Do genetic defects of DNA repair relevant proteins alter susceptibility to hypertension? A case–control study in northeastern Han Chinese

• Oxidative stress plays a causal role in the molecular processes leading to hypertension, and we therefore formulate a hypothesis that genetic defects of proteins that involve in DNA repair mechanisms might entail a potential risk for hypertension.
• Our most noteworthy finding was a contributory role of XRCC1 gene rs25487 variant in the development of hypertension, following a recessive inherited pattern.
• This is the first report assessing the susceptibility of genetic defects in DNA repair relevant genes to hypertension in Chinese.
• This study highlights the complexity of genetic variation on disease risk, and provides evidence supporting the logical role of DNA repair relevant genes in the pathogenesis of hypertension.

The aim of this study was to examine the individual and interactive associations of five non-synonymous variants of four DNA repair relevant genes (XRCC1, XRCC3, hOGG1, NQO1) with hypertension in a large northeastern Han Chinese population. This was a hospital-based study involving 1009 hypertensive patients and 756 normotensive controls. All five variants satisfied the Hardy–Weinberg equilibrium. With a Bonferroni corrected alpha of 0.05/5, significance was only attained in the genotype (P = 0.007) and allele (P = 0.006) distributions of rs25487 in XRCC1 gene between patients and controls, with its mutant allele conferring 29% (95% CI: 1.09–1.53; P = 0.003), 31% (95% CI: 1.05–1.62; P = 0.015) and 66% (95%CI: 1.10–2.52; P = 0.016) increased risks of hypertension under the additive, dominant and recessive models, respectively after adjusting for confounders. The frequency of allele combination C-A-C-G-C (alleles in order of rs1799782, rs25487, rs861539, rs1052133 and rs1800566) was significantly higher in patients than in controls (P = 0.003), while that of C-G-C-C-C was significantly lower (P = 0.001). Interaction analysis failed to identify any suggestive evidence of synergism across five examined variants. Our findings provide evidence for a contributory role of XRCC1 gene rs25487 variant in the development of hypertension, and this variant possibly acted in a recessive pattern.