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Polymorphisms of vitamin K-related genes (EPHX1 and VKORC1L1) and stable warfarin doses.

Authors
  • Chung, Jee-Eun1
  • Lee, Kyung Eun2
  • Chang, Byung Chul3
  • Gwak, Hye Sun4
  • 1 School of Pharmacy, Sungkyunkwan University, 2066 Seobu-ro, Suwan si, Gyeonggi-do 16419, Republic of Korea. , (North Korea)
  • 2 College of Pharmacy, Chungbuk National University, 1 Chungdae-ro, Seowon-gu, Cheongju, Chungbuk 28644, Republic of Korea. , (North Korea)
  • 3 Department of Thoracic & Cardiovascular Surgery, Yonsei University Medical Center, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea. , (North Korea)
  • 4 College of Pharmacy and Division of Life and Pharmaceutical Sciences, Ewha Womans University, 52 Ewhayeodae-gil, Seodaemun-gu, Seoul 03760, Republic of Korea. Electronic address: [email protected] , (North Korea)
Type
Published Article
Journal
Gene
Publication Date
Jan 30, 2018
Volume
641
Pages
68–73
Identifiers
DOI: 10.1016/j.gene.2017.10.049
PMID: 29054760
Source
Medline
Keywords
License
Unknown

Abstract

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±2.01mg; 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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