河北省汉族人群CYP4502C9和VKORC1基因多态性与华法林剂量相关性研究  

Gene polymorphism of CYP450 2C9 and VKORC1 in Chinese population and their relationships to the maintaining dosage of warfarin

作　　者：张亚楠[1] 崔炜[1] 韩梅[2] 郑斌[2] 刘凡[1] 谢瑞芹[1] 杨晓红[1] 谷国强[1] 郑红梅[1] 温进坤[2] 

机构地区：[1]河北医科大学第二医院河北省心脑血管病研究所心内科,石家庄050000 [2]河北医科大学基础医学研究所生物化学与分子生物学研究室

出　　处：《中华流行病学杂志》2010年第2期218-222,共5页Chinese Journal of Epidemiology

摘　　要：目的了解河北省汉族人群CYP4502C9和VKORC1的基因多态性分布与其他不同民族之间的差异，探讨CYP4502C9＊3＋1075C／A和VKORC1—1639A／G基因多态性与华法林剂量的关系。方法随机选取门诊体检的健康人487名，检测CYP4502C9＊3＋1075C／A和VKORC1—1639A／G基因型及其分布频率，并与国外多个民族的CYP4502C9＊3＋1075C／A和VKORC1—1639A／G的基因多态性进行比较。选取服用华法林稳定剂量的患者101例，检测其基因型并结合其个体差异和华法林的稳定剂量进行分析。结果487名正常人CYP4502C9＊3＋1075C／A基因型中，AA型为449名（92．2％），AC型36名（7．4％），CC型2名（0．4％）；VKORC1—1639A／G基因型中AA型为415名（85-2％），GA型72名（14．8％），未发现GG型（0．0％）。采用多元逐步回归得出有关华法林稳定剂量的方程：In（D）=0．346＋O．017（体重）-0．376（CYP4502C9＊3＋1075C／A）＋0．148（VKORCl—1639A／G）-O．002（年龄）（r=0．827，P=0．02）。结论汉族人群CYP4502C9和VKORCl存在明显的基因多态性。CYP4502C9＊3＋1075C／A和VKORCl—1639A／G的基因型和患者个体之间的体重、年龄差异是影响华法林稳定剂量的因素。Objective To investigate the distribution ofgene polymorphism of CYP450 2C9 and VKORCl-1639A/G in the Chinese population as well as the difference of genetic polymorphism between Chinese Han population and other ethnic populations. Contribution of CYP2C9 and VKORC 1 genotype to the maintenance doses on warfarin was also studied. Methods The genotype and allele frequencies were calculated and compared with those in other populations. One hundred and one patients with stable anficoagulation with warfarin under a target international normalized ratio （INR） of 2.0 to 3.0 were enrolled for studying the relationship between the CYP2C9 and VKORC1 gene polymorphism and the warfarin maintaining dosage. Results CYP450 2C9＊3 ＋ 1075C/A allele fi＇equencies were： AA in 449 cases （92.2%）, AC in 36 cases （7.4%） and CC in 2 cases （0.4%）, respectively. VKORC1 -1639A/G allele frequencies were AA in 415 cases （85.2%）, GA in 72 cases （ 14.8% ）, but GG in no case （0.0%）, respectively. When linear stepwise regression analysis was used to identify factors contributing to warfarin stable dose, the final equation was： ln（D） = 0.346 ＋ 0.017 （weight） - 0.376 （CYP450 2C9＊3 ＋1075C/ A） ＋ 0.148 （VKORCl-1639A/G） - 0.002 （age） （r=0.827, P=0.02）. Conclusion There existed significant gene polynaorphism CYP450 2C9＊3＋ 1075C/A and VKORCl-1639A/G in the Chinese Han population. Both Gene polymorphisms of CYP450 2C9＊3 ＋ 1075C/A and VKORCI-1639A/G were significantly affecting the maintaining dose of warfarin in the Chinese population.

关 键 词：华法林 基因多态性 多聚酶链反应 限制性片段长度多态性 

分 类 号：R394[医药卫生—医学遗传学]