Hypertension-susceptibility gene prevalence in the Pacific Islands and associations with hypertension in Melanesia
Hypertension-susceptibility gene prevalence in the Pacific Islands and associations with hypertension in Melanesia
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DOI：
10.1038/jhg.2012.147
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发表时间：
2013-03-01
影响因子：
3.5
通讯作者：
Ohashi, Jun
中科院分区：
文献类型：
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作者：
Furusawa, Takuro;Naka, Izumi;Ohashi, Jun
人类原发性高血压部分由遗传因素引起。血管紧张素原（AGT）、G蛋白β 3亚基（GNB 3）和细胞色素P450 3A 5（CYP 3A 5）是高血压的候选易感基因，这些基因座上的危险等位基因被认为是由于人类适应非洲以外的气候变化而产生的。本研究旨在揭示太平洋岛屿人群中高血压易感基因型的频率以及这些单核苷酸多态性（SNPs）与高血压的关联。在编码AGT（rs699、rs 5049和rs 5051）、GNB 3（rs 5443）和CYP 3A 5 *1/*3（rs776746）的基因中的SNP对来自美拉尼西亚、波利尼西亚和波利尼西亚人群的804个个体进行基因分型。对383名美拉尼西亚所罗门岛民进行了这些SNP与高血压之间的关联性测试。我们发现在美拉尼西亚所罗门岛民中rs 5049的A/A基因型是高血压的危险因素（P = 0.025）; AGT的三个SNPs处于连锁不平衡。rs699，rs 5051和rs776746的祖先等位基因，以及rs 5443的衍生等位基因在这里调查的人群中的频率在其他赤道人群。虽然与高血压和其他人口有关的其他多态性仍有待研究，但这些研究结果表明，太平洋岛民对高血压的易感性是由于人类移徙和适应而产生的。Journal of Human Genetics（2013）58，142-149; doi：10.1038/jhg.2012.147; 2013年1月17日在线发表
Human essential hypertension is partly caused by genetic factors. Angiotensinogen (AGT), G-protein beta 3-subunit (GNB3) and cytochrome P450 3A5 (CYP3A5) are candidate hypertension susceptibility genes and risk alleles at these loci have been thought to arise owing to human adaptation to climatic changes following the migration out-of-Africa. This study aimed to reveal the frequencies of hypertension-susceptibility genotypes in Pacific Island populations and associations of these single-nucleotide polymorphisms (SNPs) to hypertension. Genotyping was conducted for 804 individuals from Melanesian, Micronesian and Polynesian populations at SNPs in the genes encoding AGT (rs699, rs5049 and rs5051), GNB3 (rs5443) and CYP3A5*1/*3 (rs776746). Associations between these SNPs and hypertension were tested for 383 Melanesian Solomon Islanders. We found that the A/A genotype at rs5049 was a risk factor for hypertension (P = 0.025) in the Melanesian Solomon Islanders; three SNPs for AGT were in linkage disequilibrium. The ancestral alleles of rs699, rs5051 and rs776746, and the derived allele of rs5443 were as frequent in the populations surveyed here as in other equatorial populations. Although other polymorphisms associated with hypertension and additional populations remain to be studied, these findings suggest that the Pacific Islanders' susceptibility to hypertension arose because of human migration and adaptation. Journal of Human Genetics (2013) 58, 142-149; doi:10.1038/jhg.2012.147; published online 17 January 2013