A Haplotype-Based Case-Control Study Examining Human Extracellular Superoxide Dismutase Gene and Essential Hypertension
A Haplotype-Based Case-Control Study Examining Human Extracellular Superoxide Dismutase Gene and Essential Hypertension
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DOI：
10.1291/hypres.31.1533
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发表时间：
2008-08-01
影响因子：
5.4
通讯作者：
Usami, Ron
中科院分区：
文献类型：
--
作者：
Naganuma, Takahiro;Nakayama, Tomohiro;Usami, Ron
研究表明，氧化应激参与了原发性高血压（EH）的病理生理过程，EH是一种多因素疾病。细胞外超氧化物歧化酶（EC-SOD）通过将有毒的超氧阴离子（O-2（-））转化为毒性较小的过氧化氢（H2 O2）来保护人体免受氧化应激。在EC-SOD敲除小鼠中，据报道血压显著高于野生型小鼠。因此，本研究的目的是通过单核苷酸多态性（SNPs）的单倍型为基础的病例对照研究，探讨EH和人类EC-SOD基因的关系。我们选择EC-SOD基因内的6个SNPs（rs 13306703、rs699473、rs699474、rs 17881426、rs 2536512和rs 1799895），然后在243例EH患者和251例年龄匹配的正常血压（NT）受试者中进行病例对照研究。在日本受试者中，没有发现rs699474的异质性，并且在EH和NT组之间没有观察到每个SNP的基因型或等位基因的总体分布的显著差异。然而，在使用rs 13306703和rs 2536512的基于单倍型的病例对照研究中，在总体分布中观察到显著差异（chi（2）=14.26，p=0.003）。EH组T-A单倍型频率显著高于NT组（2.4% vs. 0.0%，p
It has been reported that oxidative stress is involved in the pathophysiology of essential hypertension (EH), which is a multifactorial disorder. Extracellular superoxide dismutase (EC-SOD) protects the human body from oxidative stress by converting the toxic superoxide anion (O-2(-)) into less toxic hydrogen peroxide (H2O2). In EC-SOD knockout mice, blood pressure was reported to be significantly higher than that seen in wild-type mice. The aim of this study was thus to investigate the relationship between EH and the human EC-SOD gene by using single-nucleotide polymorphisms (SNPs) in a haplotype-based case-control study. We selected 6 SNPs within the human EC-SOD gene (rs13306703, rs699473, rs699474, rs17881426, rs2536512 and rs1799895), and then performed case-control studies in 243 EH patients and 251 age-matched normotensive (NT) subjects. In Japanese subjects, no heterogeneity was found for rs699474, and no significant differences were observed between the EH and NT groups for the overall distribution of the genotypes or the alleles for each of the SNPs. However, in the haplotype-based case-control study that used rs13306703 and rs2536512, significant differences were observed in the overall distribution (chi(2)=14.26, p=0.003). The frequency of the T-A haplotype was significantly higher in the EH group than in the NT group (2.4% vs. 0.0%, p