PON1 is an anti-atherogenic, anti-inflammatory enzyme. PON1 has two genetically determined polymorphic sites giving rise to amino-acid substitutions at positions 55 (L→M) and 192 (R→Q) and therefore 4 potential Alloenzymes. We have examined the effects of these molecular polymorphisms on the ability of HDL to protect LDL from oxidative modification. HDL protected LDL from oxidative modification, whatever the combination of PON1 Alloenzymes present in it. However, HDL from QQ/MM homozygotes was most effective at protecting LDL while HDL from RR/LL homozygotes was least effective. Thus after 6 h of co-incubation of HDL and LDL with Cu2+ PON1-QQ HDL retained 57±6.3% of its original ability to protect LDL from oxidative modification, while PON1-QR HDL retained less at 25.1±4.5% (P<0.01) and PON1-RR HDL retained only 0.75±0.40% (P<0.005). In similar experiments HDL from LL and LM genotypes retained 21.8±7.5% and 29.5±6.6% (P=NS), respectively, of their protective ability, whereas PON1-MM HDL maintained 49.5±5.3% (P<0.01). PON1 polymorphisms may affect the ability of HDL to impede the development of atherosclerosis and to prevent inflammation.
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Effect of the human serum paraoxonase 55 and 192 genetic polymorphisms on the protection by high density lipoprotein against low density lipoprotein oxidative modification
FEBS letters, 1998Co-Authors: Bharti Mackness, Michael I Mackness, S Arrol, Wajdi Turkie, Paul N DurringtonAbstract:Human serum paraoxonase (PON1) associated with high density lipoprotein (HDL) has been postulated to have a role in protecting low density lipoprotein (LDL) against oxidative modification, which has led to the proposal that PON1 is an anti-atherogenic, anti-inflammatory enzyme. PON1 has two genetically determined polymorphic sites giving rise to amino-acid substitutions at positions 55 (L→M) and 192 (R→Q) and therefore 4 potential Alloenzymes. We have examined the effects of these molecular polymorphisms on the ability of HDL to protect LDL from oxidative modification. HDL protected LDL from oxidative modification, whatever the combination of PON1 Alloenzymes present in it. However, HDL from QQ/MM homozygotes was most effective at protecting LDL while HDL from RR/LL homozygotes was least effective. Thus after 6 h of co-incubation of HDL and LDL with Cu2+ PON1-QQ HDL retained 57±6.3% of its original ability to protect LDL from oxidative modification, while PON1-QR HDL retained less at 25.1±4.5% (P
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effect of the molecular polymorphisms of human paraoxonase pon1 on the rate of hydrolysis of paraoxon
British Journal of Pharmacology, 1997Co-Authors: Bharti Mackness, Michael I Mackness, S Arrol, Wajdi Turkie, Paul N DurringtonAbstract:1 The hydrolysis of organophosphate pesticides (OP) and nerve gases by serum paraoxonase (PON1) is an important factor determining their toxicity to mammals including man. The PON1 gene contains 2 polymorphic sites at amino acid positions 55 (LM) and 192 (GA, classically defined as the A and B genotypes) which result in several Alloenzymes of PON1 in human serum. 2 The 192 polymorphism has previously been shown to affect PON1 activity. We have investigated the effect of both polymorphisms on the hydrolysis of paraoxon by serum from 279 healthy human subjects. 3 The 55 polymorphism significantly influenced PON1 activity. MM homozygotes had over 50% less activity towards paraoxon compared to the LL and LM genotypes regardless of the 192 genotype (P<0.001). 4 Multiple regression analysis indicated that the 192 polymorphism, 55 polymorphism and serum PON1 concentration were responsible for 46, 16 and 13% of the variation in PON1 activity, respectively (all P<0.001). None of the other parameters investigated significantly affected PON1 activity. 5 Therefore both PON1 polymorphisms affect the hydrolysis of paraoxon. AA/MM and AB/MM individuals may be potentially more susceptible to OP intoxication. 6 Genotyping individuals for both PON1 polymorphisms may provide a method for identifying those individuals at most risk of OP poisoning. The effect of PON1 polymorphisms on activity may also explain why some Gulf War Veterans have developed Gulf War Syndrome and some have not. British Journal of Pharmacology (1997) 122, 265–268; doi:10.1038/sj.bjp.0701390
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Alloenzymes of paraoxonase and effectiveness of high-density lipoproteins in protecting low-density lipoprotein against lipid peroxidation.
Lancet (London England), 1997Co-Authors: Michael I Mackness, Bharti Mackness, S Arrol, Paul N DurringtonAbstract:Vol 349 • March 22, 1997 851 Our experience suggests that male-to-female transmission of HIV is infrequent during natural conception. Seroconversion occurring up to 3 months post-conception may be attributed to exposure up to the time of conception; no cases were observed. Counselling may help to reduce the risk of transmission, but this cannot be established from the number of couples followed in this study. It has been shown that there is a poor relationship between the number of acts of intercourse and the probability of transmission, indicating a great heterogeneity in infectivity. Our data may be biased being based on voluntary follow-up, and not a protocol. Some couples who did not return may have attempted to conceive unsuccessfully, and may not have reported seroconversions. Our findings are compatible with seroconversion rates in the order of 1 per 1000 episodes of unprotected intercourse reported in longitudinal studies of stable heterosexual couples, as well as in studies of transmission through artificial insemination. Some authors advocate intrauterine insemination with semen from the HIV-infected man, but the risk of this must be measured against the low background risk of natural conception. Stringent standards of safety must be required before inseminating potentially infective semen. Longitudinal virological studies are needed to evaluate whether interventions, including semen preparation, or antiretroviral therapies, can effectively clear cell-associated and cell-free virus from semen, thereby offering real hope for risk-free reproduction in “sero-different” couples.
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Effect of the molecular polymorphisms of human paraoxonase (PON1) on the rate of hydrolysis of paraoxon
British journal of pharmacology, 1997Co-Authors: Bharti Mackness, Michael I Mackness, S Arrol, Wajdi Turkie, Paul N DurringtonAbstract:1 The hydrolysis of organophosphate pesticides (OP) and nerve gases by serum paraoxonase (PON1) is an important factor determining their toxicity to mammals including man. The PON1 gene contains 2 polymorphic sites at amino acid positions 55 (LM) and 192 (GA, classically defined as the A and B genotypes) which result in several Alloenzymes of PON1 in human serum. 2 The 192 polymorphism has previously been shown to affect PON1 activity. We have investigated the effect of both polymorphisms on the hydrolysis of paraoxon by serum from 279 healthy human subjects. 3 The 55 polymorphism significantly influenced PON1 activity. MM homozygotes had over 50% less activity towards paraoxon compared to the LL and LM genotypes regardless of the 192 genotype (P
Michael I Mackness - One of the best experts on this subject based on the ideXlab platform.
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effect of the human serum paraoxonase 55 and 192 genetic polymorphisms on the protection by high density lipoprotein against low density lipoprotein oxidative modification
FEBS Letters, 1998Co-Authors: Bharti Mackness, Michael I Mackness, S Arrol, Wajdi Turkie, Paul N DurringtonAbstract:Human serum paraoxonase (PON1) associated with high density lipoprotein (HDL) has been postulated to have a role in protecting low density lipoprotein (LDL) against oxidative modification, which has led to the proposal that PON1 is an anti-atherogenic, anti-inflammatory enzyme. PON1 has two genetically determined polymorphic sites giving rise to amino-acid substitutions at positions 55 (L→M) and 192 (R→Q) and therefore 4 potential Alloenzymes. We have examined the effects of these molecular polymorphisms on the ability of HDL to protect LDL from oxidative modification. HDL protected LDL from oxidative modification, whatever the combination of PON1 Alloenzymes present in it. However, HDL from QQ/MM homozygotes was most effective at protecting LDL while HDL from RR/LL homozygotes was least effective. Thus after 6 h of co-incubation of HDL and LDL with Cu2+ PON1-QQ HDL retained 57±6.3% of its original ability to protect LDL from oxidative modification, while PON1-QR HDL retained less at 25.1±4.5% (P<0.01) and PON1-RR HDL retained only 0.75±0.40% (P<0.005). In similar experiments HDL from LL and LM genotypes retained 21.8±7.5% and 29.5±6.6% (P=NS), respectively, of their protective ability, whereas PON1-MM HDL maintained 49.5±5.3% (P<0.01). PON1 polymorphisms may affect the ability of HDL to impede the development of atherosclerosis and to prevent inflammation.
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Effect of the human serum paraoxonase 55 and 192 genetic polymorphisms on the protection by high density lipoprotein against low density lipoprotein oxidative modification
FEBS letters, 1998Co-Authors: Bharti Mackness, Michael I Mackness, S Arrol, Wajdi Turkie, Paul N DurringtonAbstract:Human serum paraoxonase (PON1) associated with high density lipoprotein (HDL) has been postulated to have a role in protecting low density lipoprotein (LDL) against oxidative modification, which has led to the proposal that PON1 is an anti-atherogenic, anti-inflammatory enzyme. PON1 has two genetically determined polymorphic sites giving rise to amino-acid substitutions at positions 55 (L→M) and 192 (R→Q) and therefore 4 potential Alloenzymes. We have examined the effects of these molecular polymorphisms on the ability of HDL to protect LDL from oxidative modification. HDL protected LDL from oxidative modification, whatever the combination of PON1 Alloenzymes present in it. However, HDL from QQ/MM homozygotes was most effective at protecting LDL while HDL from RR/LL homozygotes was least effective. Thus after 6 h of co-incubation of HDL and LDL with Cu2+ PON1-QQ HDL retained 57±6.3% of its original ability to protect LDL from oxidative modification, while PON1-QR HDL retained less at 25.1±4.5% (P
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effect of the molecular polymorphisms of human paraoxonase pon1 on the rate of hydrolysis of paraoxon
British Journal of Pharmacology, 1997Co-Authors: Bharti Mackness, Michael I Mackness, S Arrol, Wajdi Turkie, Paul N DurringtonAbstract:1 The hydrolysis of organophosphate pesticides (OP) and nerve gases by serum paraoxonase (PON1) is an important factor determining their toxicity to mammals including man. The PON1 gene contains 2 polymorphic sites at amino acid positions 55 (LM) and 192 (GA, classically defined as the A and B genotypes) which result in several Alloenzymes of PON1 in human serum. 2 The 192 polymorphism has previously been shown to affect PON1 activity. We have investigated the effect of both polymorphisms on the hydrolysis of paraoxon by serum from 279 healthy human subjects. 3 The 55 polymorphism significantly influenced PON1 activity. MM homozygotes had over 50% less activity towards paraoxon compared to the LL and LM genotypes regardless of the 192 genotype (P<0.001). 4 Multiple regression analysis indicated that the 192 polymorphism, 55 polymorphism and serum PON1 concentration were responsible for 46, 16 and 13% of the variation in PON1 activity, respectively (all P<0.001). None of the other parameters investigated significantly affected PON1 activity. 5 Therefore both PON1 polymorphisms affect the hydrolysis of paraoxon. AA/MM and AB/MM individuals may be potentially more susceptible to OP intoxication. 6 Genotyping individuals for both PON1 polymorphisms may provide a method for identifying those individuals at most risk of OP poisoning. The effect of PON1 polymorphisms on activity may also explain why some Gulf War Veterans have developed Gulf War Syndrome and some have not. British Journal of Pharmacology (1997) 122, 265–268; doi:10.1038/sj.bjp.0701390
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Alloenzymes of paraoxonase and effectiveness of high-density lipoproteins in protecting low-density lipoprotein against lipid peroxidation.
Lancet (London England), 1997Co-Authors: Michael I Mackness, Bharti Mackness, S Arrol, Paul N DurringtonAbstract:Vol 349 • March 22, 1997 851 Our experience suggests that male-to-female transmission of HIV is infrequent during natural conception. Seroconversion occurring up to 3 months post-conception may be attributed to exposure up to the time of conception; no cases were observed. Counselling may help to reduce the risk of transmission, but this cannot be established from the number of couples followed in this study. It has been shown that there is a poor relationship between the number of acts of intercourse and the probability of transmission, indicating a great heterogeneity in infectivity. Our data may be biased being based on voluntary follow-up, and not a protocol. Some couples who did not return may have attempted to conceive unsuccessfully, and may not have reported seroconversions. Our findings are compatible with seroconversion rates in the order of 1 per 1000 episodes of unprotected intercourse reported in longitudinal studies of stable heterosexual couples, as well as in studies of transmission through artificial insemination. Some authors advocate intrauterine insemination with semen from the HIV-infected man, but the risk of this must be measured against the low background risk of natural conception. Stringent standards of safety must be required before inseminating potentially infective semen. Longitudinal virological studies are needed to evaluate whether interventions, including semen preparation, or antiretroviral therapies, can effectively clear cell-associated and cell-free virus from semen, thereby offering real hope for risk-free reproduction in “sero-different” couples.
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Effect of the molecular polymorphisms of human paraoxonase (PON1) on the rate of hydrolysis of paraoxon
British journal of pharmacology, 1997Co-Authors: Bharti Mackness, Michael I Mackness, S Arrol, Wajdi Turkie, Paul N DurringtonAbstract:1 The hydrolysis of organophosphate pesticides (OP) and nerve gases by serum paraoxonase (PON1) is an important factor determining their toxicity to mammals including man. The PON1 gene contains 2 polymorphic sites at amino acid positions 55 (LM) and 192 (GA, classically defined as the A and B genotypes) which result in several Alloenzymes of PON1 in human serum. 2 The 192 polymorphism has previously been shown to affect PON1 activity. We have investigated the effect of both polymorphisms on the hydrolysis of paraoxon by serum from 279 healthy human subjects. 3 The 55 polymorphism significantly influenced PON1 activity. MM homozygotes had over 50% less activity towards paraoxon compared to the LL and LM genotypes regardless of the 192 genotype (P
S Arrol - One of the best experts on this subject based on the ideXlab platform.
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effect of the human serum paraoxonase 55 and 192 genetic polymorphisms on the protection by high density lipoprotein against low density lipoprotein oxidative modification
FEBS Letters, 1998Co-Authors: Bharti Mackness, Michael I Mackness, S Arrol, Wajdi Turkie, Paul N DurringtonAbstract:Human serum paraoxonase (PON1) associated with high density lipoprotein (HDL) has been postulated to have a role in protecting low density lipoprotein (LDL) against oxidative modification, which has led to the proposal that PON1 is an anti-atherogenic, anti-inflammatory enzyme. PON1 has two genetically determined polymorphic sites giving rise to amino-acid substitutions at positions 55 (L→M) and 192 (R→Q) and therefore 4 potential Alloenzymes. We have examined the effects of these molecular polymorphisms on the ability of HDL to protect LDL from oxidative modification. HDL protected LDL from oxidative modification, whatever the combination of PON1 Alloenzymes present in it. However, HDL from QQ/MM homozygotes was most effective at protecting LDL while HDL from RR/LL homozygotes was least effective. Thus after 6 h of co-incubation of HDL and LDL with Cu2+ PON1-QQ HDL retained 57±6.3% of its original ability to protect LDL from oxidative modification, while PON1-QR HDL retained less at 25.1±4.5% (P<0.01) and PON1-RR HDL retained only 0.75±0.40% (P<0.005). In similar experiments HDL from LL and LM genotypes retained 21.8±7.5% and 29.5±6.6% (P=NS), respectively, of their protective ability, whereas PON1-MM HDL maintained 49.5±5.3% (P<0.01). PON1 polymorphisms may affect the ability of HDL to impede the development of atherosclerosis and to prevent inflammation.
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Effect of the human serum paraoxonase 55 and 192 genetic polymorphisms on the protection by high density lipoprotein against low density lipoprotein oxidative modification
FEBS letters, 1998Co-Authors: Bharti Mackness, Michael I Mackness, S Arrol, Wajdi Turkie, Paul N DurringtonAbstract:Human serum paraoxonase (PON1) associated with high density lipoprotein (HDL) has been postulated to have a role in protecting low density lipoprotein (LDL) against oxidative modification, which has led to the proposal that PON1 is an anti-atherogenic, anti-inflammatory enzyme. PON1 has two genetically determined polymorphic sites giving rise to amino-acid substitutions at positions 55 (L→M) and 192 (R→Q) and therefore 4 potential Alloenzymes. We have examined the effects of these molecular polymorphisms on the ability of HDL to protect LDL from oxidative modification. HDL protected LDL from oxidative modification, whatever the combination of PON1 Alloenzymes present in it. However, HDL from QQ/MM homozygotes was most effective at protecting LDL while HDL from RR/LL homozygotes was least effective. Thus after 6 h of co-incubation of HDL and LDL with Cu2+ PON1-QQ HDL retained 57±6.3% of its original ability to protect LDL from oxidative modification, while PON1-QR HDL retained less at 25.1±4.5% (P
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effect of the molecular polymorphisms of human paraoxonase pon1 on the rate of hydrolysis of paraoxon
British Journal of Pharmacology, 1997Co-Authors: Bharti Mackness, Michael I Mackness, S Arrol, Wajdi Turkie, Paul N DurringtonAbstract:1 The hydrolysis of organophosphate pesticides (OP) and nerve gases by serum paraoxonase (PON1) is an important factor determining their toxicity to mammals including man. The PON1 gene contains 2 polymorphic sites at amino acid positions 55 (LM) and 192 (GA, classically defined as the A and B genotypes) which result in several Alloenzymes of PON1 in human serum. 2 The 192 polymorphism has previously been shown to affect PON1 activity. We have investigated the effect of both polymorphisms on the hydrolysis of paraoxon by serum from 279 healthy human subjects. 3 The 55 polymorphism significantly influenced PON1 activity. MM homozygotes had over 50% less activity towards paraoxon compared to the LL and LM genotypes regardless of the 192 genotype (P<0.001). 4 Multiple regression analysis indicated that the 192 polymorphism, 55 polymorphism and serum PON1 concentration were responsible for 46, 16 and 13% of the variation in PON1 activity, respectively (all P<0.001). None of the other parameters investigated significantly affected PON1 activity. 5 Therefore both PON1 polymorphisms affect the hydrolysis of paraoxon. AA/MM and AB/MM individuals may be potentially more susceptible to OP intoxication. 6 Genotyping individuals for both PON1 polymorphisms may provide a method for identifying those individuals at most risk of OP poisoning. The effect of PON1 polymorphisms on activity may also explain why some Gulf War Veterans have developed Gulf War Syndrome and some have not. British Journal of Pharmacology (1997) 122, 265–268; doi:10.1038/sj.bjp.0701390
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Alloenzymes of paraoxonase and effectiveness of high-density lipoproteins in protecting low-density lipoprotein against lipid peroxidation.
Lancet (London England), 1997Co-Authors: Michael I Mackness, Bharti Mackness, S Arrol, Paul N DurringtonAbstract:Vol 349 • March 22, 1997 851 Our experience suggests that male-to-female transmission of HIV is infrequent during natural conception. Seroconversion occurring up to 3 months post-conception may be attributed to exposure up to the time of conception; no cases were observed. Counselling may help to reduce the risk of transmission, but this cannot be established from the number of couples followed in this study. It has been shown that there is a poor relationship between the number of acts of intercourse and the probability of transmission, indicating a great heterogeneity in infectivity. Our data may be biased being based on voluntary follow-up, and not a protocol. Some couples who did not return may have attempted to conceive unsuccessfully, and may not have reported seroconversions. Our findings are compatible with seroconversion rates in the order of 1 per 1000 episodes of unprotected intercourse reported in longitudinal studies of stable heterosexual couples, as well as in studies of transmission through artificial insemination. Some authors advocate intrauterine insemination with semen from the HIV-infected man, but the risk of this must be measured against the low background risk of natural conception. Stringent standards of safety must be required before inseminating potentially infective semen. Longitudinal virological studies are needed to evaluate whether interventions, including semen preparation, or antiretroviral therapies, can effectively clear cell-associated and cell-free virus from semen, thereby offering real hope for risk-free reproduction in “sero-different” couples.
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Effect of the molecular polymorphisms of human paraoxonase (PON1) on the rate of hydrolysis of paraoxon
British journal of pharmacology, 1997Co-Authors: Bharti Mackness, Michael I Mackness, S Arrol, Wajdi Turkie, Paul N DurringtonAbstract:1 The hydrolysis of organophosphate pesticides (OP) and nerve gases by serum paraoxonase (PON1) is an important factor determining their toxicity to mammals including man. The PON1 gene contains 2 polymorphic sites at amino acid positions 55 (LM) and 192 (GA, classically defined as the A and B genotypes) which result in several Alloenzymes of PON1 in human serum. 2 The 192 polymorphism has previously been shown to affect PON1 activity. We have investigated the effect of both polymorphisms on the hydrolysis of paraoxon by serum from 279 healthy human subjects. 3 The 55 polymorphism significantly influenced PON1 activity. MM homozygotes had over 50% less activity towards paraoxon compared to the LL and LM genotypes regardless of the 192 genotype (P
Wajdi Turkie - One of the best experts on this subject based on the ideXlab platform.
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effect of the human serum paraoxonase 55 and 192 genetic polymorphisms on the protection by high density lipoprotein against low density lipoprotein oxidative modification
FEBS Letters, 1998Co-Authors: Bharti Mackness, Michael I Mackness, S Arrol, Wajdi Turkie, Paul N DurringtonAbstract:Human serum paraoxonase (PON1) associated with high density lipoprotein (HDL) has been postulated to have a role in protecting low density lipoprotein (LDL) against oxidative modification, which has led to the proposal that PON1 is an anti-atherogenic, anti-inflammatory enzyme. PON1 has two genetically determined polymorphic sites giving rise to amino-acid substitutions at positions 55 (L→M) and 192 (R→Q) and therefore 4 potential Alloenzymes. We have examined the effects of these molecular polymorphisms on the ability of HDL to protect LDL from oxidative modification. HDL protected LDL from oxidative modification, whatever the combination of PON1 Alloenzymes present in it. However, HDL from QQ/MM homozygotes was most effective at protecting LDL while HDL from RR/LL homozygotes was least effective. Thus after 6 h of co-incubation of HDL and LDL with Cu2+ PON1-QQ HDL retained 57±6.3% of its original ability to protect LDL from oxidative modification, while PON1-QR HDL retained less at 25.1±4.5% (P<0.01) and PON1-RR HDL retained only 0.75±0.40% (P<0.005). In similar experiments HDL from LL and LM genotypes retained 21.8±7.5% and 29.5±6.6% (P=NS), respectively, of their protective ability, whereas PON1-MM HDL maintained 49.5±5.3% (P<0.01). PON1 polymorphisms may affect the ability of HDL to impede the development of atherosclerosis and to prevent inflammation.
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Effect of the human serum paraoxonase 55 and 192 genetic polymorphisms on the protection by high density lipoprotein against low density lipoprotein oxidative modification
FEBS letters, 1998Co-Authors: Bharti Mackness, Michael I Mackness, S Arrol, Wajdi Turkie, Paul N DurringtonAbstract:Human serum paraoxonase (PON1) associated with high density lipoprotein (HDL) has been postulated to have a role in protecting low density lipoprotein (LDL) against oxidative modification, which has led to the proposal that PON1 is an anti-atherogenic, anti-inflammatory enzyme. PON1 has two genetically determined polymorphic sites giving rise to amino-acid substitutions at positions 55 (L→M) and 192 (R→Q) and therefore 4 potential Alloenzymes. We have examined the effects of these molecular polymorphisms on the ability of HDL to protect LDL from oxidative modification. HDL protected LDL from oxidative modification, whatever the combination of PON1 Alloenzymes present in it. However, HDL from QQ/MM homozygotes was most effective at protecting LDL while HDL from RR/LL homozygotes was least effective. Thus after 6 h of co-incubation of HDL and LDL with Cu2+ PON1-QQ HDL retained 57±6.3% of its original ability to protect LDL from oxidative modification, while PON1-QR HDL retained less at 25.1±4.5% (P
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effect of the molecular polymorphisms of human paraoxonase pon1 on the rate of hydrolysis of paraoxon
British Journal of Pharmacology, 1997Co-Authors: Bharti Mackness, Michael I Mackness, S Arrol, Wajdi Turkie, Paul N DurringtonAbstract:1 The hydrolysis of organophosphate pesticides (OP) and nerve gases by serum paraoxonase (PON1) is an important factor determining their toxicity to mammals including man. The PON1 gene contains 2 polymorphic sites at amino acid positions 55 (LM) and 192 (GA, classically defined as the A and B genotypes) which result in several Alloenzymes of PON1 in human serum. 2 The 192 polymorphism has previously been shown to affect PON1 activity. We have investigated the effect of both polymorphisms on the hydrolysis of paraoxon by serum from 279 healthy human subjects. 3 The 55 polymorphism significantly influenced PON1 activity. MM homozygotes had over 50% less activity towards paraoxon compared to the LL and LM genotypes regardless of the 192 genotype (P<0.001). 4 Multiple regression analysis indicated that the 192 polymorphism, 55 polymorphism and serum PON1 concentration were responsible for 46, 16 and 13% of the variation in PON1 activity, respectively (all P<0.001). None of the other parameters investigated significantly affected PON1 activity. 5 Therefore both PON1 polymorphisms affect the hydrolysis of paraoxon. AA/MM and AB/MM individuals may be potentially more susceptible to OP intoxication. 6 Genotyping individuals for both PON1 polymorphisms may provide a method for identifying those individuals at most risk of OP poisoning. The effect of PON1 polymorphisms on activity may also explain why some Gulf War Veterans have developed Gulf War Syndrome and some have not. British Journal of Pharmacology (1997) 122, 265–268; doi:10.1038/sj.bjp.0701390
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Effect of the molecular polymorphisms of human paraoxonase (PON1) on the rate of hydrolysis of paraoxon
British journal of pharmacology, 1997Co-Authors: Bharti Mackness, Michael I Mackness, S Arrol, Wajdi Turkie, Paul N DurringtonAbstract:1 The hydrolysis of organophosphate pesticides (OP) and nerve gases by serum paraoxonase (PON1) is an important factor determining their toxicity to mammals including man. The PON1 gene contains 2 polymorphic sites at amino acid positions 55 (LM) and 192 (GA, classically defined as the A and B genotypes) which result in several Alloenzymes of PON1 in human serum. 2 The 192 polymorphism has previously been shown to affect PON1 activity. We have investigated the effect of both polymorphisms on the hydrolysis of paraoxon by serum from 279 healthy human subjects. 3 The 55 polymorphism significantly influenced PON1 activity. MM homozygotes had over 50% less activity towards paraoxon compared to the LL and LM genotypes regardless of the 192 genotype (P
