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

  • Rody G. Sy Department of Medicine, University of the Philippines, Philippine General Hospital
  • Jose B. Nevado, Jr. Institute of Human Genetics, National Institutes of Health
  • Eddieson M. Gonzales Department of Medicine, University of the Philippines, Philippine General Hospital
  • Adrian John P. Bejarin Institute of Human Genetics, National Institutes of Health
  • Aimee Yvonne Criselle L. Aman Institute of Human Genetics, National Institutes of Health
  • Elmer Jasper B. Llanes Department of Medicine, University of the Philippines, Philippine General Hospital
  • Jose Donato A. Magno Department of Medicine, University of the Philippines, Philippine General Hospital
  • Deborah Ignacia D. Ona Department of Medicine, University of the Philippines, Philippine General Hospital
  • Felix Eduardo R. Punzalan Department of Medicine, University of the Philippines, Philippine General Hospital
  • Paul Ferdinand M. Reganit Department of Medicine, University of the Philippines, Philippine General Hospital
  • Lourdes Ella G. Santos Department of Medicine, University of the Philippines, Philippine General Hospital
  • Richard Henry P. Tiongco II Department of Medicine, University of the Philippines, Philippine General Hospital
  • Jaime Alfonso M. Aherrera Department of Medicine, University of the Philippines, Philippine General Hospital
  • Lauro L. Abrahan IV Department of Medicine, University of the Philippines, Philippine General Hospital
  • Charlene F. Agustin Department of Medicine, University of the Philippines, Philippine General Hospital
  • Eva Maria C. Cutiongco - de la Paz National Institutes of Health; Philippine Genome Center
Keywords: cardiovascular disease, dyslipidemia, GCKR, genetics, single nucleotide polymorphism, rs1260326

Abstract

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.

Author Biographies

Rody G. Sy, Department of Medicine, University of the Philippines, Philippine General Hospital

Professor Emeritus

University of the Philippines College of Medicine

Jose B. Nevado, Jr., Institute of Human Genetics, National Institutes of Health

Research Professor

National Institutes of Health

Eddieson M. Gonzales, Department of Medicine, University of the Philippines, Philippine General Hospital

Clinical Fellow

Division of Adult Cardiology

Department of Medicine

Adrian John P. Bejarin, Institute of Human Genetics, National Institutes of Health

Senior Research Associate

Institute of Human Genetics

National Institutes of Health

Aimee Yvonne Criselle L. Aman, Institute of Human Genetics, National Institutes of Health

Senior Research Specialist

Institute of Human Genetics

National Institutes of Health

Elmer Jasper B. Llanes, Department of Medicine, University of the Philippines, Philippine General Hospital

Clinical Associate Professor

Division of Adult Cardiology

Department of Medicine, Philippine General Hospital

 

Jose Donato A. Magno, Department of Medicine, University of the Philippines, Philippine General Hospital

Clinical Associate Professor

Division of Adult Cardiology

Department of Medicine, Philippine General Hospital

Deborah Ignacia D. Ona, Department of Medicine, University of the Philippines, Philippine General Hospital

Clinical Associate Professor

Department of Medicine

Philippine General Hospital

Felix Eduardo R. Punzalan, Department of Medicine, University of the Philippines, Philippine General Hospital

Medical Specialist

Department of Medicine

Philippine General Hospital

Paul Ferdinand M. Reganit, Department of Medicine, University of the Philippines, Philippine General Hospital

Clinical Associate Professor

Division of Adult Cardiology

Department of Medicine, Philippine General Hospital

Lourdes Ella G. Santos, Department of Medicine, University of the Philippines, Philippine General Hospital

Clinical Associate Professor

Division of Adult Cardiology

Department of Medicine, Philippine General Hospital

Richard Henry P. Tiongco II, Department of Medicine, University of the Philippines, Philippine General Hospital

Associate Professor 6

Department of Medicine

Philippine General Hospital

Jaime Alfonso M. Aherrera, Department of Medicine, University of the Philippines, Philippine General Hospital

Clinical Fellow

Division of Adult Cardiology

Department of Medicine, Philippine General Hospital

Lauro L. Abrahan IV, Department of Medicine, University of the Philippines, Philippine General Hospital

Clinical Fellow

Division of Adult Cardiology

Department of Medicine, Philippine General Hospital

Charlene F. Agustin, Department of Medicine, University of the Philippines, Philippine General Hospital

Clinical Fellow

Division of Adult Cardiology

Department of Medicine, Philippine General Hospital

Eva Maria C. Cutiongco - de la Paz, National Institutes of Health; Philippine Genome Center

Executive Director

National Institutes of Health

 

Program Director

Philippine Genome Center

Published
2021-06-14
Section
Articles

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