Dataset Information

Associations of three lipoprotein lipase gene polymorphisms, lipid profiles and coronary artery disease.

ABSTRACT: Lipoprotein lipase (LPL) plays a central role in lipoprotein metabolism by hydrolyzing the core triglycerides (TGs) of circulating chylomicrons and very-low-density lipoprotein (VLDL). The effects of LPL polymorphisms on lipid levels and coronary artery disease (CAD) have been inconsistent among studies and populations. To assess the lipid profiles and distributions of three LPL gene polymorphisms in Saudi patients with CAD, the HindIII, PvuII and Ser447Ter polymorphisms in the LPL gene were analyzed in 226 patients with CAD and 110 controls. Polymerase chain reaction-restriction fragment length polymorphism was used to detect LPL gene polymorphisms. The plasma lipid profiles of the patients were determined using standard enzymatic methods. Patients in the CAD group had significantly higher triglyceride (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels than controls irrespective of the HindIII, PvuII or Ser447Ter genotype. Compared to the findings in controls, the HindIII TT, PvuII TC and Ser447Ter CC genotypes were associated with significantly reduced high-density lipoprotein cholesterol (HDL-C) levels in patients with CAD (P<0.0001). In summary, there are associations between LPL gene variants and high plasma TG, TC and LDL-C levels as well as low HDL-C levels.

SUBMITTER: Daoud MS

PROVIDER: S-EPMC3917734 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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Associations of three lipoprotein lipase gene polymorphisms, lipid profiles and coronary artery disease.

Daoud Mohamed S MS Ataya Farid S FS Fouad Dalia D Alhazzani Amal A Shehata Afaf I AI Al-Jafari Abdulaziz A AA

Biomedical reports 20130530 4

Lipoprotein lipase (LPL) plays a central role in lipoprotein metabolism by hydrolyzing the core triglycerides (TGs) of circulating chylomicrons and very-low-density lipoprotein (VLDL). The effects of LPL polymorphisms on lipid levels and coronary artery disease (CAD) have been inconsistent among studies and populations. To assess the lipid profiles and distributions of three LPL gene polymorphisms in Saudi patients with CAD, the <i>Hin</i>dIII, <i>Pvu</i>II and Ser447Ter polymorphisms in the LPL ...[more]

PMID: 24648989

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Project description:ImportanceThe activity of lipoprotein lipase (LPL) is the rate-determining step in clearing triglyceride-rich lipoproteins from the circulation. Mutations that damage the LPL gene (LPL) lead to lifelong deficiency in enzymatic activity and can provide insight into the relationship of LPL to human disease.ObjectiveTo determine whether rare and/or common variants in LPL are associated with early-onset coronary artery disease (CAD).Design, setting, and participantsIn a cross-sectional study, LPL was sequenced in 10 CAD case-control cohorts of the multinational Myocardial Infarction Genetics Consortium and a nested CAD case-control cohort of the Geisinger Health System DiscovEHR cohort between 2010 and 2015. Common variants were genotyped in up to 305 699 individuals of the Global Lipids Genetics Consortium and up to 120 600 individuals of the CARDIoGRAM Exome Consortium between 2012 and 2014. Study-specific estimates were pooled via meta-analysis.ExposuresRare damaging mutations in LPL included loss-of-function variants and missense variants annotated as pathogenic in a human genetics database or predicted to be damaging by computer prediction algorithms trained to identify mutations that impair protein function. Common variants in the LPL gene region included those independently associated with circulating triglyceride levels.Main outcomes and measuresCirculating lipid levels and CAD.ResultsAmong 46 891 individuals with LPL gene sequencing data available, the mean (SD) age was 50 (12.6) years and 51% were female. A total of 188 participants (0.40%; 95% CI, 0.35%-0.46%) carried a damaging mutation in LPL, including 105 of 32 646 control participants (0.32%) and 83 of 14 245 participants with early-onset CAD (0.58%). Compared with 46 703 noncarriers, the 188 heterozygous carriers of an LPL damaging mutation displayed higher plasma triglyceride levels (19.6 mg/dL; 95% CI, 4.6-34.6 mg/dL) and higher odds of CAD (odds ratio = 1.84; 95% CI, 1.35-2.51; P < .001). An analysis of 6 common LPL variants resulted in an odds ratio for CAD of 1.51 (95% CI, 1.39-1.64; P = 1.1 × 10-22) per 1-SD increase in triglycerides.Conclusions and relevanceThe presence of rare damaging mutations in LPL was significantly associated with higher triglyceride levels and presence of coronary artery disease. However, further research is needed to assess whether there are causal mechanisms by which heterozygous lipoprotein lipase deficiency could lead to coronary artery disease.

Project description:Genetic variations that influence DNA repair efficiency may contribute to coronary artery disease (CAD) susceptibility. Previous studies have investigated whether there was evidence of an association between polymorphisms at the X-ray repair cross complementing 1 (XRCC1) gene and susceptibility to CAD, but findings have been inconclusive. We identified eligible studies through a comprehensive literature search to determine whether an association exists between XRCC1 gene polymorphisms and CAD susceptibility. Findings were assessed using the odds ratio (OR) and corresponding 95% confidence interval (CI), which were calculated using a fixed- or random-effects model, based on the heterogeneity of the studies. Ten eligible studies were finally included in this meta-analysis. Our pooled analysis found that XRCC1 polymorphisms were significantly associated with CAD susceptibility under recessive (Arg194Trp: OR = 1.47, 95% CI = 1.13-1.93; Arg399Gln: OR = 1.45, 95% CI = 1.12-1.89), homozygous (Arg194Trp: OR = 1.37, 95% CI = 1.03-1.81; Arg399Gln: OR = 1.56, 95% CI = 1.19-2.05), and allele (Arg399Gln: OR = 1.18, 95% CI = 1.06-1.32) genetic models. Following subgroup analysis by ethnicity, in Asian populations, we found evidence of associations between the XRCC1 Arg194Trp polymorphism and CAD under recessive and homozygous genetic models, and between the XRCC1 Arg399Gln polymorphism and CAD under recessive, homozygous, and allele genetic models. Subgroup analysis stratified by control source revealed associations between the Arg194Trp and Arg399Gln polymorphisms and susceptibility to CAD under recessive and homozygous modes of inheritance, respectively. In addition, subgroup analysis stratified by sample size found that findings of the Arg194Trp polymorphism in large sample sizes were comparable to those found using pooled eligible studies. Based on our meta-analysis, we concluded that the XRCC1 gene polymorphisms, Arg194Trp and Arg399Gln, are associated with CAD susceptibility, specifically in Asian populations. However, additional, comprehensive and well-designed studies are warranted to confirm these findings.

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Associations of three lipoprotein lipase gene polymorphisms, lipid profiles and coronary artery disease.

Publications

Associations of three lipoprotein lipase gene polymorphisms, lipid profiles and coronary artery disease.

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