Beijing Municipal Key Laboratory of Clinical Epidemiology, Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, Beijing 100054, China.
Nutrients. 2022 Sep 26;14(19):3990. doi: 10.3390/nu14193990.
Long noncoding RNA (lncRNA) plays an important role in cardiovascular diseases, but the involvement of lncRNA in salt sensitivity of blood pressure (SSBP) is not well-known. We aimed to explore the association of sixteen single-nucleotide polymorphisms (SNPs) in five lncRNA genes (KCNQOT1, lnc-AGAP1-8:1, lnc-IGSF3-1:1, etc.) with their expression and susceptibility to SSBP. A two-stage association study was conducted among 2057 individuals. Quantified expression of the lncRNA was detected using real-time PCR. Genotyping was accomplished using the MassARRAY System. The expression quantitative tra2it loci test and the generalized linear model were utilized to explore the function of SNPs. One-sample Mendelian randomization was used to study the causal relationship between KCNQOT1 and SSBP. Significant effects were observed in KCNQ1OT1 expressions on the SSBP phenotype (p < 0.05). Rs10832417 and rs3782064 in KCNQ1OT1 may influence the secondary structure, miRNA binding, and expression of KCNQ1OT1. Rs10832417 and rs3782064 in KCNQ1OT1 were identified to be associated with one SSBP phenotype after multiple testing corrections and may be mediated by KCNQ1OT1. One-sample Mendelian randomization analyses showed a causal association between KCNQ1OT1 and SSBP. Our findings suggest that rs10832417 and rs3782064 might be associated with a lower risk of SSBP through influencing the KCNQ1OT1 secondary structure and miRNA binding, resulting in changes in KCNQ1OT1 expression.
长链非编码 RNA（lncRNA）在心血管疾病中发挥着重要作用，但 lncRNA 与血压盐敏感性（SSBP）的关系尚不清楚。我们旨在探讨五个 lncRNA 基因（KCNQOT1、lnc-AGAP1-8:1、lnc-IGSF3-1:1 等）中的 16 个单核苷酸多态性（SNP）与它们的表达及 SSBP 易感性之间的关系。对 2057 名个体进行了两阶段关联研究。使用实时 PCR 检测 lncRNA 的定量表达。使用 MassARRAY 系统完成基因分型。利用表达数量性状基因座测试和广义线性模型来探讨 SNP 的功能。采用单样本 Mendelian 随机化研究 KCNQOT1 与 SSBP 之间的因果关系。在 SSBP 表型中观察到 KCNQ1OT1 表达的显著影响（p<0.05）。KCNQ1OT1 中的 rs10832417 和 rs3782064 可能影响 KCNQ1OT1 的二级结构、miRNA 结合和表达。在多重测试校正后，KCNQ1OT1 中的 rs10832417 和 rs3782064 被确定与一个 SSBP 表型相关，并且可能由 KCNQ1OT1 介导。单样本 Mendelian 随机化分析显示 KCNQ1OT1 与 SSBP 之间存在因果关系。我们的研究结果表明，rs10832417 和 rs3782064 可能通过影响 KCNQ1OT1 的二级结构和 miRNA 结合，导致 KCNQ1OT1 表达发生变化，从而与 SSBP 低风险相关。
