EVALUATION OF CANDIDATE GENETIC VARIATIONS AS PHARMACOGENETIC MARKERS FOR METFORMIN AMONG FILIPINOS

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

Authors

Elizabeth Paz-Pacheco Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of the Philippines – Philippine General Hospital Manila
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
Gabriel Jasul Jr. Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of the Philippines – Philippine General Hospital Manila
May Uyking-Naranjo Southern Philippines Medical Center
Ma. Luz Vicenta Guanzon Corazon Locsin Montelibano Memorial Regional Hospital, Bacolod, Negros Occidental, Philippines
Karell Jo Angelique Calpito 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
Vincent Sean Ribaya 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:

pharmacogenetics, diabetes mellitus, type 2, metformin

Abstract

INTRODUCTION
This study aims to determine the genetic polymorphisms associated with drug response to metformin in type 2 diabetes mellitus (T2DM).

METHODOLOGY
Unmatched cases and controls were used to test the association of genetic polymorphisms in candidate genes to test drug response to metformin. Two hundred fifteen patients with type 2 diabetes who were diagnosed within the past 3 years, without recent T2DM treatment were enrolled simultaneously from three (3) hospitals from Luzon, Visayas and Mindanao and various communities around its area. The participants were started on metformin as monotherapy for 3 months. Glycosylated hemoglobin (HbA1c) was measured at baseline and after 3 months of treatment. Genotyping was done using customized Illumina Infinium microarray chips. Candidate variants were then correlated with response using logistic regression analysis.

PRELIMINARY RESULTS and DISCUSSION
There are three (3) candidate genetic variants significantly associated to metformin response in this study. The two most significant single nucleotide polymorphisms (SNPs) are variants of the gene FK506-binding protein 5 gene (FKBP5) (AA > AC > CC: OR 3.44, 95% CI 1.67, 7.76; p-value 0.0004 and CC > CT > TT: OR 3.45, 95% CI 1.64, 8.06; p-value 0.0006, respectively).

CONCLUSION
The study revealed SNPs that were not previously associated with metformin response. Genetic variation exists among Filipinos and these influence treatment responses to oral hypoglycemic agents. This study on the genetics of Filipinos with diabetes will potentially benefit the population with use of appropriate medications.