A Genetic Polymorphism in GCKR may be Associated with Low High-Density Lipoprotein Cholesterol Phenotype among Filipinos: A Case-Control Study

Background. Low levels of high-density lipoprotein cholesterol (HDL-c) is a well-recognized risk factor in the development of cardiovascular diseases. Associated gene variants for low HDL-c have already been demonstrated in various populations. Such associations have yet to be established among Filipinos who reportedly have a much higher prevalence of low HDL-c levels compared to other races. Objective. To determine the association of selected genetic variants and clinical factors with low HDL-c phenotype in Filipinos. Methods. An age- and sex-matched case-control study was conducted among adult Filipino participants with serum HDL-c concentration less than 35 mg/dL (n=61) and those with HDL-c levels of more than 40 mg/dL (n=116). Genotyping was done using DNA obtained from blood samples. Candidate variants were correlated with the low HDL-c phenotype using chi-squared test and conditional logistic regression analysis. Results. Twelve single nucleotide polymorphisms (SNPs) were associated with low HDL-c phenotype among Filipinos with univariate regression analysis. The variant rs1260326 of glucokinase regulator (GCKR) (CT genotype: adjusted OR=5.17; p-value=0.007; TT genotype: adjusted OR=6.28; p-value=0.027) remained associated with low HDL-c phenotype, together with hypertension and elevated body mass index, after multiple regression analysis. Conclusion. The variant rs1260326 near GCKR is associated with low HDL-c phenotype among Filipinos. Its role in the expression of low HDL-c phenotype should be further investigated prior to the development of possible clinical applications.