Zhao Qi, Gu Dongfeng, Hixson James E, Liu De-Pei, Rao Dabeeru C, Jaquish Cashell E, Kelly Tanika N, Lu Fanghong, Ma Jixiang, Mu Jianjun, Shimmin Lawrence C, Chen Jichun, Mei Hao, Hamm L Lee, He Jiang
Department of Epidemiology, Tulane University School of Medicine, New Orleans, LA, USA.
Circ Cardiovasc Genet. 2011 Aug 1;4(4):375-80. doi: 10.1161/CIRCGENETICS.110.958629. Epub 2011 May 11.
Rare mutations of the epithelial sodium channel (ENaC) lead to mendelian forms of salt-sensitive hypertension or salt-wasting hypotension. We aimed to examine the association between common variants in the ENaC genes and salt sensitivity of blood pressure (BP).
A total of 1906 Han Chinese participated in the Genetic Epidemiology Network of Salt Sensitivity (GenSalt) study, which includes a 7-day low-sodium intake (51.3 mmol sodium/d) followed by a 7-day high-sodium intake (307.8 mmol sodium/d). Nine BP measurements were obtained at baseline and each intervention period using a random-zero sphygmomanometer. Single-nucleotide polymorphisms, both tagging and functional, from the 3 ENaC subunits, α, β, and γ (SCNN1A, SCNN1B, and SCNN1G), were genotyped. Multiple common single-nucleotide polymorphisms in SCNN1G were significantly associated with BP response to low-sodium intervention (rs4073930, P=1.7×10(-5); rs4073291, P=1.1×10(-5); rs7404408, P=1.9×10(-5); rs5735, P=3.0×10(-4); rs4299163, P=0.004; and rs4499238, P=0.002) even after correcting for multiple testing. For example, under an additive model, the minor allele G of SNP rs4073291 was associated with 1.33 mm Hg lower systolic BP reduction during low-sodium intervention.
This large dietary sodium intervention study indicates that common variants of ENaC subunits may contribute to the variation of BP response to dietary sodium intake. Future studies are warranted to confirm these findings in an independent population and to identify functional variants for salt sensitivity.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00721721.
上皮钠通道（ENaC）的罕见突变会导致孟德尔形式的盐敏感性高血压或失盐性低血压。我们旨在研究ENaC基因常见变异与血压（BP）盐敏感性之间的关联。
共有1906名汉族人参与了盐敏感性遗传流行病学网络（GenSalt）研究，该研究包括7天低钠摄入期（51.3 mmol钠/天），随后是7天高钠摄入期（307.8 mmol钠/天）。在基线和每个干预期使用随机零点血压计进行9次血压测量。对3个ENaC亚基α、β和γ（SCNN1A、SCNN1B和SCNN1G）的单核苷酸多态性（包括标签单核苷酸多态性和功能性单核苷酸多态性）进行基因分型。即使在进行多重检验校正后，SCNN1G中的多个常见单核苷酸多态性仍与低钠干预后的血压反应显著相关（rs4073930，P = 1.7×10⁻⁵；rs4073291，P = 1.1×10⁻⁵；rs7404408，P = 1.9×10⁻⁵；rs5735，P = 3.0×10⁻⁴；rs4299163，P = 0.004；rs4499238，P = 0.002）。例如，在加性模型下，SNP rs4073291的次要等位基因G与低钠干预期间收缩压降低幅度低1.33 mmHg相关。
这项大型饮食钠干预研究表明，ENaC亚基的常见变异可能导致饮食钠摄入后血压反应的差异。未来有必要在独立人群中证实这些发现，并确定盐敏感性的功能性变异。
