Resequencing Epithelial Sodium Channel Genes Identifies Rare Variants Associated With Blood Pressure Salt-Sensitivity: The GenSalt Study.

Autor:	Gu X; Department of Epidemiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.; Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine and School of Medicine, New Orleans, Louisiana, USA., Gu D; Department of Epidemiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China., He J; Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine and School of Medicine, New Orleans, Louisiana, USA., Rao DC; Division of Biostatistics, Washington University School of Medicine, St. Louis, Missouri, USA., Hixson JE; Department of Epidemiology, Human Genetics and Environmental Sciences, University of Texas School of Public Health, Houston, Texas, USA., Chen J; Department of Epidemiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China., Li J; Department of Epidemiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China., Huang J; Department of Epidemiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China., Wu X; Department of Epidemiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China., Rice TK; Division of Biostatistics, Washington University School of Medicine, St. Louis, Missouri, USA., Shimmin LC; Department of Epidemiology, Human Genetics and Environmental Sciences, University of Texas School of Public Health, Houston, Texas, USA., Kelly TN; Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine and School of Medicine, New Orleans, Louisiana, USA.
Jazyk:	angličtina
Zdroj:	American journal of hypertension [Am J Hypertens] 2018 Jan 12; Vol. 31 (2), pp. 205-211.
DOI:	10.1093/ajh/hpx169
Abstrakt:	Background: A resequencing study of renal epithelial sodium channel (ENaC) genes was conducted to identify rare variants associated with blood pressure (BP) salt-sensitivity. Methods: The Genetic Epidemiology Network of Salt-Sensitivity (GenSalt) study was conducted among 1,906 participants who underwent a 7-day low-sodium followed by a 7-day high-sodium feeding-study. The 300 most salt-sensitive and 300 most salt-resistant GenSalt participants were selected for the resequencing study. Three ENaC genes (SCNN1A, SCNN1B, and SCNN1G) were resequenced using capillary-based sequencing methods. Traditional burden tests were utilized to examine association between rare variants and BP salt-sensitivity. Associations of low-frequency and common variants were tested using single-marker analyses. Results: Carriers of SCNN1A rare variants had a 0.52 [95% confidence interval (CI): 0.32-0.85] decreased odds of BP salt-sensitivity compared with noncarriers. Neither SCNN1B nor SCNN1G associated with salt-sensitivity of BP in rare variant analyses (P = 0.65 and 0.48, respectively). In single-marker analyses, 3 independent common variants in SCNN1A, rs11614164, rs4764586, and rs3741914, associated with salt-sensitivity after Bonferroni correction (P = 4.4 × 10-4, 1.1 × 10-8, and 1.3 × 10-3). Each copy of the minor allele of rs4764586 was associated with a 1.36-fold (95% CI: 1.23-1.52) increased odds of salt-sensitivity, whereas each copy of the minor allele of rs11614164 and rs3741914 was associated with 0.68-fold (95% CI: 0.55-0.84) and 0.69-fold (95% CI: 0.54-0.86) decreased odds of salt-sensitivity, respectively. Conclusions: This study demonstrated for the first time a relationship between rare variants in the ENaC pathway and BP salt-sensitivity. Future replication and functional studies are needed to confirm the findings in this study. Clinical Trial Registry: Trial Number NCT00721721. (© American Journal of Hypertension, Ltd 2017. All rights reserved. For Permissions, please email: journals.permissions@oup.com)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu