Journal of Chinese Pharmaceutical Sciences ›› 2016, Vol. 25 ›› Issue (9): 683-689.DOI: 10.5246/jcps.2016.09.076

• Original articles • Previous Articles     Next Articles

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

Yatong Zhang1*, Xi Liang2, Fan Dong1, Zihui Zheng1, Xin Hu1   

  1. 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
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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

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