海南省黎族与汉族持续性心房颤动患者CYP2C9^*3基因多态性差异

Different genetic polymorphisms of CYP2C9*3 in Li and Han population patients with persistent atrial fibrillation in Hainan Province

目的:分析罹患持续性心房颤动的海南省黎族与汉族患者细胞色素P450酶2C9^*3(CYP2C9^*3)基因多态性分布,评估CYP2C9^*3基因多态性对患者稳定服用华法林剂量的影响。方法:选取2017年1月至2018年12月于海南医学院第二附属医院就诊的罹患持续性心房颤动的海南省黎族患者100例为研究组,同期海南医学院第二附属医院持续性心房颤动的汉族患者100例为对照组。记录两组研究对象的血清华法林浓度、国际标准化比率(international normalized ratio,INR)达标时间、华法林平均日剂量及总剂量;提取两组基因组DNA,采用扩增阻滞突变体系-聚合酶链式反应技术(amplification refractory mutation system,ARMS-PCR)对CYP2C9^*3基因位点进行基因分型。结果:研究组患者A/A与A/C基因型及等位基因A频率显著低于对照组(P<0.05),C/C基因型及C频率显著高于对照组(P<0.05)。两组不同基因型患者华法林稳定剂量及血清华法林浓度存在差异,均为A/A型最大(P<0.05),而A/C型与C/C型无差异(P>0.05);研究组A/A基因型患者华法林稳定剂量及血清华法林浓度低于对照组(P<0.05),但两组A/C与C/C基因型患者华法林稳定剂量及血清华法林浓度均无差异(P>0.05)。A/A基因型黎族持续性心房颤动患者的INR达标时间、华法林平均日剂量及总剂量最高,C/C基因型最低,A/C基因型次之(P<0.05)。结论:CYP2C9基因多态性与持续性心房颤动的海南省黎族患者稳定服用华法林剂量密切相关,C/C型CYP2C9基因持续性心房颤动的海南省黎族患者INR达标时间、华法林平均日剂量及总剂量更低。

Objective:To investigate the association of genetic polymorphisms in CYP2C9*3 with warfarin dosage in Li population patients with persistent atrial fibrillation(PAF)in Hainan Province.Methods:A total of 100 Li population patients diagnosed as PAF in our hospital were collected to research group.And 100 Han population patients diagnosed as PAF in the same hospital were collected to control group from January 2017 to December 2018.The indexes of serum warfarin levels,international normalized ratio(INR)standard time,warfarin average daily dosage and warfarin total dosage of two groups were recorded.The DNA samples of two groups were extracted.Then the SNP sites of CYP2C9*3 gene were genotyped by amplification refractory mutation system(ARMS-PCR)method.Results:Compared to control group,the genotype frequencies of A/A and A/C and the allele frequency of A in research group were lower(P<0.05),and the genotype frequencies of C/C and the allele frequency of C in research group were higher(P<0.05).The warfarin stable dosage and serum warfarin levels in two groups were different among three genotypes(P<0.05).The A/A genotype of warfarin stable dosage levels and serum warfarin levels was highest,and the A/C and C/C genotypes were no different(P>0.05).The A/A genotype of warfarin stable dosage levels and serum warfarin levels in research group was lower than in control group(P<0.05),but the A/C and C/C genotype of warfarin stable dosage levels and serum warfarin levels were no different between two groups(P>0.05).The INR standard time,warfarin average daily dosage and warfarin total dosage of Li population patients with PAF were different,and the sequence were A/A>C/C>A/C(P<0.05).Conclusion:The polymorphisms on CYP2C9*3 gene is related to warfarin stable dosage levels of Li population patients with PAF.And the INR standard time,warfarin average daily dosage and warfarin total dosage with C/C genotype of CYP2C9*3 gene are lower than those with A/A and A/C.