张亚楠,崔炜,韩梅,郑斌,刘凡,谢瑞芹,杨晓红,谷国强,郑红梅,温进坤.河北省汉族人群CYP450 2C9和VKORC1基因多态性与华法林剂量相关性研究[J].Chinese journal of Epidemiology,2010,31(2):218-222 |
河北省汉族人群CYP450 2C9和VKORC1基因多态性与华法林剂量相关性研究 |
Gene polymorphism of CYP450 2C9 and VKORCl in Chinese population and their relationships to the maintaining dosage of warfann |
Received:July 07, 2009 |
DOI: |
KeyWord: 华法林 基因多态性 多聚酶链反应 限制性片段长度多态性 |
English Key Word: Warfarin Gone polymorphism Polymerase chain reaction Restriction fragment length polymorphism |
FundProject: |
Author Name | Affiliation | E-mail | ZHANG Ya-nan | Department of Cardiology, The Second Hospital of Hebei Medical University and Institute of Cardiocerebrovascular Disease ofHebei Province, Shijiazhuang 050000, China | | CUl Wei | Department of Cardiology, The Second Hospital of Hebei Medical University and Institute of Cardiocerebrovascular Disease ofHebei Province, Shijiazhuang 050000, China | cuiwei@hb2h.com | HAN Mei | Department of Biochemistry and Molecular Biology, Institute of Basic Medicine, Hebei Medical University | | ZHENG Bin | Department of Biochemistry and Molecular Biology, Institute of Basic Medicine, Hebei Medical University | | LIUFan | Department of Cardiology, The Second Hospital of Hebei Medical University and Institute of Cardiocerebrovascular Disease ofHebei Province, Shijiazhuang 050000, China | | XlE Rui-qin | Department of Cardiology, The Second Hospital of Hebei Medical University and Institute of Cardiocerebrovascular Disease ofHebei Province, Shijiazhuang 050000, China | | YANG Xiao-hong | Department of Cardiology, The Second Hospital of Hebei Medical University and Institute of Cardiocerebrovascular Disease ofHebei Province, Shijiazhuang 050000, China | | GU Guo-qiang | Department of Cardiology, The Second Hospital of Hebei Medical University and Institute of Cardiocerebrovascular Disease ofHebei Province, Shijiazhuang 050000, China | | ZHENG Hong-mei | Department of Cardiology, The Second Hospital of Hebei Medical University and Institute of Cardiocerebrovascular Disease ofHebei Province, Shijiazhuang 050000, China | | WEN Jin-kun | Department of Biochemistry and Molecular Biology, Institute of Basic Medicine, Hebei Medical University | |
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Abstract: |
目的了解河北省汉族人群CYP450 2C9和VKORCl的基因多态性分布与其他不同民族之间的差异,探讨CYP450 2C9"3+1075C/A和VKORCl-1639A/G基闲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CYP450 2C9"3+1075C/A和VKORCl-1639A/G基因型及其分布频率,并与国外多个民族的CYP450 2C9"3+1075C/A和VKORCl-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,检测其基闪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CYP450 2C9"3+1075c/A基因型中,AA型为449名(92.2%),AC型36名(7.4%),CC型2名(O.4%);VKORCl-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:ln(D)=O.346+0.017(体重)一0.376(CYP450 2C9"3+1075C/A)+O.148(VKORCl-1639A/G)一0.002(年龄)(r=O.827,P=0.02)。结论汉族人群CYP450 2C9和VKORCl存在明显的基因多态性。CYP450 2C9"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。 |
English Abstract: |
Objective To investigate the distribution ofgene polymorphism ofCYP450 2C9 and VKORCl-1639A/G in the Chinese 130pulmion as well as the difference ofgenetic polymorphism between Chinese Hall population and other ethnic populations.Contribution ofCYP2C9 and VKORCl genotype to the maintenance doses 011 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 anticoagulafion with warfarin under a target international normalized ratio(INR)of 2.O to 3.0 Were enrolled for studying the relationship between the CYP2C9 and VKORCl gene polymorphism and the warfarin maintaining dosage.Results CYP450 2C9"3+1075C,A allele frequencies were:AA in 449 cases(92.2%)。AC in 36 cases(7.4%)and CC in 2 cases(0.4%),respectively.VKORCl一1639A/G allele frequencies were AA in 415 cases(85.2%).GA in 72 cases(14.8%)。but GG in no case(0.0%),respectively.、Vhen linear stegwise regression analysis Was used to identify factors contributing to warfarin stable dose,the final equation Was:In(D)=0.346+0.017(weight)一0.376(CYP450 2C9+3+1075C/A)+0.148(VKORCI一1639A/G)~0.002(age)(r=0.827,P=O.02).Conclusion There existed significant gene polymorphism CYP450 2C9*3+1075C/A and VKORCl一1639A/G in the Chinese Han population.Both Gene polymorphisms of CyP450 2C9"3+1075C/A and VKORCl一1639~fG were significantly affecting the maintaining dose ofwarfarin in the Chinese populatiOIL |
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