Polymorphisms of microRNAs are associated with salt sensitivity in a Han Chinese population: the EpiSS study.

Abstract

The majority of single-nucleotide polymorphism (SNP) association studies of salt sensitivity (SS) have focused on SNPs in protein-coding genes rather than on SNPs in noncoding RNAs. This study attempted to identify the association between whole blood microRNA (miRNA)-related SNPs and the risk of SS in a Han Chinese population. A case-control study of 762 individuals was performed. A modified Sullivan's acute oral saline load and diuresis shrinkage test was used to assess SS. All SNPs were analysed by RT-PCR on a Sequenom Mass ARRAY Platform (Sequenom, San Diego, CA, USA). A genetic risk score (GRS) was used to evaluate the joint genetic effect. In total, 24 miRNA-related SNPs were genotyped, four of which (miR-1307-5p/rs11191676, miR-1307-5p/rs2292807, miR-145/rs41291957 and miR-4638-3p/rs6601178) were associated with both SS and salt sensitivity of blood pressure (SSBP) (p ≤ 0.05). MiR-382-5p/rs4906032 and miR-15b-5/rs10936201 were associated with SSBP. Weighted GRS showed that participants in the second, third and fourth quartiles had 1.760-fold (95% CI: 1.068-2.903), 2.450-fold (95% CI: 1.470-4.083) and 2.774-fold (95% CI: 1.680-4.582) increased risk of SS, respectively. Bioinformatics analysis indicated that these four SNP risk alleles may affect transcription factor binding and influence promoter activity. A total of six miRNA-related SNPs were found to be associated with SS or SSBP, and the presence of multiple risk alleles resulted in increased risk level.