期刊
CIRCULATION-CARDIOVASCULAR GENETICS
卷 4, 期 4, 页码 375-U85出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCGENETICS.110.958629
关键词
blood pressure; epithelial sodium channel; genetic variant; salt sensitivity
资金
- National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD [U01HL072507, R01HL087263, R01HL090682]
Background-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). Methods and Results-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, alpha, beta, and gamma (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 x 10(-5); rs4073291, P = 1.1 x 10(-5); rs7404408, P = 1.9 x 10(-5); rs5735, P = 3.0 x 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. Conclusions-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.
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