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miRNAs 多态性与汉族人群盐敏感性的关系:EpiSS 研究。

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

机构信息

Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University and Beijing Municipal Key Laboratory of Clinical Epidemiology, Beijing, China.

出版信息

J Hum Hypertens. 2022 Feb;36(2):171-183. doi: 10.1038/s41371-021-00485-9. Epub 2021 Mar 31.

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.

摘要

大多数盐敏感性 (SS) 的单核苷酸多态性 (SNP) 关联研究都集中在蛋白质编码基因中的 SNPs 上,而不是非编码 RNA 中的 SNPs。本研究试图在汉族人群中鉴定全血 microRNA (miRNA)-相关 SNPs 与 SS 风险之间的关联。对 762 例个体进行了病例对照研究。采用改良的 Sullivan 急性口服盐水负荷和利尿收缩试验来评估 SS。所有 SNPs 均通过 RT-PCR 在 Sequenom Mass ARRAY 平台 (Sequenom, San Diego, CA, USA) 上进行分析。采用遗传风险评分 (GRS) 评估联合遗传效应。总共对 24 个 miRNA 相关 SNP 进行了基因分型,其中 4 个 SNP(miR-1307-5p/rs11191676、miR-1307-5p/rs2292807、miR-145/rs41291957 和 miR-4638-3p/rs6601178)与 SS 和血压盐敏感性 (SSBP) 均相关(p≤0.05)。miR-382-5p/rs4906032 和 miR-15b-5/rs10936201 与 SSBP 相关。加权 GRS 显示,第二、三、四分位数组参与者 SS 的风险分别增加 1.760 倍(95%CI:1.068-2.903)、2.450 倍(95%CI:1.470-4.083)和 2.774 倍(95%CI:1.680-4.582)。生物信息学分析表明,这四个 SNP 风险等位基因可能影响转录因子结合并影响启动子活性。共发现 6 个与 SS 或 SSBP 相关的 miRNA 相关 SNP,多个风险等位基因的存在导致风险水平增加。

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