Pharmacogenetic effects of 'candidate gene complexes' on stroke in the GenHAT study.
Pharmacogenetic effects of 'candidate gene complexes' on stroke in the GenHAT study.
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GenHAT 研究中“候选基因复合物”对中风的药物遗传学影响。
DOI：
10.1097/fpc.0000000000000088
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发表时间：
2014
影响因子：
2.6
通讯作者：
Arnett,DonnaK
中科院分区：
文献类型：
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作者：
Sørensen,IzelF;Vazquez,AnaI;Irvin,MargueriteR;Sørensen,Peter;Davis,BarryR;Ford,CharlesE;Boerwinkle,Eric;Eckfeldt,JohnH;Arnett,DonnaK
目的本研究的目的是探讨在使用三种降压药物之一氯噻酮、氯噻酮、氯噻酮和氯噻酮治疗的脑卒中患者中是否存在基因型与治疗的相互作用。参与者和方法在GenHAT研究中经历过中风的436名非洲裔美国人和539名白人中，对768个单核苷酸多态性（SNP）进行基因分型。280个候选基因为了检测基因型与治疗的相互作用，我们使用Pearson χ 2检验来评估三个药物治疗组在单个SNP水平上的基因型频率是否不同。从这些单SNP分析中，我们得出了基因和基因复合体水平上关联程度的汇总统计量。这是通过使用基因位置信息对SNP进行分组并基于蛋白质-蛋白质相互作用定义基因复合物来完成的。为了评估所观察到的检验统计量的统计学意义，我们得出了一个经验P值，通过模拟数据下的零hypothes.Results我们发现，在患者谁经历过中风，有一个显着的遗传差异高血压药物治疗组。在非裔美国人中，SNP rs 12143842与药物治疗显著相关（P< 0.001）。在基因水平上，非裔美国人的HNRNPA 1 P4和NOS 1AP以及非西班牙裔白人的PRICKLE 1和NINJ 2与药物治疗显著相关（P< 0.01），而检测的基因复合体均未显示出显著性差异。结论根据药物治疗组间的遗传差异，我们得出结论，某些基因型与脑卒中患者的降压治疗可能存在相互作用。这需要在其他研究中重复。
Objective The aim of this study was to investigate whether there is a genotype-by-treatment interaction in patients experiencing stroke and treated with one of three antihypertensive drugs, that is chlorthalidone, amlodipine, or lisinopril.Participants and methods A population of 436 African Americans and 539 whites who had experienced stroke in the GenHAT study were genotyped for 768 single nucleotide polymorphisms (SNPs) in 280 candidate genes. To detect a genotype-by-treatment interaction, we used the Pearson’s χ 2-test to assess whether the genotype frequencies differed at the single SNP level for the three drug treatment groups. From these single SNP analyses, we derived a summary statistic for the degree of association at the gene and gene complex levels. This was done by grouping SNPs using information on gene locations and defining gene complexes on the basis of protein–protein interactions. To assess the statistical significance of the observed test statistic, we derived an empirical P-value by simulating data under the null hypothesis.Results We found that, in patients who have experienced stroke, there is a significant genetic difference between hypertension drug treatment groups. In African Americans, SNP rs12143842 showed a significant association (P< 0.001) with drug treatment. At the gene level, HNRNPA1P4 and NOS1AP in African Americans and PRICKLE1 and NINJ2 in non-Hispanic whites were significantly associated (P< 0.01) with drug treatment, whereas none of the gene complexes tested showed significance.Conclusion On the basis of the genetic differences between drug treatment groups, we conclude that there may be an interaction between certain genotypes and antihypertensive treatment in stroke patients. This needs to be replicated in other studies.