Polymorphisms of vitamin K-related genes (EPHX1 and VKORC1L1) and stable warfarin doses
- 주제(키워드) Epoxide hydrolase 1 , VKORC1L1 , Vitamin K cycle , Genetic polymorphism , Stable warfarin doses , Number needed to genotype
- 주제(기타) Genetics & Heredity
- 설명문(일반) [Chung, Jee-Eun] Sungkyunkwan Univ, Sch Pharm, 2066 Seobu Ro, Suwan Si 16419, Gyeonggi Do, South Korea; [Lee, Kyung Eun] Chungbuk Natl Univ, Coll Pharm, 1 Chungdae Ro, Cheongju 28644, Chungbuk, South Korea; [Chang, Byung Chul] Yonsei Univ, Med Ctr, Dept Thorac & Cardiovasc Surg, 50-1 Yonsei Ro, Seoul 03722, South Korea; [Gwak, Hye Sun] Ewha Womans Univ, Coll Pharm, 52 Ewhayeodae Gil, Seoul 03760, South Korea; [Gwak, Hye Sun] Ewha Womans Univ, Div Life & Pharmaceut Sci, 52 Ewhayeodae Gil, Seoul 03760, South Korea
- 등재 SCIE, SCOPUS
- 발행기관 ELSEVIER SCIENCE BV
- 발행년도 2018
- URI http://www.dcollection.net/handler/ewha/000000150106
- 본문언어 영어
- Published As http://dx.doi.org/10.1016/j.gene.2017.10.049
초록/요약
The aim of this study was to investigate the possible effects of EPHX1 and VKORC1L1 polymorphisms on variability of responses to warfarin. Sixteen single nucleotide polymorphisms (SNPs) in 201 patients with stable warfarin doses were analyzed including genes of VKORC1, CYP2C9, CYP4F2, GGCX, EPHX1 and VKORC1L1. Univariate analysis was conducted for the association of genotypes with stable warfarin doses. Multiple linear regression analysis was used to investigate factors that independently affected the inter-individual variability of warfarin dose requirements. The rs4072879 of VKORC1L1 (A > G) was significantly associated with stable warfarin doses; wild homozygote carriers (AA) required significantly lower stable warfarin doses than those with the variant G allele (5.02 +/- 1.56 vs. 5.96 +/- 2.01 mg; p = 0.001). Multivariate analysis showed that EPHX1 rs1877724 and VKORC1L1 rs4072879 accounted for 1.5% and 1.3% of the warfarin dose variability. Adding EPHX1 and VKORC1L1 SNPs to the base model including non-genetic variables (operation age, body weight and the therapy of ACEI or ARB) and genetic variables (VKORC1 rs9934438, CYP2C9 rs1057910, and CYP4F2 rs2108622) gave a number needed to genotype of 34. This study showed that polymorphisms of EPHX1 and VKORC1L1 could be determinants of stable warfarin doses.
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