EVALUATION OF CANDIDATE GENETIC VARIATIONS AS PHARMACOGENETIC MARKERS FOR GLICLAZIDE AMONG FILIPINOS
Keywords:pharmacogenetics, diabetes mellitus, type 2, gliclazide
To determine the genetic polymorphisms associated with drug response to gliclazide in type 2 diabetes mellitus (T2DM).
This was an unmatched case-control study comparing response to gliclazide. Participants were enrolled from three (3) institutions (Philippine General Hospital, Corazon Locsin Montelibano Memorial Regional Hospital and Southern Philippines Medical Center) and its surrounding communities. One hundred thirty-nine adult Filipinos with newly diagnosed T2DM were enrolled to determine the association of genetic variants in response to gliclazide. Glycosylated hemoglobin (HbA1c) collected 3 months apart was used to determine response. DNA from blood samples were genotyped using Infinium iSelect beadchips. Candidate variants were then correlated with response to gliclazide using t-test, chi-square and univariate logistic regression analysis.
PRELIMINARY RESULTS AND DISCUSSION
Four (4) candidate genetic variants associated with response to gliclazide were revealed. The two most significant single nucleotide polymorphisms (SNP) are variants of the gene 5-hydroxytryptamine receptor 2C (HTR2C) (CC > > GC > GG: OR 28.20, 95% CI 2.59, 1,464.13; p-value 0.0015 and AA vs. GG + AG: OR 0.04, 95% CI 0.00069, 0.389; p-value 0.0015 respectively). The third SNP is a variant of the gene high mobility group 20A (HMG20A) (AA > AG > GG: OR 3.70, 95% CI 1.50, 10.03; p-value 0.0018).
The study revealed SNPs that were not previously associated with response to gliclazide. These may be further investigated and validated to identify markers for response to this medication. This will be the basis for matching of patients with the appropriate medications and hence provide improved outcomes
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