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Andrew A. Hicks - One of the best experts on this subject based on the ideXlab platform.

  • A variant of the gene encoding leukotriene A4 hydrolase confers ethnicity-specific risk of myocardial infarction.
    Nature Genetics, 2005
    Co-Authors: Anna Helgadottir, Agnar Helgason, Daniel F. Gudbjartsson, Kristinn P. Magnusson, Gudmundur Gudmundsson, Solveig Gretarsdottir, Andrei Manolescu, Gudmar Thorleifsson, Unnur Thorsteinsdottir, Andrew A. Hicks
    Abstract:

    Variants of the gene ALOX5AP (also known as FLAP) encoding Arachidonate 5-Lipoxygenase activating protein are known to be associated with risk of myocardial infarction 1 . Here we show that a haplotype (HapK) spanning the LTA4H gene encoding leukotriene A4 hydrolase, a protein in the same biochemical pathway as ALOX5AP, confers modest risk of myocardial infarction in an Icelandic cohort. Measurements of leukotriene B4 (LTB4) production suggest that this risk is mediated through upregulation of the leukotriene pathway. Three cohorts from the United States also show that HapK confers a modest relative risk (1.16) in European Americans, but it confers a threefold larger risk in African Americans. About 27% of the European American controls carried at least one copy of HapK, as compared with only 6% of African American controls. Our analyses indicate that HapK is very rare in Africa and that its occurrence in African Americans is due to European admixture. Interactions with other genetic or environmental risk factors that are more common in African Americans are likely to account for the greater relative risk conferred by HapK in this group.

Shen Dandan - One of the best experts on this subject based on the ideXlab platform.

  • correlation of Arachidonate 5 lipoxygenase activating protein gene sg13s114t a polymorphism with acute coronary syndrome in male
    Heart, 2012
    Co-Authors: He Guoping, Hui Jingjiao, Shen Dandan
    Abstract:

    Objectives To investigate the possible association between Arachidonate 5-Lipoxygenase activating protein (ALOX5AP) gene SG13S114T/A polymorphism and acute coronary syndrome (ACS) in male. Methods A case-control study was conducted in 374 ACS patients documented by coronary angiography and 288 control subjects without coronary artery disease. The ALOX5AP gene SG13S114T/A polymorphism was determined by PCR and restruction fragment length polymorphism analysis. Results Compared with those in control group, there was no statistical difference of frequencies of AA, AT and TT genotype (p>0.05) and the T allele frequency was obviously higher (68.06% vs 82.42%, p Conclusions The AT and TT genotype and the T allele of ALOX5AP gene SG13S114T/A may be associated with the susceptibility to ACS in male.

  • relationship of Arachidonate 5 lipoxygenase activating protein gene sg13s114t a polymorphism with acute myocardial infarction
    Heart, 2012
    Co-Authors: He Guoping, Hui Jingjiao, Shen Dandan
    Abstract:

    Objectives To investigate the association between 5-Lipoxygenase activating protein (ALOX5AP) gene SG13S114T/A polymorphism and acute myocardial infarction (AMI) in the Chinese Han population of Sunan region. Methods All of 300 patients with AMI and 415 control subjects free from coronary artery disease were recruited into the study. The ALOX5AP SG13S114T/A polymorph ism gene was determined by PCR and restriction fragment length polymorphism analysis. Results (1) Compared with the control group, there was statistical difference of the frequencies of TT and AT genotype in the AMI group (p value was 0.027 and 0.032 respectively); the frequencies of T allele was not significantly different (59.50% vs 64.82%, p=0.324). (2) subgroup revealed: The frequencies of AA, AT, TT genotype and the T allele of the SG13S114T/A had no association with AMI in male group, but the frequency of TT genotype had significant correlation with AMI in female. Multivariate logistic regression analysis indicated that there was significantly correlation between ALOX5AP gene SG13S114T/A AT and TT with AMI (p value was 0.000 and 0.001 respectively). Tallele had significantly association with AMI (p=0.038). There w as statistical difference of the frequencies of AT and TT genotype with AMI in both male and female (p value was 0.010 and 0.040 respectively in male group; p value was 0.010 and 0.004 respectively in female group), Tallele was a significant risk factor for AMI in the female carrier (p=0.026), but had no association with AMI in male (p=0.285). Conclusions Conclusion: The ALOX5AP gene SG13S114T/A polymorphism may be associated with the susceptibility to AMI in the Chinese Han population of Sunan region. The T allele was a significant genetical risk factor for AMI and was the susceptibility to AMI in the female.

  • relationship of Arachidonate 5 lipoxygenase activating protein gene sg13s114t a polymorphism with the serum leukotriene b4 level in patients with acute myocardial infarction
    Heart, 2012
    Co-Authors: He Guoping, Hui Jingjiao, Shen Dandan, Ye Shan, Qi Chuanping
    Abstract:

    Objectives To investigate the association of the serum leukotrienes (LT) B4 level with the ALOX5AP gene SG13S114T/A polymorphism in patients with acute myocardial infarction (AMI) in Chinese Han population of Sunan region. Methods The ALOX5AP gene SG13S114T/A polymorphism was genotyped by PCR and restriction fragment length polymorphism analysis, and the serum LTB4 level (M/IQR) was measured by ELISA in 262 AMI patients (AMI group) and 132 subjects without coronary heart disease (CHD) (control group). Results Serum LTB4 level in AMI group was significantly higher than the one in control group (477.97/370.52 pg/ml vs 200.57/236.65 pg/ml, p 0.05), and there was also no significant difference in serum LTB4 level among any genotypes in this locus within the same gender (p>0.05). The serum LTB4 level was positively correlated with the smoking, and unrelated with the gender, age, hypertension, diabetes and hyperlipidaemia in AMI patients. Conclusions In Chinese Han population of Sunan region, there are polymorphisms of ALOX5AP gene SG13S114 in patients with AMI and subjects without CHD. The serum LTB4 level in AMI patients is higher than those in subjects without CHD, but unrelated with ALOX5AP gene SG13S114 polymorphism.

  • Arachidonate 5 lipoxygenase activating protein gene sg13s114t a polymorphism and the susceptibility to acute coronary syndrome
    Chinese Journal of Geriatric Heart Brain and Vessel Diseases, 2011
    Co-Authors: Shen Dandan
    Abstract:

    Objective To investigate the possible association of Arachidonate 5-Lipoxygenase activating protein(ALOX5AP)gene SG13S114T/A polymorphism with the susceptibility to acute coronary syndrome(ACS).Methods 714 in-patients with chest pain were chosen and were divided into ACS group(377 cases with ACS) and control group(337 subjects without ACS).The ALOX5AP gene SG13S114T/A polymorphism was determined by polymerase chain reaction and restriction fragment length polymorphism analysis,and multiple logistic regression analysis was performed.Results Genotype frequencies of ALOX5AP gene SG13S114T/A AA,AT and TT were 13.79%,50.93%and 35.28%respectively in patients of ACS group and 12.76%,38.58% and 48.66%respectively in control subjects.Compared with control group,there was statistical difference in frequencies of AT and TT genotypes in ACS group(P = 0.041,0.020).The AT genotype frequency in male ACS group was obeviously higher(40.7%vs 52.5%,P = 0.040) and the TT genotype frequency in female ACS group was significantly lower(61.8%vs 37.0%,P = 0.013) than control group.The frequencies of AT,TT genotypes and the T allele were related with attack of ACS(P = 0.004,0.001 and 0.013,respectively) and male ACS(P = 0.014,0.005 and 0.020,respectively).Conclusion The AT and TT genotypes and the T allele of ALOX5AP gene SG13S114T/A polymorphism may be associated with the susceptibility to ACS in the elderly, especially in the aged males.

He Guoping - One of the best experts on this subject based on the ideXlab platform.

  • correlation of Arachidonate 5 lipoxygenase activating protein gene sg13s114t a polymorphism with acute coronary syndrome in male
    Heart, 2012
    Co-Authors: He Guoping, Hui Jingjiao, Shen Dandan
    Abstract:

    Objectives To investigate the possible association between Arachidonate 5-Lipoxygenase activating protein (ALOX5AP) gene SG13S114T/A polymorphism and acute coronary syndrome (ACS) in male. Methods A case-control study was conducted in 374 ACS patients documented by coronary angiography and 288 control subjects without coronary artery disease. The ALOX5AP gene SG13S114T/A polymorphism was determined by PCR and restruction fragment length polymorphism analysis. Results Compared with those in control group, there was no statistical difference of frequencies of AA, AT and TT genotype (p>0.05) and the T allele frequency was obviously higher (68.06% vs 82.42%, p Conclusions The AT and TT genotype and the T allele of ALOX5AP gene SG13S114T/A may be associated with the susceptibility to ACS in male.

  • interrelation among the serum leukotriene b4 level Arachidonate 5 lipoxygenase activating protein gene sg13s89g a polymorphism and risk of acute myocardial infarction
    Heart, 2012
    Co-Authors: He Guoping, Hui Jingjiao, Ye Shan, Qi Chuanping
    Abstract:

    Objectives To investigate the interrelation among the serum leukotriene (LT) B4 level, the Arachidonate 5-Lipoxygenase activating protein (ALOX5AP) gene SG13S89G/A polymorphism and the risk of acute myocardial infarction (AMI) in the Chinese Han population of Changzhou region. Methods The polymorphism in the ALOX5AP gene SG13S89G/A was genotyped by PCR and restriction fragment length polymorphism analysis and the serum LTB4 level (M/IQR) was measured by ELISA in 262 patients with AMI (AMI group) and 132 subjects with chest pain who were free from coronary heart disease by coronarography (control group). Results As compared with those in control group, there were no significant differences in (AA+GA) and GG genetype (7.58% vs 4.96% and 92.42% vs 95.04%, respectively), and A allele frequencie (4.17% vs 2.67%) of ALOX5AP gene SG13S89G/A locus in AMI group (all the p value >0.05). Multivariable logistic regression analysis showed that there was no significant association between ALOX5AP gene SG13S89G/A polymorphism and the risk of AMI. The serum LTB4 level in AMI group was significantly higher than the one in control group (477.97/370.52 pg/ml vs 200.57/236.65 pg/ml, p 0.05). Conclusions The serum LTB4 level is significantly increased in patients with AMI; the ALOX5AP gene SG13S114G/A polymorphism may not be correlated to the risk of AMI and not influence the serum LTB4 level in Chinese Han population of Changzhou region.

  • relationship of Arachidonate 5 lipoxygenase activating protein gene sg13s114t a polymorphism with acute myocardial infarction
    Heart, 2012
    Co-Authors: He Guoping, Hui Jingjiao, Shen Dandan
    Abstract:

    Objectives To investigate the association between 5-Lipoxygenase activating protein (ALOX5AP) gene SG13S114T/A polymorphism and acute myocardial infarction (AMI) in the Chinese Han population of Sunan region. Methods All of 300 patients with AMI and 415 control subjects free from coronary artery disease were recruited into the study. The ALOX5AP SG13S114T/A polymorph ism gene was determined by PCR and restriction fragment length polymorphism analysis. Results (1) Compared with the control group, there was statistical difference of the frequencies of TT and AT genotype in the AMI group (p value was 0.027 and 0.032 respectively); the frequencies of T allele was not significantly different (59.50% vs 64.82%, p=0.324). (2) subgroup revealed: The frequencies of AA, AT, TT genotype and the T allele of the SG13S114T/A had no association with AMI in male group, but the frequency of TT genotype had significant correlation with AMI in female. Multivariate logistic regression analysis indicated that there was significantly correlation between ALOX5AP gene SG13S114T/A AT and TT with AMI (p value was 0.000 and 0.001 respectively). Tallele had significantly association with AMI (p=0.038). There w as statistical difference of the frequencies of AT and TT genotype with AMI in both male and female (p value was 0.010 and 0.040 respectively in male group; p value was 0.010 and 0.004 respectively in female group), Tallele was a significant risk factor for AMI in the female carrier (p=0.026), but had no association with AMI in male (p=0.285). Conclusions Conclusion: The ALOX5AP gene SG13S114T/A polymorphism may be associated with the susceptibility to AMI in the Chinese Han population of Sunan region. The T allele was a significant genetical risk factor for AMI and was the susceptibility to AMI in the female.

  • relationship of Arachidonate 5 lipoxygenase activating protein gene sg13s114t a polymorphism with the serum leukotriene b4 level in patients with acute myocardial infarction
    Heart, 2012
    Co-Authors: He Guoping, Hui Jingjiao, Shen Dandan, Ye Shan, Qi Chuanping
    Abstract:

    Objectives To investigate the association of the serum leukotrienes (LT) B4 level with the ALOX5AP gene SG13S114T/A polymorphism in patients with acute myocardial infarction (AMI) in Chinese Han population of Sunan region. Methods The ALOX5AP gene SG13S114T/A polymorphism was genotyped by PCR and restriction fragment length polymorphism analysis, and the serum LTB4 level (M/IQR) was measured by ELISA in 262 AMI patients (AMI group) and 132 subjects without coronary heart disease (CHD) (control group). Results Serum LTB4 level in AMI group was significantly higher than the one in control group (477.97/370.52 pg/ml vs 200.57/236.65 pg/ml, p 0.05), and there was also no significant difference in serum LTB4 level among any genotypes in this locus within the same gender (p>0.05). The serum LTB4 level was positively correlated with the smoking, and unrelated with the gender, age, hypertension, diabetes and hyperlipidaemia in AMI patients. Conclusions In Chinese Han population of Sunan region, there are polymorphisms of ALOX5AP gene SG13S114 in patients with AMI and subjects without CHD. The serum LTB4 level in AMI patients is higher than those in subjects without CHD, but unrelated with ALOX5AP gene SG13S114 polymorphism.

Jagadananda Ghosh - One of the best experts on this subject based on the ideXlab platform.

  • oxer1 a g protein coupled oxoeicosatetraenoid receptor mediates the survival promoting effects of Arachidonate 5 lipoxygenase in prostate cancer cells
    Cancer Letters, 2013
    Co-Authors: Sivalokanathan Sarveswaran, Jagadananda Ghosh
    Abstract:

    Inhibition of 5-Lox induces apoptosis in prostate cancer cells by inactivating PKCe which is prevented by 5-oxoETE, and activators of PKCe prevent 5-Lox inhibition-induced apoptosis, suggesting that 5-Lox metabolites exert survival signaling via PKCe. However, mechanisms by which 5-Lox metabolites activate PKCe are not understood yet. We found that prostate cancer cells express high levels of OXER1, a G protein-coupled 5-oxoETE receptor, which delivers signal by generating diacyl-glycerol through phospholipase C-beta. Interestingly, we found that U73122, an inhibitor of PLC-beta, interrupts the apoptosis-preventing effect of 5-oxoETE, and exogenous diacyl-glycerol effectively prevents 5-Lox inhibition-induced apoptosis, suggesting that 5-oxoETE signals via OXER1 to promote prostate cancer cell survival.

  • Rapid induction of apoptosis in prostate cancer cells by selenium: reversal by metabolites of Arachidonate 5-Lipoxygenase.
    Biochemical and biophysical research communications, 2004
    Co-Authors: Jagadananda Ghosh
    Abstract:

    Recent clinical trials have documented that selenium significantly reduces the incidence of clinical prostate cancer. However, nothing is clearly known about the underlying molecular mechanisms by which selenium exerts its anti-cancer effect. This report provides evidence that selenium at micro-molar concentrations induces rapid apoptotic death in human prostate cancer cells, but not in normal prostate epithelial cells. Apoptosis involves activation of caspase 3 which plays a critical role in the cell death process. Interestingly, the apoptosis-inducing effect of selenium in prostate cancer cells is substantially alleviated by the 5-Lipoxygenase metabolites, 5(S)-HETE and its dehydrogenated derivative 5-oxoETE, but not by metabolites of 12-lipoxygenase (12(S)-HETE) or 15-Lipoxygenase (15(S)-HETE). Apoptosis is also prevented by their precursor, arachidonic acid, an omega-6, polyunsaturated fatty acid, presumably by metabolic conversion through the 5-Lipoxygenase pathway. These results indicate that selenium's anticancer effect may involve induction of apoptosis specifically in prostate cancer cells sparing normal prostate epithelial cells, and that 5-Lipoxygenase may be a molecular target of selenium's anticancer action. The present report warrants that care should be taken about high intake of dietary fat containing arachidonic acid or its precursor fatty acids when selenium is used for the management of prostate cancer, and suggests that a combination of selenium and 5-Lipoxygenase inhibitors may be a more effective regimen for prostate cancer control.

  • molecular mechanisms of prostate cancer cell death triggered by inhibition of Arachidonate 5 lipoxygenase involvement of fas death receptor mediated signals
    Advances in Experimental Medicine and Biology, 2002
    Co-Authors: Jagadananda Ghosh, Charles E Myers
    Abstract:

    Cancer is the result of uncontrolled cell proliferation and has emerged as one of the most frequently diagnosed challenges to human health all over the world. While formation of new cells is an integral part of cancer biology, decreased death of tumor cells has recently emerged as a focus of attention as the leading cause of deregulated tissue homeostasis resulting in cancer-related tumor burden. The cell loss factor is the major determinant of tumor growth rate with values approaching to as high as 90% in some case (1). Chemotherapeutic drugs are designed to reverse the order of cancer cell behavior by blocking cell division and/or increasing cell death. Apoptosis, or programmed cell death, is a genetically based suicide mechanism preserved through evolutionary ages (2), by which infected and damaged cells are selectively eliminated from the body in a controlled fashion without much inflammatory or bystander effects. It is the dominant mechanism of cell death in multicellular species. Drugs currently in use for cancer chemotherapy, in most cases, work by induction of apoptosis, either through membrane-localized cell death receptor-mediated signals or by the involvement of mitochondria. Other cancer-therapeutic modalities including radiotherapy, immunotherapy and hormone ablation also induce cell death by apoptosis. Tumor cells, on the other hand, are posing a threat of drug-resistance by deregulating the cell-death program (“drug neo-resistance”) or immuno-resistance by expressing cell death signal-inducing ligands on their surface to counterattack the antitumor lymphocytes.

  • inhibition of Arachidonate 5 lipoxygenase triggers massive apoptosis in human prostate cancer cells
    Proceedings of the National Academy of Sciences of the United States of America, 1998
    Co-Authors: Jagadananda Ghosh, Charles E Myers
    Abstract:

    Diets high in fat are associated with an increased risk of prostate cancer, although the molecular mechanism is still unknown. We have previously reported that arachidonic acid, an omega-6 fatty acid common in the Western diet, stimulates proliferation of prostate cancer cells through production of the 5-Lipoxygenase metabolite, 5-HETE (5-hydroxyeicosatetraenoic acid). We now show that 5-HETE is also a potent survival factor for human prostate cancer cells. These cells constitutively produce 5-HETE in serum-free medium with no added stimulus. Exogenous Arachidonate markedly increases the production of 5-HETE. Inhibition of 5-Lipoxygenase by MK886 completely blocks 5-HETE production and induces massive apoptosis in both hormone-responsive (LNCaP) and -nonresponsive (PC3) human prostate cancer cells. This cell death is very rapid: cells treated with MK886 showed mitochondrial permeability transition between 30 and 60 min, externalization of phosphatidylserine within 2 hr, and degradation of DNA to nucleosomal subunits beginning within 2–4 hr posttreatment. Cell death was effectively blocked by the thiol antioxidant, N-acetyl-l-cysteine, but not by androgen, a powerful survival factor for prostate cancer cells. Apoptosis was specific for 5-Lipoxygenase—programmed cell death was not observed with inhibitors of 12-lipoxygenase, cyclooxygenase, or cytochrome P450 pathways of arachidonic acid metabolism. Exogenous 5-HETE protects these cells from apoptosis induced by 5-Lipoxygenase inhibitors, confirming a critical role of 5-Lipoxygenase activity in the survival of these cells. These findings provide a possible molecular mechanism by which dietary fat may influence the progression of prostate cancer.

Anna Helgadottir - One of the best experts on this subject based on the ideXlab platform.

  • A variant of the gene encoding leukotriene A4 hydrolase confers ethnicity-specific risk of myocardial infarction.
    Nature Genetics, 2005
    Co-Authors: Anna Helgadottir, Agnar Helgason, Daniel F. Gudbjartsson, Kristinn P. Magnusson, Gudmundur Gudmundsson, Solveig Gretarsdottir, Andrei Manolescu, Gudmar Thorleifsson, Unnur Thorsteinsdottir, Andrew A. Hicks
    Abstract:

    Variants of the gene ALOX5AP (also known as FLAP) encoding Arachidonate 5-Lipoxygenase activating protein are known to be associated with risk of myocardial infarction 1 . Here we show that a haplotype (HapK) spanning the LTA4H gene encoding leukotriene A4 hydrolase, a protein in the same biochemical pathway as ALOX5AP, confers modest risk of myocardial infarction in an Icelandic cohort. Measurements of leukotriene B4 (LTB4) production suggest that this risk is mediated through upregulation of the leukotriene pathway. Three cohorts from the United States also show that HapK confers a modest relative risk (1.16) in European Americans, but it confers a threefold larger risk in African Americans. About 27% of the European American controls carried at least one copy of HapK, as compared with only 6% of African American controls. Our analyses indicate that HapK is very rare in Africa and that its occurrence in African Americans is due to European admixture. Interactions with other genetic or environmental risk factors that are more common in African Americans are likely to account for the greater relative risk conferred by HapK in this group.