中国心血管病患者中STX4 基因多态性对华法林作用的影响

doi:10.5246/jcps.2016.09.076

中国药学(英文版) ›› 2016, Vol. 25 ›› Issue (9): 683-689.DOI: 10.5246/jcps.2016.09.076

中国心血管病患者中STX4 基因多态性对华法林作用的影响

张亚同^1*, 梁欣², 董凡¹, 郑子恢¹, 胡欣¹

1. 北京医院国家老年医学中心药学部, 北京 100730
2. 北京潞河医院药剂科, 北京 101149

收稿日期:2016-04-21 修回日期:2016-05-20 出版日期:2016-09-28 发布日期:2016-05-28
通讯作者: Tel.: +86-010-85133637, E-mail: zyt2002888@qq.com

The effect of polymorphisms in STX4 on Warfarin dosage in Chinese cardiovascular disease patients

Yatong Zhang^1*, Xi Liang², Fan Dong¹, Zihui Zheng¹, Xin Hu¹

1. Department of Pharmacy, National Center of Gerontology, Beijing Hospital, Beijjing 100730, China
2. Department of Pharmacy, Beijing Luhe Hospital, Tongzhou, Beijing 101149, China

Received:2016-04-21 Revised:2016-05-20 Online:2016-09-28 Published:2016-05-28
Contact: Tel.: +86-010-85133637, E-mail: zyt2002888@qq.com

摘要/Abstract

摘要：

既往研究证实VKORC1和CYP2C9多态性对华法林的抗凝作用影响较大, 但是其它常见遗传变异性对华法林常规剂量影响仍不明确。本研究目标是调查其他候选基因(CYP4F2, CACNA1C, STX4)单核苷酸多态性(SNPs)对中国心血管疾病患者日常华法林稳定剂量(DWMD)的影响。北京医院207名应用华法林的心血管疾病患者纳入研究, 用药后一天抽血并提取全血DNA, 应用LDR(连接酶检测反应)方法检测5个基因VKORC1, CYP2C9, CYP4F2, CACNA1C和STX4的9个SNPs(rs9923231, rs9934438, rs7294, rs1799853, rs1057910, rs4086116, rs2108622, rs216013, rs10871454), 应用单因素分析和多重线性回归分析来分析SNP和其他因素(包括体表面积, 合并他汀类药物等变量)与DWMD的关系。4个位点(CYP2C9基因的rs9923231, rs9934438, rs7294和STX4基因的rs10871454)对DWMD有显著影响。多元线性回归模型显示, STX4基因的rs10871454, BSA, 合并他汀类药物和CYP2C9的rs1057910对DWMD的影响最显著并进入最后的公式。并且在所有基因位点中STX4上的rs10871454对华法林的剂量影响最大, 这表明它可作为预测中国患者的华法林稳定剂量的关键基因因素。

关键词: 华法林, STX4, VKORC1, CYP2C9, 他汀类药物

Abstract:

VKORC1 and CYP2C9 have been shown to be strongly associated with Warfarin dosing. However, it is still unclear whether other common genetic variants also contribute to the variation in Warfarin dosing. In the present study, we aim to investigate possible effects of single nucleotide polymorphisms (SNPs) in other candidate genes (CYP4F2, CACNA1C and STX4), as well as several factors, on stable daily Warfarin dosage (DWMD) in Chinese cardiovascular disease patients. 207 cardiovascular disease patients treated with Warfarin were recruited from Beijing Hospital. DNA was extracted from the blood samples collected one day after Warfarin administration. Nine SNPs (i.e. rs9923231, rs9934438, rs7294, rs1799853, rs1057910, rs4086116, rs2108622, rs216013 and rs10871454 in five genes (i.e. VKORC1, CYP2C9, CYP4F2, CACNA1C and STX4) were analyzed using ligase detection reactions (LDR). Univariate analyses and multiple linear regression analyses were performed to analyze the associations between SNPs and other factors (i.e. body surface area (BSA), Statin medication) and DWMD. Four SNPs (i.e. rs9923231, rs9934438, rs7294 in VKORC1 and rs10871454 in STX4) had significant statistically effects on DWMD. The multiple linear regression model showed that rs10871454 in STX4, BSA, statin medication, and rs1057910 in CYP2C9 were the significant independent covariates of DWMD. SNP (rs10871454) in STX4 had the strongest effect on Warfarin dosing among the examined candidate genes, indicating that it might serve as a key genetic factor for prediciting the Warfarin maintenance dose in Chinese patients.

Key words: Warfarin, STX4, VKORC1, CYP2C9, Statin

中图分类号:

R961

Supporting:

张亚同, 梁欣, 董凡, 郑子恢, 胡欣. 中国心血管病患者中STX4 基因多态性对华法林作用的影响[J]. 中国药学(英文版), 2016, 25(9): 683-689.

Yatong Zhang, Xi Liang, Fan Dong, Zihui Zheng, Xin Hu. The effect of polymorphisms in STX4 on Warfarin dosage in Chinese cardiovascular disease patients[J]. Journal of Chinese Pharmaceutical Sciences, 2016, 25(9): 683-689.

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中国心血管病患者中STX4 基因多态性对华法林作用的影响

The effect of polymorphisms in STX4 on Warfarin dosage in Chinese cardiovascular disease patients

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