东亚群体中高血压GWAS阳性9个SNP在中国傣族及蒙古族群体中的验证研究

The replocation study of association between hypertension and 9 GWAS positive SNPs which were found in East Asia populations in Chinese Dai and Mongolian people

目的为了验证GWAS研究发现的3个高血压一个基因的相关性。方法本研究选取了3个在东亚群体中被GWAS研究证实了与高血压发生相关的基因(AKAP13,ENPEP和CNNM2)上的9个SNP,在傣族和蒙古族群体中进行验证。对这9个SNPs用SNaPshot的方法在774例傣族群体和409例蒙古族群体中进行了分型,排布单倍型并进行了统计学分析。结果发现统计学上无法证明这9个SNPs与高血压相关。但是在ENPEP基因的一连锁区段中,rs1126483在傣族群体中呈现与收缩压升高弱阳性关联(χ2=4.53,P=0.033)。同时rs3796889在蒙古族群体中也与收缩压的升高呈现弱阳性关联(χ2=4.35,P=0.037)。虽然这一阳性在进行统计学矫正后消失。结论本研究同时在起源不同,生活环境均差异较大的两个群体中均观察到ENPEP基因这一区段与高血压的关联,这也许暗示了此基因确实可能与高血压发生相关。另一方面本研究的阴性结果,也暗示了中国一些相对封闭的群体可能具有更窄的高血压遗传变异谱。

Objective： In order to verify the association between the 3 GWAS positive genes and Hypertension. Methods： The 9 SNPs on three GWAS positive gene （AKAP13, ENPEP and CNNM2） were chosen to replicate in Chinese Dai and Mongolian people in this study. These 9 SNPs were genotyped in 774 Dai and 409 Mongolian people by SNaPshot technology. After getting the genotypes and haplotypes, the statistical tests were performed. Results： The data showed that there are no statistical associations between these 9 SNPs and hypertension. But two SNPs in a linkage block of ENPEP gene show weak positive association with hypertension. One is rs1126483 which associated with the increase in systolic blood pressure （SBP） in Dai people （χ2=4.53, P=0.033） . The other one is rs3796889 which associated with the increase in SBP in Mongolian people （χ2=4.35, P=0.037） . Although these weak associations were disappeared after Bonferroni correction, the associations happened in both populations which have different origins and distinct living environments. Conclusion： It may be implied that mutations in ENPEP are likely to cause the hypertension. On the other side, our negative association results also suggest that some ethnic groups of China maybe have narrow genetic mutation spectrum which could induce the hypertension.