CORRELATION OF CANDIDATE GENETIC VARIATIONS FOR SUSCEPTIBILITY AND RISK ASSESSMENT OF TYPE 2 DIABETES MELLITUS AMONG FILIPINOS

Eva Maria  Cutiongco-de la Paz; Jose Nevado Jr.; Elizabeth Paz-Pacheco; Gabriel Jasul Jr.; Vincent Sean Ribaya; Elizabeth Laurize Alejandro; Karell Jo Angelique Calpito; Julius Patrick Ferrer

Authors

Eva Maria Cutiongco-de la Paz Institute of Human Genetics, National Institutes of Health, University of the Philippines, Manila
Jose Nevado Jr. Institute of Human Genetics, National Institutes of Health, University of the Philippines, Manila
Elizabeth Paz-Pacheco Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of the Philippines – Philippine General Hospital, Manila
Gabriel Jasul Jr. Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of the Philippines – Philippine General Hospital, Manila
Vincent Sean Ribaya Institute of Human Genetics, National Institutes of Health, University of the Philippines, Manila
Elizabeth Laurize Alejandro Institute of Human Genetics, National Institutes of Health, University of the Philippines, Manila
Karell Jo Angelique Calpito Institute of Human Genetics, National Institutes of Health, University of the Philippines, Manila
Julius Patrick Ferrer Institute of Human Genetics, National Institutes of Health, University of the Philippines, Manila

Keywords:

diabetes mellitus, type 2, genetic susceptibility, genotyping

Abstract

OBJECTIVES
The study aims to determine genetic variants associated with type 2 diabetes mellitus (T2DM) that can help in the development of personalized care for Filipinos.

METHODOLOGY
A total of 201 unrelated adult Filipinos were enrolled in this matched case-control study (67 cases with T2DM to 134 controls). DNA from blood was genotyped via customized Illumina (GoldenGate Genotyping and Infinium iSelect) microarray beadchips, investigating 357 candidate genetic variants associated with T2DM. Correlation with T2DM was done via permuted Pearson chi-square tests of allelic/ genotypic association, Bonferroni correction for multiplicity, and Efron conditional logistic regression analysis.

RESULTS AND DISCUSSION
Three (3) candidate variants exhibited significant association with T2DM among Filipinos. A CDKAL1 (cyclin-dependent kinase 5 regulatory subunit-associated protein 1 like 1 gene) variant showed the greatest risk in association (AA > AC > CC: OR 10.08, 95% CI 5.21, 19.53; p 0.0145). Other variants showed significance, namely a SERPINF1 (serpin family member 1 gene) variant (CC > CT > TT: OR 5.43, 95% CI 2.84, 10.38; p 0.0164) and a GPR45 (G protein-coupled receptor 45 gene) variant (CC > CT > TT: OR 2.56, 95% CI 1.43, 4.59; p 0.0206).

CONCLUSION
Preliminary results present variations in CDKAL1, SERPINF1, and GPR45 significantly associated with T2DM which may be further investigated through clinical validation to develop diagnostic/prognostic markers for T2DM in Filipinos. Though Philippine genetic studies for T2DM are limited, the emergence of genetic research and genotyping technology presents the opportunity to better optimize T2DM management and treatment in the Filipino individual.