利用外显子组芯片研究常见和罕见基因变异对非裔美国人和欧裔美国人华法林剂量的影响。
Influence of common and rare genetic variation on warfarin dose among African-Americans and European-Americans using the exome array.
作者信息
Liu Nianjun, Irvin Marguerite R, Zhi Degui, Patki Amit, Beasley T Mark, Nickerson Deborah A, Hill Charles E, Chen Jinbo, Kimmel Stephen E, Limdi Nita A
机构信息
Department of Epidemiology & Biostatistics, School of Public Health - Bloomington, Indiana University, Bloomington, IN 47405, USA.
Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
出版信息
Pharmacogenomics. 2017 Jul;18(11):1059-1073. doi: 10.2217/pgs-2017-0046. Epub 2017 Jul 7.
AIM
We conducted a genome-wide association study using the Illumina Exome Array to identify coding SNPs that may explain additional warfarin dose variability.
PATIENTS & METHODS: Analysis was performed after adjustment for clinical variables and genetic factors known to influence warfarin dose among 1680 warfarin users (838 European-Americans and 842 African-Americans). Replication was performed in an independent sample.
RESULTS
We confirmed the influence of known genetic variants on warfarin dose variability. Our study is the first to show the association between rs12772169 and warfarin dose in African-Americans. In addition, genes COX15 and FGF5 showed significant association in European-Americans.
CONCLUSION
We identified some novel genes/SNPs that underpin warfarin dose response. Further replication is needed to confirm our findings.
目的
我们使用Illumina外显子组芯片进行了一项全基因组关联研究，以识别可能解释华法林剂量额外变异性的编码单核苷酸多态性（SNP）。
患者与方法
对1680名华法林使用者（838名欧裔美国人及842名非裔美国人）进行分析，分析时对已知会影响华法林剂量的临床变量和遗传因素进行了校正。在一个独立样本中进行了重复验证。
结果
我们证实了已知遗传变异对华法林剂量变异性的影响。我们的研究首次显示了rs12772169与非裔美国人华法林剂量之间的关联。此外，COX15和FGF5基因在欧裔美国人中显示出显著关联。
结论
我们识别出了一些支撑华法林剂量反应的新基因/单核苷酸多态性。需要进一步重复验证以证实我们的发现。
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