Ankle–brachial index in relation to the natriuretic peptide system polymorphisms and urinary sodium excretion in Chinese

•In a Chinese population, we studied 16 genetic variants in natriuretic peptides.•We studied ankle-brachial index (ABI) while accounting for sodium intake.•The rs6668352 variant interacted with sodium intake to be associated with ABI.•The association of rs6668352 with ABI was apparent on high sodium intake.•Plasma proBNP level was positively correlated with ABI.

ObjectiveRecent studies have demonstrated that the natriuretic pepetides induce endothelial regeneration and angiogenesis after vascular injury through the autocrine or paracrine action, and might have an inhibitory effect on atherosclerosis. We therefore systematically investigated single nucleotide polymorphisms (SNPs) in the natriuretic peptide system in relation to ankle–brachial index (ABI) in a Chinese population.MethodsThe study population was recruited from a mountainous area 500 km south of Shanghai from 2003 to 2009. Using the SNapShot method, we first genotyped 951 subjects enrolled in 2005 for 16 SNPs and then the remaining 1355 subjects as validation for 5 SNPs selected from the primary study. ABI and plasma proBNP were measured using the Omron VP-2000/1000 device and the Elecsys proBNP immunoassay, respectively.ResultsOverall, the genetic associations were not significant (P ≥ 0.07). However, in the primary study, there was significant (Pint ≤ 0.045) interaction between 3 SNPs (rs6668352, rs198388, and rs198389) at the NPPA–NPPB locus and urinary sodium excretion in relation to ABI, and the rs6668352 polymorphism had the strongest association (Pint = 0.018). In the primary combined with the validation study populations, the interaction between the rs6668352 polymorphism and urinary sodium excretion in relation to ABI remained statistically significant (Pint = 0.0036). After adjustment for covariates, the rs6668352 A allele carriers, compared with GG homozygotes, had a higher ABI (mean ± standard error, 1.103 ± 0.006 vs. 1.084 ± 0.004, P = 0.009) and lower risk of peripheral arterial disease (PAD, defined as an ABI < 0.90, odds ratio 0.37, 95% confidence interval: 0.14–0.98, P = 0.04) in the subjects of high sodium intake.ConclusionThe minor alleles of 3 SNPs at the NPPA–NPPB locus are associated with a lower risk of PAD, especially in the subjects of high sodium intake.