title: Associations of epithelial sodium channel genes with blood pressure changes and hypertension incidence: the GenSalt study.
abstract: BACKGROUND
  We examined the associations of epithelial sodium channel (ENaC) genes with blood pressure (BP) changes and hypertension incidence in a longitudinal family study.
  
  
  METHODS
  A total of 2,755 Han Chinese participants of the Genetic Epidemiology Network of Salt Sensitivity (GenSalt) baseline examination were eligible for this study. The associations of 43 tag single nucleotide polymorphisms (SNPs) in ENaC genes with BP changes and hypertension incidence were assessed using mixed models to account for the correlations of repeated measures among individuals and within families. A genotype by time interaction term was used to model differences in longitudinal BP change according to genotype over time. Gene-based analyses were conducted using the truncated product method. The Bonferroni method was used to adjust for multiple testing in all analyses.
  
  
  RESULTS
  During an average of 7.4 years follow-up, systolic BP (SBP) and diastolic BP (DBP) increased, and approximately 33% of participants developed hypertension. SCNN1A SNP rs11064153 and SCNN1G SNP rs4401050 were significantly associated with longitudinal changes in SBP after adjustment for multiple testing (P interaction = 5.8×10(-4) and 0.001, respectively). Similar but nonsignificant trends were observed for the associations between both rs11064153 and rs4401050 and DBP changes (P interaction = 0.024 and 0.005, respectively) and between rs11604153 and hypertension incidence (P = 0.02). Gene-based analyses also supported the overall association of SCNN1G with longitudinal changes in SBP (P = 2.0×10(-4)).
  
  
  CONCLUSIONS
  Our findings indicated that SCNN1A and SCNN1G may contribute to BP changes over time in the Han Chinese population. Replication of these findings is warranted.
authors.affiliation: Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana; State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center of Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China;
authors.forename: Xueli
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana; Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana;
authors.forename: Jiang
authors.initials: J
authors.lastname: He
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center of Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; gudongfeng@vip.sina.com.
authors.forename: Dongfeng
authors.initials: D
authors.lastname: Gu
authors.affiliation: Department of Epidemiology, Human Genetics and Environmental Sciences, University of Texas School of Public Health, Houston, Texas;
authors.forename: James E
authors.initials: JE
authors.lastname: Hixson
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center of Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China;
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Huang
authors.affiliation: Division of Biostatistics, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Dabeeru C
authors.initials: DC
authors.lastname: Rao
authors.affiliation: Department of Epidemiology, Human Genetics and Environmental Sciences, University of Texas School of Public Health, Houston, Texas;
authors.forename: Lawrence C
authors.initials: LC
authors.lastname: Shimmin
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center of Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China;
authors.forename: Jichun
authors.initials: J
authors.lastname: Chen
authors.affiliation: Division of Biostatistics, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Treva K
authors.initials: TK
authors.lastname: Rice
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center of Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China;
authors.forename: Jianxin
authors.initials: J
authors.lastname: Li
authors.affiliation: Division of Biostatistics, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Karen
authors.initials: K
authors.lastname: Schwander
authors.affiliation: Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana;
authors.forename: Tanika N
authors.initials: TN
authors.lastname: Kelly
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D001794:Blood Pressure / Q000235:genetics*; D002681:China / Q000453:epidemiology; D053503:Epithelial Sodium Channels / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D006973:Hypertension / Q000175:diagnosis / Q000208:ethnology* / Q000235:genetics* / Q000503:physiopathology; D015994:Incidence; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D013997:Time Factors
chemical_list: D053503:Epithelial Sodium Channels; C507045:SCNN1A protein, human; C507052:SCNN1G protein, human
keywords: blood pressure; blood pressure changes; epithelial sodium channel (ENaC); hypertension; single nucleotide polymorphisms.
references.citation: Lancet. 2009 Nov 21;374(9703):1765-72
references.pmid: 19811816
references.citation: Circ Cardiovasc Genet. 2011 Aug 1;4(4):375-80
references.pmid: 21562341
references.citation: Curr Hypertens Rep. 2010 Feb;12(1):17-25
references.pmid: 20425154
references.citation: Kidney Blood Press Res. 2010;33(1):15-23
references.pmid: 20090362
references.citation: Annu Rev Physiol. 2002;64:877-97
references.pmid: 11826291
references.citation: J Hum Hypertens. 2007 Aug;21(8):639-46
references.pmid: 17443206
references.citation: Am J Hum Genet. 2007 Sep;81(3):559-75
references.pmid: 17701901
references.citation: J Am Soc Nephrol. 2002 Jan;13(1):80-85
references.pmid: 11752024
references.citation: Curr Hypertens Rep. 2012 Feb;14(1):46-61
references.pmid: 22161147
references.citation: J Biol Chem. 2010 Jul 30;285(31):23527-31
references.pmid: 20460373
references.citation: Drug Metab Dispos. 2001 Apr;29(4 Pt 2):553-6
references.pmid: 11259350
references.citation: J Hypertens. 2010 Jun;28(6):1210-20
references.pmid: 20486282
references.citation: Nucleic Acids Res. 2009 Jul;37(Web Server issue):W600-5
references.pmid: 19417063
references.citation: Hypertension. 2006 Mar;47(3):428-33
references.pmid: 16432044
references.citation: BMJ. 2009 May 19;338:b1665
references.pmid: 19454737
references.citation: Lancet. 2012 Dec 15;380(9859):2224-60
references.pmid: 23245609
references.citation: Chin Med J (Engl). 2012 Apr;125(8):1401-4
references.pmid: 22613642
references.citation: Lancet. 2002 Dec 14;360(9349):1903-13
references.pmid: 12493255
references.citation: BMC Genomics. 2008 Sep 22;9:431
references.pmid: 18803882
references.citation: Curr Hypertens Rep. 2003 Feb;5(1):11-8
references.pmid: 12530930
references.citation: BMC Proc. 2009 Dec 15;3 Suppl 7:S89
references.pmid: 20018085
references.citation: Nat Genet. 1995 Sep;11(1):76-82
references.pmid: 7550319
references.citation: Hypertension. 2007 Oct;50(4):672-8
references.pmid: 17698725
references.citation: Circulation. 1993 Nov;88(5 Pt 1):2460-70
references.pmid: 8222141
references.citation: Genet Epidemiol. 2002 Feb;22(2):170-85
references.pmid: 11788962
references.citation: Am J Hypertens. 2011 Sep;24(9):1035-40
references.pmid: 21654856
references.citation: Bioinformatics. 2005 Jan 15;21(2):263-5
references.pmid: 15297300
references.citation: J Hypertens. 2008 May;26(5):921-7
references.pmid: 18398334
references.citation: Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2009 Dec;31(6):740-5
references.pmid: 20078945
references.citation: Curr Hypertens Rep. 2013 Jun;15(3):134-6
references.pmid: 23536128