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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.

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Fig. 1: Effect size (β) and 95% CI for association between miRNA-related SNPs and blood pressure changes in acute salt load process.
Fig. 2: Effect size (β) and 95% CI for association between miRNA-related SNPs and blood pressure changes during diuresis shrinkage process.

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Acknowledgements

The English language usage in this paper was corrected and certified by https://www.aje.cn/services/editing/. The authors are grateful to the patients for participating in this study.

Funding

This research was funded by the National Key Research and Development Program of China (grant number No.2016YFC0900600/2016YFC0900603), the Natural Science Foundation of China (grant number 81973121, 81373076), and the Beijing Natural Science Foundation (grant number 7172023).

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Correspondence to Ling Zhang.

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Xie, Y., Liu, Z., Liu, K. et al. Polymorphisms of microRNAs are associated with salt sensitivity in a Han Chinese population: the EpiSS study. J Hum Hypertens 36, 171–183 (2022). https://doi.org/10.1038/s41371-021-00485-9

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