A Haplotype-Based Case-Control Study Examining Human Extracellular Superoxide Dismutase Gene and Essential Hypertension

Abstract

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 (O2 -) 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 (

Polymorphisms of antioxidant enzymes, blood pressure and risk of hypertension

“…In the present study, the trend observed in the general population became more evident when only hypertensive patients were considered and the large differences in BP observed were replicated in the other population of hypertensive patients. Furthermore, the polymorphism rs2536512 had been previously reported associated with an increased risk for HTN in other populations [19,20], which reinforces our findings.…”

“…Moreover, the possible influence of common genetic variants of genes codifying for the main antioxidant enzymes has been previously explored in a few studies with discordant results. A single nucleotide polymorphism, c.172G>A (rs2536512), of the extracellular superoxide dismutase (SOD3) has been associated with an increased risk for HTN [19,20]. Furthermore, two polymorphisms in the promoter region of the catalase gene (CAT), c.-844A>G (rs769214) and c.-262T>C [21,22], and one singlenucleotide polymorphism (SNP) of the glutathione peroxidase 1 gene, c.599C>T (rs1050450), have been linked to higher values of BP, but not to elevated risk for HTN [23].…”

Relationships between single nucleotide polymorphisms of antioxidant enzymes and disease

“…The genotype frequencies of the six SOD3 SNPs are similar in hypertensive subjects and normotensive controls. However, the rs13306703 and rs2536512 mutations are associated with essential hypertension (Naganuma et al, 2008). Two of the SOD3 SNPs present in exon 2, rs1799895 and rs2536512, are A > G missense mutations, whereas another is present in intron 1, rs17881426, and substitutes A > T. The other three SNPS are in the 5′ region: rs13306703, a C > T substitution; rs699474, an A > C/G substitution, and rs699473, which is also a C > T substitution.…”

Purinergic receptor P2Y, G-protein coupled, 2 (P2RY2) gene is associated with cerebral infarction in Japanese subjects

“…Differences in the distributions of genotypes and alleles between the CI patients and controls were analyzed using Fisher's exact test. On the basis of the genotype data of the genetic variations, we performed linkage disequilibrium analysis and haplotype-based case-control analysis, using the expectation maximization algorithm 17 and the software SNPAlyze version 3.2 (Dynacom, Yokohama, Japan). Pairwise linkage disequilibrium analysis was performed using five SNPs.…”