title: Associations of Endothelial System Genes With Blood Pressure Changes and Hypertension Incidence: The GenSalt Study.
abstract: BACKGROUND
  We used single-marker and novel gene-based methods to examine the associations of endothelial system genes with blood pressure (BP) changes and hypertension in a longitudinal family study.
  
  
  METHODS
  The Genetic Epidemiology Network of Salt Sensitivity follow-up study was conducted among 1,768 Chinese participants from 633 families. Nine BP measurements were obtained at baseline and at 2 follow-up visits using a random-zero sphygmomanometer. Mixed-effect models were used to assess the additive associations of 206 single-nucleotide polymorphisms (SNPs) in 15 endothelial system genes with longitudinal BP changes and hypertension incidence. Gene-based analyses were conducted using the truncated product method. The Bonferroni method was used to adjust for multiple testing in all analyses.
  
  
  RESULTS
  Among those free from hypertension at baseline, 512 (32.1%) developed hypertension during the average 7.2 years of follow-up. In single-marker analyses, each copy of the minor alleles of correlated SELE markers rs4656704, rs6427212, and rs5368 were associated with increased risk of developing hypertension (P for trend = 1.48 × 10(-4), 6.69 × 10(-5), and 7.64 × 10(-5), respectively). In addition, the minor allele of SELE marker rs3917436 was associated with smaller diastolic BP (DBP) increases over time. Results of gene-based analyses confirmed associations of the SELE gene with the longitudinal BP phenotypes (P values < 1.00 × 10(-6) for DBP change and hypertension incidence). Furthermore, the DDAH1 and COL18A1 genes were associated with systolic BP change (P < 1.00 × 10(-6) and P = 4.00 × 10(-6), respectively), while EDNRA was associated with hypertension incidence (P = 2.39 × 10(-4)).
  
  
  CONCLUSIONS
  The current study provides strong evidence of a role of endothelial system genes in BP progression and hypertension incidence.
authors.affiliation: Department of Evidence Based Medicine, 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; Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, USA;
authors.forename: Fangchao
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, USA;
authors.forename: Jiang
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Evidence Based Medicine, 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: Dongfeng
authors.initials: D
authors.lastname: Gu
authors.affiliation: Division of Biostatistics, Washington University School of Medicine, St. Louis, Missouri, USA;
authors.forename: Dabeeru C
authors.initials: DC
authors.lastname: Rao
authors.affiliation: Department of Evidence Based Medicine, 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: Department of Epidemiology, Human Genetics and Environmental Sciences, University of Texas School of Public Health, Houston, Texas, USA;
authors.forename: James E
authors.initials: JE
authors.lastname: Hixson
authors.affiliation: Division of Prevention and Population Sciences, National Heart, Lung, Blood Institute, Bethesda, Maryland, USA.
authors.forename: Cashell E
authors.initials: CE
authors.lastname: Jaquish
authors.affiliation: Department of Evidence Based Medicine, 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: Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, USA;
authors.forename: Changwei
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Evidence Based Medicine, 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 Evidence Based Medicine, 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, USA;
authors.forename: Treva K
authors.initials: TK
authors.lastname: Rice
authors.affiliation: Department of Epidemiology, Human Genetics and Environmental Sciences, University of Texas School of Public Health, Houston, Texas, USA;
authors.forename: Lawrence C
authors.initials: LC
authors.lastname: Shimmin
authors.affiliation: Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, USA; tkelly@tulane.edu.
authors.forename: Tanika N
authors.initials: TN
authors.lastname: Kelly
mesh_terms: D000328:Adult; D000581:Amidohydrolases / Q000235:genetics*; D001794:Blood Pressure / Q000187:drug effects / Q000235:genetics*; D002681:China / Q000453:epidemiology; D043170:Collagen Type XVIII / Q000235:genetics*; D019040:E-Selectin / Q000235:genetics*; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006973:Hypertension / Q000453:epidemiology / Q000235:genetics; D015994:Incidence; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D044022:Receptor, Endothelin A / Q000235:genetics*; D012982:Sodium, Dietary / Q000378:metabolism
chemical_list: D043170:Collagen Type XVIII; D019040:E-Selectin; D044022:Receptor, Endothelin A; C546936:SELE protein, human; D012982:Sodium, Dietary; D000581:Amidohydrolases; C059999:dimethylargininase
keywords: blood pressure changes; common variants; endothelial; hypertension.