Genetic susceptibility to salt-sensitive hypertension in a Han Chinese population: a validation study of candidate genes.

Abstract

Salt-sensitive hypertension is a complex disease associated with genetic factors. This study aimed to identify the association between 29 candidate single-nucleotide polymorphisms and salt-sensitive hypertension in a Han Chinese population. Sixty-three participants with salt-sensitive hypertension and 279 controls with salt-resistant hypertension were recruited. A modified Sullivan's acute oral saline load and diuresis shrinkage test was used to detect blood pressure salt sensitivity. Lifestyle risk factors were obtained via a questionnaire. We used the Sequenom Mass ARRAY Platform to genotype the 29 candidate single-nucleotide polymorphisms, and the cumulative genetic risk score was used to evaluate the joint genetic effect. The frequencies of eight genotypes and five alleles in CYP11B2, PRKG1, ADRB2, FGF5, SLC8A1 and BCAT1 genes differed significantly between the salt-sensitive and salt-resistant hypertension groups. Multiple logistic regression adjusted for age and sex showed that subjects carrying rs7897633-A (PRKG1), rs434082-A (SLC8A1) and rs1042714-G (ADRB2) risk alleles had 1.83-, 2.84- and 2.40-fold increased risk for salt-sensitive hypertension, respectively. Combined risk allele analysis using the cumulative genetic risk score showed that subjects carrying one risk had 2.30-fold increased risk, and those carrying 2-4 risks had 3.32-fold increased risk for salt-sensitive hypertension. Among 29 candidate single-nucleotide polymorphisms, rs7897633-A in PRKG1, rs434082-A in SLC8A1 and rs1042714-G in ADRB2 were significantly associated with salt-sensitive hypertension. A joint effect of single-nucleotide polymorphisms from different pathways contributed to a high risk of salt-sensitive hypertension.