CAJ | 학술논문

华法林%细胞色素P450 2C9%维生素K氧化还原酶复合体系1%细胞色素P450氧化还原酶POR%单核苷酸多态性%人工心脏机械瓣膜置换术%剂量个体差异華法林%細胞色素P450 2C9%維生素K氧化還原酶複閤體繫1%細胞色素P450氧化還原酶POR%單覈苷痠多態性%人工心髒機械瓣膜置換術%劑量箇體差異
화법림%세포색소P450 2C9%유생소K양화환원매복합체계1%세포색소P450양화환원매POR%단핵감산다태성%인공심장궤계판막치환술%제량개체차이
warfarin%cytochrome P450 2 C9%vitamin K epoxide reductase complex 1%cytochrome P450 oxi-doreductase%single nucleotide polymorphism%artificial mechanical heart valve replacement%inter-individual variation

目的探讨POR基因多态性与华法林维持剂量的相关性。方法共纳入185例中国汉族人工心脏机械瓣膜置换术患者,采用 Sequenom MassARRAY? System 检测VKORC1及 POR 相关 SNPs,采用 PCR-RFLP 法检测CYP2C9*3基因型。采用 ANOVA 或 t检验考察目的 SNPs与患者华法林维持剂量的关系。结果在CYP2C9*1*1携带者中,POR rs17685 T等位基因携带者( TT型和CT型)华法林维持剂量明显高于 CC 型携带者(3．50±1．07) mg · d-1 vs (3．14±0．94) mg·d-1,P=0．03。在CYP2C9*1*1及VKORC1 rs9934438 GA/GG携带者中, POR rs17685 T等位基因携带者( TT型和CT型)的华法林维持剂量明显高于CC型携带者(4．76±0．90) mg·d-1 vs (4．08±1．03) mg· d-1,P=0．04。未发现POR rs2868177与华法林维持剂量存在相关性。结论在中国汉族人工心脏机械瓣膜置换术患者中,POR rs17685 T突变与华法林剂量上调相关,该基因型检测将有助于指导华法林的临床合理应用。
목적탐토POR기인다태성여화법림유지제량적상관성。방법공납입185례중국한족인공심장궤계판막치환술환자,채용 Sequenom MassARRAY? System 검측VKORC1급 POR 상관 SNPs,채용 PCR-RFLP 법검측CYP2C9*3기인형。채용 ANOVA 혹 t검험고찰목적 SNPs여환자화법림유지제량적관계。결과재CYP2C9*1*1휴대자중,POR rs17685 T등위기인휴대자( TT형화CT형)화법림유지제량명현고우 CC 형휴대자(3．50±1．07) mg · d-1 vs (3．14±0．94) mg·d-1,P=0．03。재CYP2C9*1*1급VKORC1 rs9934438 GA/GG휴대자중, POR rs17685 T등위기인휴대자( TT형화CT형)적화법림유지제량명현고우CC형휴대자(4．76±0．90) mg·d-1 vs (4．08±1．03) mg· d-1,P=0．04。미발현POR rs2868177여화법림유지제량존재상관성。결론재중국한족인공심장궤계판막치환술환자중,POR rs17685 T돌변여화법림제량상조상관,해기인형검측장유조우지도화법림적림상합리응용。
Aim To explore the effect of genetic poly-morphisms of POR on the stable warfarin maintenance doses in Han Chinese patients receiving mechanical heart valve replacement. Methods The association between POR gene polymorphisms and warfarin doses of 185 Han Chinese patients were investigated through ANOVA or t test. SNPs of POR and VKORC1 were de-tected by Sequenom? DNA MassArray genotyping method. CYP2C9*3 was genotyped by polymerase chain reaction-restriction fragment length polymorphism method ( PCR-RFLP ) . Patients ’ clinical characteris-tics, INR value and daily dose were obtained from their medical records. Statistical analysis was performed by SPSS 21. 0 software. Results No mutant carriers of POR rs17148944 , POR rs56256515 and rs72553971 were found in this study. The genotype frequencies of other SNPs were in accordance with Hardy-Weinberg e-quilibrium. In the group of patients with CYP2C9*1*1 , the mutant type carriers ( T carriers ) of POR rs17685 had a significantly higher dose than CC carri-ers(3. 50 ± 1. 07) mg·d-1 vs (3. 14 ± 0. 94) mg· d-1,P =0. 03. Also, in the group of patients with CYP2 C9*1*1 and VKORC1 rs9934438 G allele carri-ers, the mutant type carriers ( T carriers ) of POR rs17685 had a significantly higher dose than CC carri-ers(4. 76 ± 0. 90) mg·d-1 vs (4. 08 ± 1. 03) mg· d-1 ,P=0. 04. No significant difference was found in different genotypes of POR rs2868177 . Conclusion These results illustrate that POR rs17685 T carrier is closely associated with a higher warfarin maintenance dose, suggesting that this SNP is useful for clinical guidance of warfarin.