Kuanprasert Srun, Dettrairat Sakchai, Palacajornsuk Poonsub, Kunachiwa Warunee, Phrommintikul Arintaya
Department of Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai 50210, Thailand.
J Med Assoc Thai. 2009 Dec;92(12):1597-601.
Warfarin has been widely used for the prevention and treatment of thromboembolism. Warfarin therapy depends on interaction between physiological, environmental, and genetic factors. Vitamin K epoxide reductase (VKORC1) and cytochrome P450 2C9 (CYP2C9) enzyme conjointly determine the warfarin maintenance dose. The prevalence of CYP2C9 and VKORC1 variants varies among ethnic groups. The purpose of the present study was to investigate the prevalence of CYP2C and VKORC1 in the Northern Thai population.
Patients with valvular heart disease who regularly took a steady maintenance warfarin dose for at least one month were recruited into the present study. Patients who had taken amiodarone or an anti-inflammatory drug were excluded Clinical data were obtained from medical records. Five milliliters of whole blood was drawn from each patient for gene analysis and prothrombin time with international normalized ratio (INR) measurement.
From 242 patients, CYP2C9 *1/*1 was found in 230 patients (95%) and CYP2C9 1/3 was found in 12 patients (5%). Neither mutant CYP2C92 allele nor individuals homozygous for CYP2C93 were observed. Regarding VKORC1, haplotype AB was found in 83 patients (34.3%) and haplotype AA was found in 154 patients (63.6%). Haplotype BB (wild type) was found in five patients (2.1%).
The prevalence of CYP2C9 1/1 is high while the prevalence of CYP2C92 and CYP2C93 is very low. VKORC1 haplotype AA is the most common among the Northern Thai population. Further study regarding pharmacogenetic and non-genetic factors to develop warfarin-dosing algorithm is warranted
华法林已被广泛用于预防和治疗血栓栓塞。华法林治疗取决于生理、环境和遗传因素之间的相互作用。维生素K环氧化物还原酶（VKORC1）和细胞色素P450 2C9（CYP2C9）酶共同决定华法林维持剂量。CYP2C9和VKORC1变体的患病率在不同种族群体中有所不同。本研究的目的是调查泰国北部人群中CYP2C和VKORC1的患病率。
本研究招募了患有瓣膜性心脏病且定期服用稳定维持剂量华法林至少一个月的患者。排除服用胺碘酮或抗炎药的患者。临床数据从医疗记录中获取。从每位患者采集5毫升全血用于基因分析和国际标准化比值（INR）的凝血酶原时间测量。
在242例患者中，230例患者（95%）检测到CYP2C9 *1/*1，12例患者（5%）检测到CYP2C9 1/3。未观察到突变的CYP2C92等位基因，也未发现CYP2C93纯合个体。关于VKORC1，83例患者（34.3%）发现单倍型AB，154例患者（63.6%）发现单倍型AA。5例患者（2.1%）发现单倍型BB（野生型）。
CYP2C9 1/1的患病率较高，而CYP2C92和CYP2C93的患病率非常低。VKORC1单倍型AA在泰国北部人群中最为常见。有必要进一步研究药物遗传学和非遗传因素以制定华法林给药算法。
