中华血液学杂志
中華血液學雜誌
중화혈액학잡지
Chinese Journal of Hematology
2014年
1期
13-17
,共5页
华法林%基因型%药物剂量计算
華法林%基因型%藥物劑量計算
화법림%기인형%약물제량계산
Warfarin%Genotype%Drug dosage calculations
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间的关系.方法 选取服用华法林至稳定剂量且国际标准化比值(INR)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-高分辨率熔解(PCR-HRM)技术建立华法林关联基因CYP2C9*2 rs 1799853、CYP2C9*3 rs 1057910、CYP4F2 rs 2108622和VKORC1rs 9934438四个单核苷酸多态性(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*2rs1799853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*3rs1057910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);VKORC1 rs9934438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/d,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/d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,P=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VKORC1基因型进行华法林剂量调整.
目的 研究上海地區服用華法林人群相關基因型及性彆、體重等非遺傳因素與華法林用藥劑量間的關繫.方法 選取服用華法林至穩定劑量且國際標準化比值(INR)為1.5～3.0的患者214例,收集其臨床資料(包括性彆、年齡和華法林劑量);採用聚閤酶鏈反應-高分辨率鎔解(PCR-HRM)技術建立華法林關聯基因CYP2C9*2 rs 1799853、CYP2C9*3 rs 1057910、CYP4F2 rs 2108622和VKORC1rs 9934438四箇單覈苷痠多態性(SNP)位點的臨床快速基因分型技術,測定患者SNP位點的多態性,分析基因型、性彆、體重、年齡等因素與用藥劑量的關繫.結果 全部214例患者中,CYP2C9*2rs1799853基因CC型(野生型)佔99.53％(213例),CT型(雜閤突變型)僅0.47％(1例);CYP2C9*3rs1057910基因AA型(野生型)佔92.52％(198例),CA型(雜閤突變型)佔7.48％(16例);CYP4F2rs2108622基因CC型(野生型)佔57.94％(124例),CT型(雜閤突變型)+TT型(純閤突變型)佔42.06％(90例);VKORC1 rs9934438基因TT型(野生型)佔82.71％(177例),CT型(雜閤突變型)佔17.29％(37例).不同基因型患者華法林維持劑量比較:CYP2C9*3基因AA型與CA型差異無統計學意義[(2.816±1.055)mg/d對(2.352±0.805)mg/d,P=0.0872];CYP4F2基因CC型與CT+TT型差異無統計學意義[(2.736±1.062)mg/d對(2.813±1.034)mg/d,P=0.5954];VKORC1基因TT型與CT型差異有統計學意義[(2.597±0.866)mg/d對(3.660±1.350)mg/d,P=0.0001].患者平均年齡與華法林維持劑量呈負相關(r=-0.9669);患者平均體重與華法林維持劑量呈正相關(r=0.9022).結論 上海地區患者可通過檢測VKORC1基因型進行華法林劑量調整.
목적 연구상해지구복용화법림인군상관기인형급성별、체중등비유전인소여화법림용약제량간적관계.방법 선취복용화법림지은정제량차국제표준화비치(INR)위1.5～3.0적환자214례,수집기림상자료(포괄성별、년령화화법림제량);채용취합매련반응-고분변솔용해(PCR-HRM)기술건립화법림관련기인CYP2C9*2 rs 1799853、CYP2C9*3 rs 1057910、CYP4F2 rs 2108622화VKORC1rs 9934438사개단핵감산다태성(SNP)위점적림상쾌속기인분형기술,측정환자SNP위점적다태성,분석기인형、성별、체중、년령등인소여용약제량적관계.결과 전부214례환자중,CYP2C9*2rs1799853기인CC형(야생형)점99.53％(213례),CT형(잡합돌변형)부0.47％(1례);CYP2C9*3rs1057910기인AA형(야생형)점92.52％(198례),CA형(잡합돌변형)점7.48％(16례);CYP4F2rs2108622기인CC형(야생형)점57.94％(124례),CT형(잡합돌변형)+TT형(순합돌변형)점42.06％(90례);VKORC1 rs9934438기인TT형(야생형)점82.71％(177례),CT형(잡합돌변형)점17.29％(37례).불동기인형환자화법림유지제량비교:CYP2C9*3기인AA형여CA형차이무통계학의의[(2.816±1.055)mg/d대(2.352±0.805)mg/d,P=0.0872];CYP4F2기인CC형여CT+TT형차이무통계학의의[(2.736±1.062)mg/d대(2.813±1.034)mg/d,P=0.5954];VKORC1기인TT형여CT형차이유통계학의의[(2.597±0.866)mg/d대(3.660±1.350)mg/d,P=0.0001].환자평균년령여화법림유지제량정부상관(r=-0.9669);환자평균체중여화법림유지제량정정상관(r=0.9022).결론 상해지구환자가통과검측VKORC1기인형진행화법림제량조정.
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.
