Investigating the Role of Plasma Glucose Concentration as a Phenotypic Marker for CYP2C9 Genetic Variants, in the Diabetic Population of Gujarat

Abstract

The present study was aimed to investigate the role of plasma glucose concentration as a phenotypic marker and to study the frequency distribution of CYP2C9 genetic variants in Gujarat state diabetic population. One hundred and nine unrelated diabetes mellitus patients treated with sulfonylureas were genotyped for CYP2C9*2 and CYP2C9*3 alleles. Their pre- and posttreatment postprandial blood glucose levels were recorded and mean glucose drop per milligram of drug values were calculated and further used as an index for phenotypic correlation. The frequencies of CYP2C9*1, CYP2C9*2 and CYP2C9*3 alleles in the Gujarat state diabetic population were 0.84, 0.07 and 0.09, respectively. The distribution of CYP2C9*1/*1, CYP2C9*1/*2, CYP2C9*1/*3, CYP2C9*2/*2, CYP2C9*2/*3 and CYP2C9*3/*3 genotypes were 0.73, 0.08, 0.13, 0.0, 0.06 and 0.0, respectively. Patients with CYP2C9*1/*2 genotype did not show any significant difference in the mean glucose drop per milligram of drug values when compared with wild-type patients in glipizide-treatment group. Patients with CYP2C9*1/*3 genotype showed greater mean glucose drop per milligram of drug values than patients with CYP2C9*1/*1 wild-type genotype for both glipizide and glimepiride while patients with CYP2C9*2/*3 genotype showed greater drop than patients with CYP2C9*1/*1 genotype only in the glipizide-treatment group. The presence of CYP2C9*3 allele significantly affected plasma glucose drop per milligram of drug values in patients taking glipizide and glimepiride, while effects of CYP2C9*2 allele were insignificant. Further studies are needed to confirm the effects of CYP2C9*2 allele on plasma glucose drop per milligram of drug values. However, plasma glucose concentration is a complex physiological marker that cannot be used to establish perfect genotype-phenotype correlation. Hence studies exploring robust phenotypic markers must be initiated.

Keywords: CYP2C9; diabetes; phenotypic marker; plasma glucose; sulfonylurea.

Fig. 1

Fig. 2

Mean DPM values for different genotypic groups in the glipizide treatment group. Sample size is n=46, 7, 7 and 4 for CYP2C9*1/*1, CYP2C9*1/*2, CYP2C9*1/*3 and CYP2C9*2/*3 genotypic groups, respectively; a represents significant difference (P<0.05) from the CYP2C9*1/*1 group while b represents significant difference (P <0.05) from the CYP2C9*1/*2 group; each value is the mean±SEM of glucose drop per milligram of the drug (DPM).

Fig. 3

Mean DPM values for different genotypic groups in the glimepiride treatment group. Sample size is n=26, 1, 3 and 0 for CYP2C9*1/*1, CYP2C9*1/*2, CYP2C9*1/*3 and CYP2C9*2/*3 genotypic groups, respectively; a represents significant difference (P<0.05) from the CYP2C9*1/*1 group; each value is the mean±SEM of glucose drop per milligram of the drug (DPM).