Bhatt D, Chauhan N, Sharma A, Dhawan D, Bhatt R V, Phatak S, Padh H
Department of Pharmacology, L. M. College of Pharmacy, Navrangpura, Ahmedabad-380 009, India.
Departments of Cellular and Molecular Biology, B. V. Patel PERD Centre, Thaltej, Ahmedabad-380 054, India.
Indian J Pharm Sci. 2014 Jan;76(1):72-7.
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 CYP2C92 and CYP2C93 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 CYP2C91, CYP2C92 and CYP2C93 alleles in the Gujarat state diabetic population were 0.84, 0.07 and 0.09, respectively. The distribution of CYP2C91/1, CYP2C91/2, CYP2C91/3, CYP2C92/2, CYP2C92/3 and CYP2C93/3 genotypes were 0.73, 0.08, 0.13, 0.0, 0.06 and 0.0, respectively. Patients with CYP2C91/2 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 CYP2C91/3 genotype showed greater mean glucose drop per milligram of drug values than patients with CYP2C91/1 wild-type genotype for both glipizide and glimepiride while patients with CYP2C92/3 genotype showed greater drop than patients with CYP2C91/1 genotype only in the glipizide-treatment group. The presence of CYP2C93 allele significantly affected plasma glucose drop per milligram of drug values in patients taking glipizide and glimepiride, while effects of CYP2C92 allele were insignificant. Further studies are needed to confirm the effects of CYP2C92 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.
本研究旨在探讨血浆葡萄糖浓度作为一种表型标志物的作用，并研究古吉拉特邦糖尿病患者中CYP2C9基因变异的频率分布。对109例接受磺脲类药物治疗的非亲缘关系糖尿病患者进行CYP2C92和CYP2C93等位基因基因分型。记录他们治疗前和治疗后的餐后血糖水平，并计算每毫克药物的平均血糖下降值，进一步将其用作表型相关性的指标。古吉拉特邦糖尿病患者中CYP2C91、CYP2C92和CYP2C93等位基因的频率分别为0.84、0.07和0.09。CYP2C91/1、CYP2C91/2、CYP2C91/3、CYP2C92/2、CYP2C92/3和CYP2C93/3基因型的分布分别为0.73、0.08、0.13、0.0、0.06和0.0。在格列吡嗪治疗组中，与野生型患者相比，CYP2C91/2基因型患者每毫克药物的平均血糖下降值没有显示出任何显著差异。在格列吡嗪和格列美脲治疗中，CYP2C91/3基因型患者每毫克药物的平均血糖下降值均高于CYP2C91/1野生型基因型患者；而仅在格列吡嗪治疗组中，CYP2C92/3基因型患者的血糖下降值高于CYP2C91/1基因型患者。CYP2C93等位基因的存在显著影响服用格列吡嗪和格列美脲患者每毫克药物的血浆葡萄糖下降值，而CYP2C92等位基因的影响不显著。需要进一步研究来证实CYP2C92等位基因对每毫克药物血浆葡萄糖下降值的影响。然而，血浆葡萄糖浓度是一个复杂的生理标志物，不能用于建立完美的基因型-表型相关性。因此，必须开展探索可靠表型标志物的研究。
