摘要
目的研究上海地区服用华法林人群相关基因型及性别、体重等非遗传因素与华法林用药剂量问的关系。方法选取服用华法林至稳定剂量且国际标准化比值（mR）为1．5-3．0的患者214例，收集其临床资料（包括性别、年龄和华法林剂量）；采用聚合酶链反应一高分辨率熔解（PCR—HRM）技术建立华法林关联基因CYP2C9＊2rs1799853、CYP2C9＊3rs1057910、CYP4F2rs2108622和VKORC1 rs9934438四个单核苷酸多态性（SNP）位点的临床快速基因分型技术，测定患者SNP位点的多态性，分析基因型、性别、体重、年龄等因素与用药剂量的关系。结果全部214例患者中，CYP2C9＊2rsl799853基因CC型（野生型）占99．53％（213例），CT型（杂合突变型）仅0．47％（1例）；CYP2C9＊3rsl057910基因AA型（野生型）占92．52％（198例），CA型（杂合突变型）占7．48％（16例）；CYP4F2rs2108622基因CC型（野生型）占57．94％（124例），CT型（杂合突变型）＋TT型（纯合突变型）占42．06％（90例）；VKORClrs9934438基因TT型（野生型）占82．71％（177例），CT型（杂合突变型）占17．29％（37例）。不同基因型患者华法林维持剂量比较：CYP2C9＊3基因AA型与CA型差异无统计学意义[（2．816±1．055）mg／d对（2．352＋0．805）mg／a，P=0．0872]；CYP4F2基因CC型与CT＋TT型差异无统计学意义[（2．736±1．062）mg／a对（2．813±1．034）mg／d，P=0．5954]；VKORC1基因TT型与CT型差异有统计学意义[（2．597±0．866）mg／d对（3．660±1．350）mg／d，尸=0．0001]。患者平均年龄与华法林维持剂量呈负相关（r=-0．9669）；患者平均体重与华法林维持剂量呈正相关（r=0．9022）。结论上海地区患者可通过检测VKORCl基因型进行华法林剂量调整。
Objective To investigate the distribution of Warfarin related genes and the relationship between genotype,gender,weight,age and the administrative dose of Warfarin in Shanghai area.Methods The clinical data (including sex,age and administrative dose of Warfarin) of 214 patients with stable warfarin dose and the international normalized ratio (INR) between 1.5-3.0 were collected.Polymerase chain reaction-high resolution melting (PCR-HRM) technique was used to detect the single nucleotide polymorphisms (SNPs) of CYP2C9*2 rs1799853,CYP2C9*3 rs1057910,CYP4F2 rs2108622 and VKORC1 rs9934438.The associations of genotype data with clinical material,including gender,age,weight and warfarin dosage were analyzed.Results Among 214 patients,99.53％ (213 cases) patients with CC (wild type) of CYP2C9*2 rs1799853 and only 1 case with CT (heterozygous mutation); 92.52％(198 cases) with AA (wild type),7.48％ (16 cases) with CA (heterozygous mutation) of CYP2C9*3 rs1057910; about 57.94％ (124 cases) with CC (wild type) of CYP4F2 rs2108622,the CT and TT (heterozygous and homozygotic mutation) accounted for 42.06％ (90 cases).In SNP VKORC1 rs9934438,82.71％ (177cases) were TT (wild type),17.29％ (37 cases) CT (heterozygous mutation).There are no significant difference (P=0.0872) in patients with maintenance dose in CYP2C9*3 between AA and CA gene mutations [(2.816± 1.055) mg/d vs (2.352±0.805) mg/d],and no significant difference (P=0.5954) of that in CYP4F2 between CC and CT+TT gene mutations [(2.736±1.062) mg/d vs (2.813±1.034) mg/d]; but the significant differences (P=0.0001) does exist in patients with maintenance dose in VKORC1 between TT and CT variants [(2.597±0.866) mg/d vs (3.660± 1.350) mg/d].The warfarin maintain dosage was negatively correlated with the average age (r=-0.9669) and positively correlated with the body weight (r=0.9022).Conclusion It is of great significance to detect the VKORC1 variants for warfarin dosage adjustment in Shanghai population.However,the detection of CYP2C9*2 and CYP4F2 polymorphisms had no significant associations for warfarin dosage adjustment.
出处
《中华血液学杂志》
CAS
CSCD
北大核心
2014年第1期13-17,共5页
Chinese Journal of Hematology
基金
上海市长宁区科委重点项目（CNKW2013202）
