Department of Medicine, University of Virginia Health System, Charlottesville, VA 22908-1414, USA.
Hypertension. 2012 Nov;60(5):1359-66. doi: 10.1161/HYPERTENSIONAHA.112.196071. Epub 2012 Sep 17.
Previous studies have demonstrated that single nucleotide polymorphisms (SNPs) of the sodium-bicarbonate co-transporter gene (SLC4A5) are associated with hypertension. We tested the hypothesis that SNPs in SLC4A5 are associated with salt sensitivity of blood pressure in 185 whites consuming an isocaloric constant diet with a randomized order of 7 days of low Na(+) (10 mmol/d) and 7 days of high Na(+) (300 mmol/d) intake. Salt sensitivity was defined as a ≥ 7-mm Hg increase in mean arterial pressure during a randomized transition between high and low Na(+) diet. A total of 35 polymorphisms in 17 candidate genes were assayed, 25 of which were tested for association. Association analyses with salt sensitivity revealed 3 variants that associated with salt sensitivity, 2 in SLC4A5 (P<0.001) and 1 in GRK4 (P=0.020). Of these, 2 SNPs in SLC4A5 (rs7571842 and rs10177833) demonstrated highly significant results and large effects sizes, using logistic regression. These 2 SNPs had P values of 1.0 × 10(-4) and 3.1 × 10(-4) with odds ratios of 0.221 and 0.221 in unadjusted regression models, respectively, with the G allele at both sites conferring protection. These SNPs remained significant after adjusting for body mass index and age (P=8.9 × 10(-5) and 2.6 × 10(-4) and odds ratios 0.210 and 0.286, respectively). Furthermore, the association of these SNPs with salt sensitivity was replicated in a second hypertensive population. Meta-analysis demonstrated significant associations of both SNPs with salt sensitivity (rs7571842 [P=1.2 × 10(-5)]; rs1017783 [P=1.1 × 10(-4)]). In conclusion, SLC4A5 variants are strongly associated with salt sensitivity of blood pressure in 2 separate white populations.
先前的研究表明，钠-碳酸氢盐共转运体基因（SLC4A5）的单核苷酸多态性（SNPs）与高血压有关。我们检验了一个假设，即 SLC4A5 中的 SNPs 与 185 名白人在摄入等热量恒定饮食时的血压盐敏感性有关，这些白人以随机顺序分别摄入 7 天低钠（10mmol/d）和 7 天高钠（300mmol/d）饮食。盐敏感性定义为在高盐和低盐饮食之间随机转换期间平均动脉压升高≥7mmHg。共检测了 17 个候选基因中的 35 个多态性，其中 25 个进行了关联分析。与盐敏感性相关的关联分析显示，3 个变体与盐敏感性相关，其中 2 个在 SLC4A5 中（P<0.001），1 个在 GRK4 中（P=0.020）。其中，SLC4A5 中的 2 个 SNPs（rs7571842 和 rs10177833）在逻辑回归中显示出非常显著的结果和较大的效应大小。这两个 SNP 的 P 值分别为 1.0×10(-4)和 3.1×10(-4)，未调整的回归模型中优势比分别为 0.221 和 0.221，两个位点的 G 等位基因均具有保护作用。在调整体重指数和年龄后，这些 SNP 仍然具有统计学意义（P=8.9×10(-5)和 2.6×10(-4)，优势比分别为 0.210 和 0.286）。此外，这两个 SNP 与盐敏感性的关联在第二个高血压人群中得到了复制。荟萃分析显示，这两个 SNP 与盐敏感性均具有显著相关性（rs7571842[P=1.2×10(-5)]；rs1017783[P=1.1×10(-4)]）。总之，SLC4A5 变体与两个独立的白人人群的血压盐敏感性密切相关。
