Dataset Information

Association of lipoprotein lipase gene polymorphisms with coronary artery disease among Filipinos.

ABSTRACT: Studies have shown association of lipoprotein lipase (LPL) polymorphisms with coronary artery disease (CAD); however, limited studies on the genetics of CAD have been done in the Philippines. Because of their effects on high-density lipoprotein and triglyceride metabolism, the G-allele of the Ser447X variant of LPL gene has been shown to be atheroprotective, while HindIII polymorphism has been shown to be pro-atherogenic. We assessed 1301 patients undergoing coronary angiography to determine the prevalence of HindIII and Ser447X polymorphisms and their association with angiographically significant CAD. Genotyping for HindIII and Ser447X variants were analyzed by real-time PCR. Multivariate analyses were performed to determine the interaction between LPL polymorphisms and risk factors of CAD. CAD+ group (72%) was predominantly male (76%) with a mean age of 60.17 ± 11.01 with hypertension (89%), dyslipidemia (84%) and smoking (54%) as the most common risk factors. HindIII carriage frequency among the CAD+ group was 20.3% with a genotypic distribution of 78.71% (T/T), 19.83% (T/G) and 1.46% (G/G). Ser447X carriage frequency among the CAD+ group was 8.0% with a genotypic distribution of 91.39% (C/C), 8.38% (C/G) and 0.23% (G/G). HindIII and Ser447X polymorphisms were both not significantly associated with CAD. LPL polymorphic allele HindIII was common, while Ser447X was rare. Present study did not show association of LPL polymorphisms with the development of CAD. However, among patients with dyslipidemia, presence of Ser447X allele is associated with an increased risk (OR 2.6; 95% CI 2.1-3.7; p value < 0.001) of developing CAD than those without LPL polymorphisms.

SUBMITTER: Gerodias FR

PROVIDER: S-EPMC6971494 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Association of lipoprotein lipase gene polymorphisms with coronary artery disease among Filipinos.

Gerodias Ferdinand R FR Posas Fabio Enrique B FEB Baclig Michael O MO Repotente Elmer Casley T ECT Pelat Jonnah Fatima B JFB Rogelio Gregorio G GG San Jose Maria Cristina Z MCZ Mapua Cynthia A CA Daroy Ma Luisa G MLG

International journal of molecular epidemiology and genetics 20191215 5

Studies have shown association of lipoprotein lipase (LPL) polymorphisms with coronary artery disease (CAD); however, limited studies on the genetics of CAD have been done in the Philippines. Because of their effects on high-density lipoprotein and triglyceride metabolism, the G-allele of the Ser447X variant of LPL gene has been shown to be atheroprotective, while <i>Hind</i>III polymorphism has been shown to be pro-atherogenic. We assessed 1301 patients undergoing coronary angiography to determ ...[more]

PMID: 31988698

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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.

Dataset Information

Association of lipoprotein lipase gene polymorphisms with coronary artery disease among Filipinos.

Publications

Association of lipoprotein lipase gene polymorphisms with coronary artery disease among Filipinos.

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