Bukovinian State Medical University, Chernivtsi, Ukraine.
Donauklinik, Neu Ulm, Germany.
Endocr Regul. 2024 Oct 1;58(1):195-205. doi: 10.2478/enr-2024-0023. Print 2024 Jan 1.
The aim of this study was to evaluate the association of the α-adducin-1 gene () (Gly460Trp [rs4961]) polymorphism and its expression in association with renal dysfunction and sodium sensitivity in hypertensive patients in western Ukrainian population. One-hundred patients with essential arterial hypertension (EAH) and hypertensive-mediated target organ damage (stage 2), moderate, high, and very high cardiovascular risk were enrolled in case-control study. Sixty healthy individuals were assigned as controls. Sodium sensitivity and sodium resistance were determined by salt load reaction. The (rs4961) genotyping was performed in RT-PCR. The expression of the quantitative trait loci (eQTL) of gene (rs4961) (chr4:2906707 [hg19]) was confirmed in 37 tissues and organs with 23 phenotypic traits. Two hundred eQTL associations revealed - all cis-variants (cis-QTL); 73 methylation QTL (mQTL), 34 splicing QTL (sQTL), 14 histone modification QTL (hQTL), 2 protein QTL (pQTL), 23 transcript utilization QTL (tuQTL), and 4 loci of incorporated long noncoding areas of RNA (lncRNA). GG-genotype unreliably enhances EAH risk (OR=1.92; 95%CI: 0.90-4.10; p=0.066). Sodium sensitivity was observed in 54.0% of patients and in 20.0% of controls (c2=17.89; p<0.001). Sodium sensitivity in T-allele carriers of the gene (1378G>T; rs4961) dominated 12-fold in general (OR 95%CI: 2.24-64.29; p=0.001), in women - 4.71 times (OR 95%CI: 1.92-11.56; p<0.001), and in men - 4.09 times (OR 95%CI: 1.03-16.28; p=0.041). Sodium sensitivity elevated the likelihood of severe EAH twice (OR=2.19; OR 95%CI: 1.00-5.05; p=0.049). T-allele associates with sodium sensitivity in essential arterial hypertension patients and increases the risk of hypertension regardless the gender. Sodium sensitivity enhances the probability of severe essential arterial hypertension in observed population.
这项研究的目的是评估 α-内收蛋白-1 基因（）（甘氨酸 460 脯氨酸[rs4961]）多态性与肾功能障碍和钠敏感性的关联，以及其在乌克兰西部高血压患者中的表达。在这项病例对照研究中，纳入了 100 名患有原发性高血压（EH）和高血压介导的靶器官损伤（2 期）、中度、高和极高心血管风险的患者。60 名健康个体被指定为对照组。通过盐负荷反应确定钠敏感性和钠抵抗。使用 RT-PCR 进行（rs4961）基因分型。在 37 种组织和器官中，对 基因（rs4961）（chr4：2906707[hg19]）的数量性状基因座（eQTL）的表达进行了确认，具有 23 种表型特征。发现了 200 个 eQTL 关联-所有顺式变异（cis-QTL）；73 个甲基化 QTL（mQTL），34 个剪接 QTL（sQTL），14 个组蛋白修饰 QTL（hQTL），2 个蛋白质 QTL（pQTL），23 个转录物利用 QTL（tuQTL）和 4 个整合长非编码 RNA 区域的位点（lncRNA）。GG 基因型不可靠地增加 EAH 风险（OR=1.92；95%CI：0.90-4.10；p=0.066）。54.0%的患者和 20.0%的对照组存在钠敏感性（c2=17.89；p<0.001）。在基因（1378G>T；rs4961）T 等位基因携带者中，钠敏感性普遍增加 12 倍（OR 95%CI：2.24-64.29；p=0.001），女性增加 4.71 倍（OR 95%CI：1.92-11.56；p<0.001），男性增加 4.09 倍（OR 95%CI：1.03-16.28；p=0.041）。钠敏感性使严重 EAH 的可能性增加了两倍（OR=2.19；OR 95%CI：1.00-5.05；p=0.049）。T 等位基因与原发性高血压患者的钠敏感性有关，并增加了高血压的风险，无论性别如何。在观察人群中，钠敏感性增加了严重原发性高血压的可能性。
