Association of rs2271037 and rs3749585 polymorphisms in CORIN with susceptibility to hypertension in a Chinese Han population: A case-control study

摘要

Corins are membrane-bound protease that regulates blood pressure by activating the natriuretic peptides. These pro-atrial natriuretic peptide convertases are essential for sodium homeostasis and normal blood pressure. CORIN variants have been identified in humans and other animals, but no studies of CORIN polymorphisms have been conducted in northeastern China. This study aims to investigate the association of 2 single nucleotide polymorphisms (SNPs) in CORIN (rs2271037 and rs3749585) with hypertension, as well as their potential interactions with some risk factors of hypertension in a Han population of northeastern China. A case-control study, including 402 patients with hypertension and 406 participants with normal blood pressure, was conducted in Liaoning province. SNP genotyping was carried out by high resolution melting (HRM) after polymerase chain reaction amplifications. Since rs3749585 is located in 3' untranslated region (UTR) of CORIN, in silico analysis was used to predict target micro RNAs on TargetScan, miRanda, and DIANA-microT. As a result, mutant T allele in rs2271037 (odds ratio [OR], 1.693; 95% confidence [CI], 1.528-1.877; p 0.001) and C allele in rs3749585 (OR, 1.114; 95% CI 1.011-1.227; p = 0.029) increased the risk of hypertension, comparing with wild G allele and T allele, respectively. Patients with genotype TT (OR, 10.209; 95% CI, 6.414-16.250; p 0.001) and GT (OR, 1.730; 95% CI, 1.226-2.443; p = 0.002) have higher risk of hypertension than those with genotype GG. SNP rs2271037 was significantly associated with susceptibility to hypertension in all genetic models (dominant model: OR, 2.879; 95% CI, 2.080-3.986; p 0.001; recessive model: OR, 7.159; 95% CI, 4.779-10.724; p 0.001; additive model: OR, 1.535; 95% CI, 1.163-2.027; p = 0.002). SNP rs3749585 was significantly correlated with hypertension susceptibility only in dominant model (OR, 1.533; 95% CI, 1.073-2.189; p = 0.019), but not in recessive model (OR, 1.220; 95% CI, 0.906-1.644; p = 0.191) or additive model (OR, 0.915; 95% CI, 0.694-1.205; p = 0.527). After adjusting for age, gender, body mass index (BMI), smoking, low-density lipoprotein cholesterol, and serum sodium level in logistic models, the same statistical results were obtained. Interaction study showed the association between CORIN polymorphisms and hypertension could be changed by overweight (BMI 25 kg/m(2)). In silico analyses implicated hsa-miR-495 as a target miRNA that potentially interacts with the 3' UTR of CORIN. In conclusion, polymorphisms of rs2271037 and rs3749585 in CORIN were significantly associated with hypertension in a Han population of northeastern China. The mutant-type T allele of rs2271037 and C allele of rs3749585 might increase the susceptibility to hypertension in this population.