EVALUATION OF CANDIDATE GENETIC VARIATIONS AS PHARMACOGENETIC MARKERS FOR METFORMIN AMONG FILIPINOS
Keywords:pharmacogenetics, diabetes mellitus, type 2, metformin
This study aims to determine the genetic polymorphisms associated with drug response to metformin in type 2 diabetes mellitus (T2DM).
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).
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.
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