日本人ワルファリン服用者でのCYP2C9とVKORC1の遺伝子一塩基多型解析の臨床的意義(岩手医科大学学位審査報告)

• Miyagata You

  Division of Oral Surgery, Faculty of Dentistry, Iwate Medical University

• Nakai Kenji

  Internal Medicine of Dentistry, Faculty of Dentistry, Iwate Medical University

• Sugiyama Yoshiki

  Division of Oral Surgery, Faculty of Dentistry, Iwate Medical University

書誌事項

タイトル別名

• Clinical Significance of Combined CYP2C9 and VKORC1 Genotypes in Japanese Patients Requiring Warfarin

抄録

The individual management of anticoagulation therapy is important for safe medical outcomes, including those of oral surgery. Here, Japanese patients who received warfarin (n = 35) and normal controls (n = 125) were analyzed by real-time PCR to determine the frequencies of single nucleotide polymorphisms in VKORC1 (vitamin K epoxide reductase complex, subunit 1) and CYP2C9 and how these frequencies related to warfarin dose and PT-INR. The genetic polymorphisms CYP2C9^*2 (416 C > T), CYP2C9^*3 (1061 A > C), and intron 1-136 C > T in VKORC1 (1173 C > T) were measured. All patients had the wild-type CYP2C9 gene (*1/*1). All 160 cases had the wild-type (CC) type CYP2C9^*2, 93.8% had AA type CYP2C9^*3, 6.2% had AC type CYP2C9^*3, 1.2% had CC type VKORC1, 13.8% had CT type VKORC1, and 85% had TT type VKORC1. The CC type VKORC1 genetic polymorphism was associated with a significantly higher mean warfarin maintenance dose (4.5 ± 0.5 mg) than other VKORC1 genotypes (TT type 2.9 ± 0.1 mg: CT type 3.4 ± 0.3 mg). Categorization of the patients in terms of the combined CYP2C9 and VKORC1 haplotype (the warfarin-responsive index; WRI) revealed the mean daily warfarin maintenance dose was 3.0 ± 0.1 mg for WRI 1 and 3.7 ± 0.3 mg for WRI 2 (P < 0.012). The event survey revealed 2 patients with nonfatal cerebral hemorrhage had a WRI score of 2 (VKORC1 C/T heterozygosity genotype). Thus, CYP2C9 and VKORC1 haplotype analysis allows prediction of warfarin maintenance dosage. The findings may provide a personalized use of warfarin in the field of oral surgery.

収録刊行物

• International Heart Journal

  International Heart Journal 52 (1), 44-49, 2011

  一般社団法人 インターナショナル・ハート・ジャーナル刊行会

キーワード

• Genotype
• CYP2C9
• VKORC1
• Warfarin
• Japanese
• Individual therapy

詳細情報

• CRID: 1390282680201984384
• NII論文ID: 130000410639
• NII書誌ID: AN00017474
• DOI: 10.1536/ihj.52.44
• ISSN: 13493299
• ISSN: 13492365
• Web Site: http://id.nii.ac.jp/1181/00002038/
• Web Site: http://www.jstage.jst.go.jp/article/ihj/52/1/52_1_44/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2011323142
• 本文言語コード: en
• データソース種別:
  • JaLC
  • IRDB
  • Crossref
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可