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Michel Marcil - One of the best experts on this subject based on the ideXlab platform.

  • Sphingomyelin Phosphodiesterase 1 smpd1 coding variants do not contribute to low levels of high density lipoprotein cholesterol
    BMC Medical Genetics, 2007
    Co-Authors: Zari Dastani, Isabelle Ruel, James C Engert, Jacques Genest, Michel Marcil
    Abstract:

    Niemann-Pick disease type A and B is caused by a deficiency of acid Sphingomyelinase due to mutations in the Sphingomyelin Phosphodiesterase-1 (SMPD1) gene. In Niemann-Pick patients, SMPD1 gene defects are reported to be associated with a severe reduction in plasma high-density lipoprotein (HDL) cholesterol. Two common coding polymorphisms in the SMPD1 gene, the G1522A (G508R) and a hexanucleotide repeat sequence within the signal peptide region, were investigated in 118 unrelated subjects of French Canadian descent with low plasma levels of HDL-cholesterol ( the 25th percentile. For G1522A the frequency of the G and A alleles were 75.2% and 24.8% respectively in controls, compared to 78.6% and 21.4% in subjects with low HDL-cholesterol (p = 0.317). The frequency of 6 and 7 hexanucleotide repeats was 46.2% and 46.6% respectively in controls, compared to 45.6% and 49.1% in subjects with low HDL-cholesterol (p = 0.619). Ten different haplotypes were observed in cases and controls. Overall haplotype frequencies in cases and controls were not significantly different. These results suggest that the two common coding variants at the SMPD1 gene locus are not associated with low HDL-cholesterol levels in the French Canadian population.

  • Sphingomyelin Phosphodiesterase-1 (SMPD1) coding variants do not contribute to low levels of high-density lipoprotein cholesterol
    BMC Medical Genetics, 2007
    Co-Authors: Zari Dastani, James C Engert, Jacques Genest, Isabelle L Ruel, Michel Marcil
    Abstract:

    Background Niemann-Pick disease type A and B is caused by a deficiency of acid Sphingomyelinase due to mutations in the Sphingomyelin Phosphodiesterase-1 ( SMPD1 ) gene. In Niemann-Pick patients, SMPD1 gene defects are reported to be associated with a severe reduction in plasma high-density lipoprotein (HDL) cholesterol. Methods Two common coding polymorphisms in the SMPD1 gene, the G1522A (G508R) and a hexanucleotide repeat sequence within the signal peptide region, were investigated in 118 unrelated subjects of French Canadian descent with low plasma levels of HDL-cholesterol (< 5^th percentile for age and gender-matched subjects). Control subjects (n = 230) had an HDL-cholesterol level > the 25^th percentile. Results For G1522A the frequency of the G and A alleles were 75.2% and 24.8% respectively in controls, compared to 78.6% and 21.4% in subjects with low HDL-cholesterol ( p = 0.317). The frequency of 6 and 7 hexanucleotide repeats was 46.2% and 46.6% respectively in controls, compared to 45.6% and 49.1% in subjects with low HDL-cholesterol ( p = 0.619). Ten different haplotypes were observed in cases and controls. Overall haplotype frequencies in cases and controls were not significantly different. Conclusion These results suggest that the two common coding variants at the SMPD1 gene locus are not associated with low HDL-cholesterol levels in the French Canadian population.

  • compound heterozygosity at the Sphingomyelin Phosphodiesterase 1 smpd1 gene is associated with low hdl cholesterol
    Human Genetics, 2003
    Co-Authors: Jacques Genest, Michel Marcil, Ching Yin Lee, Larbi Krimbou, Jerome Vincent, Chantal Bernard, Pierre Larramee
    Abstract:

    Type A and B forms of Niemann-Pick disease (NPD) are lipid storage disorders caused by deficient activity of the enzyme acid Sphingomyelinase (aSMase) and the resulting accumulation of Sphingomyelin in tissues. In the present study, we investigated two family members who had been diagnosed with Type B NPD and who had a severe decrease in plasma high density lipoprotein cholesterol (HDL-C). The proband (a 48-year-old male) had an HDL-C of 0.30 mmol/l (12 mg/dl) and his sister had values of 0.45 mmol/l (17 mg/dl) with severe premature coronary artery disease (CAD). Hypertriglyceridemia was found in both cases. aSMase activity measured in skin fibroblasts appeared markedly depressed. The SMPD1 gene, coding for aSMase, was sequenced in affected subjects and all family members. Compound heterozygosity (DeltaR608 and R441X) was identified in both affected patients. Carriers of the DeltaR608 mutation tended to have moderately to severe decreased HDL-C levels, whereas carriers of the R441X mutation, although present only in young subjects (<20 years of age) had normal HDL-C levels. To investigate the cause of the low HDL-C level in these patients, we studied apoA-I-mediated cellular cholesterol efflux in fibroblasts. Unlike patients with Tangier disease, cholesterol efflux was found to be normal under the experimental conditions used in the present study. On the other hand, we observed a significant increase in the free cholesterol:esterified cholesterol ratio in HDL fraction from these patients and a decrease in endogenous lecithin-cholesterol acyltransferase (LCAT) activity, as determined by the fractional esterification rate. Taken together, these results suggest that (1) compound heterozygosity at the SMPD1 gene causes a severe decrease in aSMase activity and in HDL-C and increases the risk of CAD, (2) this lipoprotein abnormality is not attributable to defective cellular cholesterol efflux, (3) abnormal HDL composition might cause a decrease in LCAT activity and a lack of HDL maturation.

Jacques Genest - One of the best experts on this subject based on the ideXlab platform.

  • Sphingomyelin Phosphodiesterase 1 smpd1 coding variants do not contribute to low levels of high density lipoprotein cholesterol
    BMC Medical Genetics, 2007
    Co-Authors: Zari Dastani, Isabelle Ruel, James C Engert, Jacques Genest, Michel Marcil
    Abstract:

    Niemann-Pick disease type A and B is caused by a deficiency of acid Sphingomyelinase due to mutations in the Sphingomyelin Phosphodiesterase-1 (SMPD1) gene. In Niemann-Pick patients, SMPD1 gene defects are reported to be associated with a severe reduction in plasma high-density lipoprotein (HDL) cholesterol. Two common coding polymorphisms in the SMPD1 gene, the G1522A (G508R) and a hexanucleotide repeat sequence within the signal peptide region, were investigated in 118 unrelated subjects of French Canadian descent with low plasma levels of HDL-cholesterol ( the 25th percentile. For G1522A the frequency of the G and A alleles were 75.2% and 24.8% respectively in controls, compared to 78.6% and 21.4% in subjects with low HDL-cholesterol (p = 0.317). The frequency of 6 and 7 hexanucleotide repeats was 46.2% and 46.6% respectively in controls, compared to 45.6% and 49.1% in subjects with low HDL-cholesterol (p = 0.619). Ten different haplotypes were observed in cases and controls. Overall haplotype frequencies in cases and controls were not significantly different. These results suggest that the two common coding variants at the SMPD1 gene locus are not associated with low HDL-cholesterol levels in the French Canadian population.

  • Sphingomyelin Phosphodiesterase-1 (SMPD1) coding variants do not contribute to low levels of high-density lipoprotein cholesterol
    BMC Medical Genetics, 2007
    Co-Authors: Zari Dastani, James C Engert, Jacques Genest, Isabelle L Ruel, Michel Marcil
    Abstract:

    Background Niemann-Pick disease type A and B is caused by a deficiency of acid Sphingomyelinase due to mutations in the Sphingomyelin Phosphodiesterase-1 ( SMPD1 ) gene. In Niemann-Pick patients, SMPD1 gene defects are reported to be associated with a severe reduction in plasma high-density lipoprotein (HDL) cholesterol. Methods Two common coding polymorphisms in the SMPD1 gene, the G1522A (G508R) and a hexanucleotide repeat sequence within the signal peptide region, were investigated in 118 unrelated subjects of French Canadian descent with low plasma levels of HDL-cholesterol (< 5^th percentile for age and gender-matched subjects). Control subjects (n = 230) had an HDL-cholesterol level > the 25^th percentile. Results For G1522A the frequency of the G and A alleles were 75.2% and 24.8% respectively in controls, compared to 78.6% and 21.4% in subjects with low HDL-cholesterol ( p = 0.317). The frequency of 6 and 7 hexanucleotide repeats was 46.2% and 46.6% respectively in controls, compared to 45.6% and 49.1% in subjects with low HDL-cholesterol ( p = 0.619). Ten different haplotypes were observed in cases and controls. Overall haplotype frequencies in cases and controls were not significantly different. Conclusion These results suggest that the two common coding variants at the SMPD1 gene locus are not associated with low HDL-cholesterol levels in the French Canadian population.

  • compound heterozygosity at the Sphingomyelin Phosphodiesterase 1 smpd1 gene is associated with low hdl cholesterol
    Human Genetics, 2003
    Co-Authors: Jacques Genest, Michel Marcil, Ching Yin Lee, Larbi Krimbou, Jerome Vincent, Chantal Bernard, Pierre Larramee
    Abstract:

    Type A and B forms of Niemann-Pick disease (NPD) are lipid storage disorders caused by deficient activity of the enzyme acid Sphingomyelinase (aSMase) and the resulting accumulation of Sphingomyelin in tissues. In the present study, we investigated two family members who had been diagnosed with Type B NPD and who had a severe decrease in plasma high density lipoprotein cholesterol (HDL-C). The proband (a 48-year-old male) had an HDL-C of 0.30 mmol/l (12 mg/dl) and his sister had values of 0.45 mmol/l (17 mg/dl) with severe premature coronary artery disease (CAD). Hypertriglyceridemia was found in both cases. aSMase activity measured in skin fibroblasts appeared markedly depressed. The SMPD1 gene, coding for aSMase, was sequenced in affected subjects and all family members. Compound heterozygosity (DeltaR608 and R441X) was identified in both affected patients. Carriers of the DeltaR608 mutation tended to have moderately to severe decreased HDL-C levels, whereas carriers of the R441X mutation, although present only in young subjects (<20 years of age) had normal HDL-C levels. To investigate the cause of the low HDL-C level in these patients, we studied apoA-I-mediated cellular cholesterol efflux in fibroblasts. Unlike patients with Tangier disease, cholesterol efflux was found to be normal under the experimental conditions used in the present study. On the other hand, we observed a significant increase in the free cholesterol:esterified cholesterol ratio in HDL fraction from these patients and a decrease in endogenous lecithin-cholesterol acyltransferase (LCAT) activity, as determined by the fractional esterification rate. Taken together, these results suggest that (1) compound heterozygosity at the SMPD1 gene causes a severe decrease in aSMase activity and in HDL-C and increases the risk of CAD, (2) this lipoprotein abnormality is not attributable to defective cellular cholesterol efflux, (3) abnormal HDL composition might cause a decrease in LCAT activity and a lack of HDL maturation.

Zari Dastani - One of the best experts on this subject based on the ideXlab platform.

  • Sphingomyelin Phosphodiesterase 1 smpd1 coding variants do not contribute to low levels of high density lipoprotein cholesterol
    BMC Medical Genetics, 2007
    Co-Authors: Zari Dastani, Isabelle Ruel, James C Engert, Jacques Genest, Michel Marcil
    Abstract:

    Niemann-Pick disease type A and B is caused by a deficiency of acid Sphingomyelinase due to mutations in the Sphingomyelin Phosphodiesterase-1 (SMPD1) gene. In Niemann-Pick patients, SMPD1 gene defects are reported to be associated with a severe reduction in plasma high-density lipoprotein (HDL) cholesterol. Two common coding polymorphisms in the SMPD1 gene, the G1522A (G508R) and a hexanucleotide repeat sequence within the signal peptide region, were investigated in 118 unrelated subjects of French Canadian descent with low plasma levels of HDL-cholesterol ( the 25th percentile. For G1522A the frequency of the G and A alleles were 75.2% and 24.8% respectively in controls, compared to 78.6% and 21.4% in subjects with low HDL-cholesterol (p = 0.317). The frequency of 6 and 7 hexanucleotide repeats was 46.2% and 46.6% respectively in controls, compared to 45.6% and 49.1% in subjects with low HDL-cholesterol (p = 0.619). Ten different haplotypes were observed in cases and controls. Overall haplotype frequencies in cases and controls were not significantly different. These results suggest that the two common coding variants at the SMPD1 gene locus are not associated with low HDL-cholesterol levels in the French Canadian population.

  • Sphingomyelin Phosphodiesterase-1 (SMPD1) coding variants do not contribute to low levels of high-density lipoprotein cholesterol
    BMC Medical Genetics, 2007
    Co-Authors: Zari Dastani, James C Engert, Jacques Genest, Isabelle L Ruel, Michel Marcil
    Abstract:

    Background Niemann-Pick disease type A and B is caused by a deficiency of acid Sphingomyelinase due to mutations in the Sphingomyelin Phosphodiesterase-1 ( SMPD1 ) gene. In Niemann-Pick patients, SMPD1 gene defects are reported to be associated with a severe reduction in plasma high-density lipoprotein (HDL) cholesterol. Methods Two common coding polymorphisms in the SMPD1 gene, the G1522A (G508R) and a hexanucleotide repeat sequence within the signal peptide region, were investigated in 118 unrelated subjects of French Canadian descent with low plasma levels of HDL-cholesterol (< 5^th percentile for age and gender-matched subjects). Control subjects (n = 230) had an HDL-cholesterol level > the 25^th percentile. Results For G1522A the frequency of the G and A alleles were 75.2% and 24.8% respectively in controls, compared to 78.6% and 21.4% in subjects with low HDL-cholesterol ( p = 0.317). The frequency of 6 and 7 hexanucleotide repeats was 46.2% and 46.6% respectively in controls, compared to 45.6% and 49.1% in subjects with low HDL-cholesterol ( p = 0.619). Ten different haplotypes were observed in cases and controls. Overall haplotype frequencies in cases and controls were not significantly different. Conclusion These results suggest that the two common coding variants at the SMPD1 gene locus are not associated with low HDL-cholesterol levels in the French Canadian population.

James C Engert - One of the best experts on this subject based on the ideXlab platform.

  • Sphingomyelin Phosphodiesterase 1 smpd1 coding variants do not contribute to low levels of high density lipoprotein cholesterol
    BMC Medical Genetics, 2007
    Co-Authors: Zari Dastani, Isabelle Ruel, James C Engert, Jacques Genest, Michel Marcil
    Abstract:

    Niemann-Pick disease type A and B is caused by a deficiency of acid Sphingomyelinase due to mutations in the Sphingomyelin Phosphodiesterase-1 (SMPD1) gene. In Niemann-Pick patients, SMPD1 gene defects are reported to be associated with a severe reduction in plasma high-density lipoprotein (HDL) cholesterol. Two common coding polymorphisms in the SMPD1 gene, the G1522A (G508R) and a hexanucleotide repeat sequence within the signal peptide region, were investigated in 118 unrelated subjects of French Canadian descent with low plasma levels of HDL-cholesterol ( the 25th percentile. For G1522A the frequency of the G and A alleles were 75.2% and 24.8% respectively in controls, compared to 78.6% and 21.4% in subjects with low HDL-cholesterol (p = 0.317). The frequency of 6 and 7 hexanucleotide repeats was 46.2% and 46.6% respectively in controls, compared to 45.6% and 49.1% in subjects with low HDL-cholesterol (p = 0.619). Ten different haplotypes were observed in cases and controls. Overall haplotype frequencies in cases and controls were not significantly different. These results suggest that the two common coding variants at the SMPD1 gene locus are not associated with low HDL-cholesterol levels in the French Canadian population.

  • Sphingomyelin Phosphodiesterase-1 (SMPD1) coding variants do not contribute to low levels of high-density lipoprotein cholesterol
    BMC Medical Genetics, 2007
    Co-Authors: Zari Dastani, James C Engert, Jacques Genest, Isabelle L Ruel, Michel Marcil
    Abstract:

    Background Niemann-Pick disease type A and B is caused by a deficiency of acid Sphingomyelinase due to mutations in the Sphingomyelin Phosphodiesterase-1 ( SMPD1 ) gene. In Niemann-Pick patients, SMPD1 gene defects are reported to be associated with a severe reduction in plasma high-density lipoprotein (HDL) cholesterol. Methods Two common coding polymorphisms in the SMPD1 gene, the G1522A (G508R) and a hexanucleotide repeat sequence within the signal peptide region, were investigated in 118 unrelated subjects of French Canadian descent with low plasma levels of HDL-cholesterol (< 5^th percentile for age and gender-matched subjects). Control subjects (n = 230) had an HDL-cholesterol level > the 25^th percentile. Results For G1522A the frequency of the G and A alleles were 75.2% and 24.8% respectively in controls, compared to 78.6% and 21.4% in subjects with low HDL-cholesterol ( p = 0.317). The frequency of 6 and 7 hexanucleotide repeats was 46.2% and 46.6% respectively in controls, compared to 45.6% and 49.1% in subjects with low HDL-cholesterol ( p = 0.619). Ten different haplotypes were observed in cases and controls. Overall haplotype frequencies in cases and controls were not significantly different. Conclusion These results suggest that the two common coding variants at the SMPD1 gene locus are not associated with low HDL-cholesterol levels in the French Canadian population.

Uladzislau Rudakou - One of the best experts on this subject based on the ideXlab platform.

  • smpd1 variants do not have a major role in rapid eye movement sleep behavior disorder
    Neurobiology of Aging, 2020
    Co-Authors: Jennifer Ruskey, Uladzislau Rudakou, Naomi C Futhey, Lynne Krohn, Karl Heilbron, Paul Cannon, Armaghan Alam
    Abstract:

    Abstract Mutations in the Sphingomyelin Phosphodiesterase 1 (SMPD1) gene were reported to be associated with Parkinson’s disease and dementia with Lewy bodies. In the current study, we aimed to evaluate the role of SMPD1 variants in isolated rapid eye movement sleep behavior disorder (iRBD). SMPD1 and its untranslated regions were sequenced using targeted next-generation sequencing in 959 iRBD patients and 1287 controls from European descent. Our study reports no statistically significant association of SMPD1 variants and iRBD. It is hence unlikely that SMPD1 plays a major role in iRBD.

  • smpd1 variants do not have a major role in rem sleep behavior disorder
    medRxiv, 2020
    Co-Authors: Uladzislau Rudakou, Isabelle Arnulf, Jacques Montplaisir, Jennifer Ruskey, Naomi C Futhey, Lynne Krohn, Karl Heilbron, Paul Cannon, Armaghan Alam, Jean-françois Gagnon
    Abstract:

    Mutations in the Sphingomyelin Phosphodiesterase 1 (SMPD1) gene were reported to be associated with Parkinson disease (PD) and dementia with Lewy bodies (DLB). The majority of patients with isolated rapid eye movement sleep behavior disorder (iRBD) develop PD or DLB later in life, suggesting that iRBD is a prodromal phase of these two conditions. In the current study we aimed to evaluate the role of SMPD1 variants in iRBD. SMPD1 and its untranslated regions were sequenced using targeted next-generation sequencing in 959 iRBD patients and 1,287 controls from European descent. Logistic regression adjusted for sex and age showed no significant associations with two common variants and iRBD (rs1050239 and rs8164). The frequency of all rare nonsynonymous SMPD1 variants (minor allele frequency <1%) was found to be twice as high in cases than in controls (1.46% vs. 0.70%, Fisher's exact test p=0.09) but there was no statistically significant burden (p=0.64). Our study reports no statistically significant association of SMPD1 variants and iRBD. It is hence unlikely that SMPD1 plays a major role in iRBD.