A Two-Stage Matched Case-Control Study on Multiple Hypertensive Candidate Genes in Han Chinese
A Two-Stage Matched Case-Control Study on Multiple Hypertensive Candidate Genes in Han Chinese
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DOI：
10.1038/ajh.2012.44
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发表时间：
2012-07-01
影响因子：
3.2
通讯作者：
Pan, Wen-Harn
中科院分区：
文献类型：
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作者：
Kuo, Tai-Yue;Kang, Mei-Jyh;Pan, Wen-Harn
背景：全世界约有1/3的成年人患有高血压，台湾为380万，中国为1.6亿，全球为10亿。它是导致中风、心血管疾病和终末期肾脏疾病的主要危险因素。每年，全世界有1350多万人死于与高血压有关的疾病。方法利用992例台湾汉族青年高血压患者和992例对照者的单核苷酸多态性（snp）基因型数据，对高血压进行两期相关性研究。研究了36个具有重要功能的高复制高血压候选基因的238个snp。采用条件逻辑回归进行关联分析。结果：我们发现了两个snp与第一阶段和第二阶段的高血压密切相关。第一个SNP （rs2301339）位于鸟嘌呤核苷酸结合蛋白β 3亚基（GNB3），另一个SNP （rs17254521）位于胰岛素受体（INSR）。结论sssnp rs2301339与C825T （rs5443）在连锁不平衡（LD）中完全相关，C825T与高加索人高血压有关，但在亚洲人群中不一致。然而，我们发现在我们的样本中，这个SNP与之前的研究结果相反。总之，本研究确定了GNB3中一个新的SNP和INSR中一个新的SNP，它们与年轻发病的高血压密切相关。由于样本量相对较小，结果仍应谨慎解释，并需要在其他研究中重复。
BACKGROUNDHypertension affects about 1/3 of adults worldwide, similar to 3.8 million in Taiwan, 160 million in China, and 1 billion worldwide. It is a major risk factor leading to stroke, cardiovascular disease, and end-stage renal disease. In each year, more than 13.5 million deaths are due to hypertension-related diseases worldwide.METHODSWe performed a two-stage association study of hypertension using genotype data of single-nucleotide polymorphisms (SNPs) from 992 young-onset hypertensive cases and 992 matched controls of Han Chinese in Taiwan. A total of 238 SNPs of 36 highly replicated hypertension candidate genes with functional importance were investigated. Association analysis was carried out using conditional logistic regression.RESULTSWe identified two SNPs that were strongly associated with hypertension in both the first and the second stages. The first SNP (rs2301339) is located at guanine nucleotide-binding protein beta 3 subunit (GNB3) and the other one (rs17254521) is located at insulin receptor (INSR).CONCLUSIONSSNP rs2301339 is perfectly linked in linkage disequilibrium (LD) with C825T (rs5443) which has been associated with hypertension in Caucasian, but inconsistent in Asian populations. However, we found that in our sample this SNP has an opposite effect with the previous findings. In summary, this study identified one novel SNP in GNB3 and one novel SNP in INSR that are strongly associated with young-onset hypertension. Due to relatively small sample size, the results should still be interpreted with caution and need to be replicated in other studies.