A genetic polymorphism in GCKR may be associated with low high-density lipoprotein cholesterol phenotype among Filipinos: A case-control study

@#<p style="text-align: justify;"><strong>Background.</strong> 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.</p><p style="text-align: justify;"><strong>Objective.</strong> To determine the association of selected genetic variants and clinical factors with low HDL-c phenotype in Filipinos.</p><p style="text-align: justify;"><strong>Methods.</strong> 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.</p><p style="text-align: justify;"><strong>Results.</strong> 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.</p><p style="text-align: justify;"><strong>Conclusion.</strong> 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.</p>

Variants near CETP, MTTP and BUD13-ZPR1-APOA5 may be nominally associated with poor statin response among Filipinos

@#<p style="text-align: justify;"><strong>Objective.</strong> Several studies showed that genetic factors affect responsiveness to statins among different populations. This study investigated the associations of candidate genetic variants with poor response to statins among Filipinos.</p><p style="text-align: justify;"><strong>Methods.</strong> In this unmatched case-control study, dyslipidemic participants were grouped into statin responders and poor responders based on the degree of reduction in LDL-c from baseline. DNA from blood samples were genotyped and analyzed. The association of candidate variants with statin response was determined using chi-square and logistic regression analysis.</p><p style="text-align: justify;"><strong>Results.</strong> We included 162 adults on statins (30 poor responders as cases, 132 good responders as controls). The following variants are nominally associated with poor response to statin among Filipinos at a per-comparison error rate of 0.05: rs173539 near CETP (OR=3.05, p=0.015), rs1800591 in MTTP (OR=3.07, p=0.021), and rs1558861 near the BUD13-ZPR1-APOA5 region (OR=5.08, p=0.004).</p><p style="text-align: justify;"><strong>Conclusion.</strong> Genetic variants near CETP, MTTP and the BUD13-ZPR1-APOA5 region are associated with poor response to statins among Filipinos. Further study is recommended to test the external validity of the study in the general Filipino population.</p>

Apolipoprotein levels in patients with Acute Coronary Syndrome (LIPAS): A pilot study

Introduction@#Lowering levels of low-density lipoprotein cholesterol (LDL-C) are proven to reduce cardiovascular risk. However, some individuals experience acute coronary events despite normal LDL-C levels. Recent studies have focused on modifiable lipoprotein targets, such as apolipoprotein B (apo-B) and apolipoprotein A-1 (apo A-1) and lipoprotein (a), as targets for therapy. Apo-B is the primary apolipoprotein of LDL-C representing total number of atherogenic particles. Apolipoprotein A-1 is the major component of HDL complex. This study will determine the prevalence of elevated apo-B and low apo A-1 among adult Filipinos with acute coronary syndrome (ACS).@*Methods@#This is a cross-sectional study involving 95 patients with ACS admitted in a tertiary hospital from November 2015 to May 2016. Levels of apo-B, apoA-1, lipoprotein (a), total cholesterol, triglyceride, LDL-C, and high-density lipoprotein cholesterol (HDL-C) were measured within 24 hours upon admission.@*Results@#Forty-eight (48%) percent of patients was diagnosed with Non ST-Elevation-ACS, 39% with ST-Elevation myocardial infarction (STEMI) and 13% with unstable angina.Thirtytwo (32%) percent were on low- to high-intensity statin treatment. The mean LDL-C, non-HDL-C, and HDL-C levels were 109 mg/dL, 135 mg/dL, and 36.89 mg/dL, respectively. The prevalence of elevated apo-B (mean=103.79 mg/ dL; target:<80 mg/dL) was 82%, while that of low apo A-1 (mean=119 mg/dL; target: >120 mg/dL for males, >140 mg/dL for females) was 63%. Lipoprotein (a) levels are high (mean = 48.51 nmol/L; normal:<35 nmol/L) in 42% of patients. Among those on statin therapy, the mean LDL-C was 85 mg/dl, but the mean apo B and lipoprotein (a) levels were elevated at 87.57 mg/dL and 41 nmol/L, respectively.@*Conclusion@#Elevated levels of apo B and lipoprotein (a) and low level of apo A-1 are highly prevalent in patients with ACS. Apo-B and lipoprotein (a) levels are likewise elevated among patients with normal LDL levels.