Correlation between CYP2C9, APOE gene polymorphisms and stable warfarin and model prediction dose_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

CHENG Xian ,  BAI Shutang

The Second Department of Cardiothoracic Surgery, Haikou Hospital, Central South University Xiangya School of Medicine, Haikou, 570208, P.R.China;

Corresponding?author：

BAI Shutang, Email: cxxpop@163.com

Keywords：

Warfarin dose; CYP2C9; APOE; model prediction

DOI：

10.7507/1007-4848.201810012

Video：

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Objective To investigate the effect of CYP2C9 and APOE on the dose of stable warfarin and model prediction in Hainan population.Methods From August 2016 to July 2018, 368 patients who required heart valve replacement and agreed to take warfarin anticoagulation at the second department of cardiothoracic surgery in our hospital were enrolled, including 152 males aged 48.5–70.5 (60.03±10.18) years and 216 females aged 43.5–65.6 (54.24±11.35) years. CYP2C9 and APOE were amplified by polymerase chain reaction. The gene fragment was sequenced by the Single Nucleotide Polymorphisms (SNP) site. The patients' age, sex, weight, history of smoking and drinking, and the dose of stable warfarin were recorded. Regression analysis of these clinical data was made to construct a dose prediction model.Results Among 368 patients, CYP2C9 genotype test results showed 301 patients (81.8%) with *1*1 genotype, and 67 patients (18.2%) with *1*3 type. For different CYP2C9 genotype patients, the difference was statistically significant in the dose of stable warfarin (P<0.05). The results of APOE genotype showed 93 patients (25.3%) with E2 genotype, 221 patients (60.1%) with E3 genotype, and 54 patients (14.7%) with E4 genotype; the dose of stable warfarin in patients with different APOE genotypes was statistically significant (P<0.05). Multiple regression analysis showed that patients' age, body weight, and CYP2C9 and APOE genotypes were correlated with the dose of stable warfarin. The correlation coefficient R² was 0.572, and the prediction model was statistically significant (P<0.05).Conclusion CYP2C9 and APOE gene polymorphisms exist in Hainan population. There is significant difference in the dose of stable warfarin among different genotypes of patients. The model to predict stable warfarin can partly explain the difference of warfarin among different patients.

Citation： CHENG Xian, BAI Shutang. Correlation between CYP2C9, APOE gene polymorphisms and stable warfarin and model prediction dose. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2019, 26(6): 543-547. doi: 10.7507/1007-4848.201810012 Copy

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1. 伍建國, 戴明, 唐鎧, 等. 心臟瓣膜置換術后華法林抗凝治療效果研究. 中國臨床研究, 2015, 28(11): 1450-1452.
2. 顧永麗, 葛衛紅, 于鋒. 心臟瓣膜置換術后患者華法林抗凝治療的藥學監護. 中國醫院藥學雜志, 2013, 33(11): 911-913.
3. 婁瑩, 謝爽, 劉紅, 等. CYP2C9 基因多態性對中國心臟機械瓣置換患者華法林初始抗凝效果的影響. 中國臨床藥理學雜志, 2013, 29(1): 3-5.
4. 婁瑩, 韓璐璐, 李彥, 等. 六種基因多態性對中國漢族人群華法林穩定劑量的影響. 中華醫學遺傳學雜志, 2014, 31(3): 367-371.
5. 馬曉迎, 張健. 老年非瓣膜病心房顫動患者的抗凝治療. 中華老年多器官疾病雜志, 2015, 14(3): 236-240.
6. 張喆, 羅夢林, 田敏, 等. 華法林抗凝患者的抗凝現狀調查及分析. 中國醫院藥學雜志, 2014, 34(2): 127-130.
7. 柯鹍鵬, 劉寅強, 楊鴻生. 華法林抗凝劑量與其影響因素的研究進展. 醫學綜述, 2013, 19(11): 2055-2058.
8. 龔金龍, 吳婷竹, 曹松臻, 等. 非瓣膜病房顫患者華法林抗凝治療的現狀. 實用老年醫學, 2015, 29(8): 646-648.
9. 鄭必龍, 劉俊. 華法林抗凝血作用及影響因素分析. 安徽醫藥, 2013, 17(11): 1975-1977.
10. Dai DP, Xu RA, Hu LM, et al. CYP2C9 polymorphism analysis in Han Chinese populations: building the largest allele frequency database. Pharmacogenomics J, 2014, 14(1): 85-92.
11. Higashi MK, Veenstra DL, Kondo LM, et al. Association between CYP2C9 genetic variants and anticoagulation-related outcomes during warfarin therapy. JAMA, 2002, 287(13): 1690-1698.
12. 馮頻頻, 彭文星, 石秀錦, 等. 基因多態性對華法林劑量影響的研究進展. 中國藥房, 2017, 28(11): 1581-1584.
13. Kohnke H, S?rlin K, Granath G, et al. Warfarin dose related to apolipoprotein E (APOE) genotype. Eur J Clin Pharmacol, 2005, 61(5-6): 381-388.
14. Kimmel SE, Christie J, Kealey C, et al. Apolipoprotein E genotype and warfarin dosing among Caucasians and African Americans. Pharmacogenomics J, 2008, 8(1): 53-60.
15. 黃盛文, 向道康, 吳海麗, 等. 五種基因多態性對華法林用量個體差異影響的研究. 中華醫學遺傳學雜志, 2011, 28(6): 661-665.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Correlation between CYP2C9, APOE gene polymorphisms and stable warfarin and model prediction dose

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