Rathore Saurabh Singh, Agarwal Surendra Kumar, Pande Shantanu, Singh Sushil Kumar, Mittal Tulika, Mittal Balraj
Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India.
Indian J Med Res. 2014 Apr;139(4):572-8.
BACKGROUND & OBJECTIVES: CYP4F2 and γ-glutamyl carboxylase (GGCX) have small but significant roles in the maintenance dose of coumarinic oral anticoagulants (COAs). CYP4F2 1347 G > A and GGCX 12970 C > G polymorphisms have been used in the pharmacogenetic dosing algorithms of warfarin for Caucasians and Chinese populations. India has a large population with multiple ethnic groups but there are no reports about the frequencies of these polymorphisms in north Indians. In the present study, we aimed to find out the allelic frequencies of CYP4F2 1347 G > A and GGCX 12970 C > G polymorphisms in a north Indian population and relate these to daily maintenance drug dose requirements of COA.
CYP4F2 1347 G > A and GGCX 12970 C > G polymorphisms were genotyped by polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) protocols and Taqman SNP discrimination assays in healthy volunteers (n=102) and patients (n=225) receiving acenocoumarol, an oral anticoagulant, after cardiac valve replacement surgery.
In healthy volunteers, the allele frequencies for CYP4F2 1347 G > A and GGCX 12970 C > G were 43.14 and 1.43 per cent, respectively. No significant differences in mean weight normalized doses of acenocoumarol were found for these CYP4F2 and GGCX genotypes. Binary logistic regression analysis revealed no significant association of any of the genotypes or alleles with the dosing phenotypes for both the SNPs.
INTERPRETATION & CONCLUSIONS: We report distinct frequencies of CYP4F2 1347 G > A and GGCX 12970 C > G polymorphisms in north Indians but these polymorphisms did not have significant bearing on maintenance dose of acenocoumarol oral anticoagulant in cardiac valve replacement patients.
细胞色素P450 4F2（CYP4F2）和γ-谷氨酰羧化酶（GGCX）在香豆素类口服抗凝剂（COA）维持剂量方面发挥着虽小但显著的作用。CYP4F2基因1347位G>A和GGCX基因12970位C>G多态性已应用于白种人和中国人群华法林的药物遗传学给药算法中。印度人口众多且种族多样，但尚无关于北印度人这些多态性频率的报道。在本研究中，我们旨在确定北印度人群中CYP4F2基因1347位G>A和GGCX基因12970位C>G多态性的等位基因频率，并将其与COA的每日维持药物剂量需求相关联。
采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法和Taqman单核苷酸多态性鉴别分析，对心脏瓣膜置换术后接受口服抗凝剂醋硝香豆素的健康志愿者（n = 102）和患者（n = 225）进行CYP4F2基因1347位G>A和GGCX基因12970位C>G多态性基因分型。
在健康志愿者中，CYP4F2基因1347位G>A和GGCX基因12970位C>G的等位基因频率分别为43.14%和1.43%。对于这些CYP4F2和GGCX基因型，醋硝香豆素平均体重标准化剂量未发现显著差异。二元逻辑回归分析显示两个单核苷酸多态性的任何基因型或等位基因与给药表型均无显著关联。
我们报道了北印度人群中CYP4F2基因1347位G>A和GGCX基因12970位C>G多态性的不同频率，但这些多态性对心脏瓣膜置换患者醋硝香豆素口服抗凝剂的维持剂量没有显著影响。
