title: Associations Between Genetic Variants of NADPH Oxidase-Related Genes and Blood Pressure Responses to Dietary Sodium Intervention: The GenSalt Study.
abstract: BACKGROUND
  The aim of this study was to comprehensively test the associations of genetic variants of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-related genes with blood pressure (BP) responses to dietary sodium intervention in a Chinese population.
  
  
  METHODS
  We conducted a 7-day low-sodium intervention followed by a 7-day high-sodium intervention among 1,906 participants in rural China. BP measurements were obtained at baseline and each dietary intervention using a random-zero sphygmomanometer. Linear mixed-effect models were used to assess the additive associations of 63 tag single-nucleotide polymorphisms in 11 NADPH oxidase-related genes with BP responses to dietary sodium intervention. Gene-based analyses were conducted using the truncated product method. The Bonferroni method was used to adjust for multiple testing in all analyses.
  
  
  RESULTS
  Systolic BP (SBP) response to high-sodium intervention significantly decreased with the number of minor T allele of marker rs6967221 in RAC1 (P = 4.51 × 10-4). SBP responses (95% confidence interval) for genotypes CC, CT, and TT were 5.03 (4.71, 5.36), 4.20 (3.54, 4.85), and 0.56 (-1.08, 2.20) mm Hg, respectively, during the high-sodium intervention. Gene-based analyses revealed that RAC1 was significantly associated with SBP response to high-sodium intervention (P = 1.00 × 10-6) and diastolic BP response to low-sodium intervention (P = 9.80 × 10-4).
  
  
  CONCLUSIONS
  These findings suggested that genetic variants of NADPH oxidase-related genes may contribute to the variation of BP responses to sodium intervention in Chinese population. Further replication of these findings is warranted.
authors.affiliation: Department of Epidemiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Xikun
authors.initials: X
authors.lastname: Han
authors.affiliation: Department of Epidemiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Zunsong
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Los Angeles, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Epidemiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for 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, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Huang
authors.affiliation: Department of Epidemiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Fangchao
authors.initials: F
authors.lastname: Liu
authors.affiliation: School of Medicine, Washington University, St. Louis, Missouri, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Gu
authors.affiliation: Department of Epidemiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for 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: School of Public Health, University of Texas, Houston, Texas, USA.
authors.forename: James E
authors.initials: JE
authors.lastname: Hixson
authors.affiliation: Department of Epidemiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Xiangfeng
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Epidemiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Laiyuan
authors.initials: L
authors.lastname: Wang
authors.affiliation: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: De-Pei
authors.initials: DP
authors.lastname: Liu
authors.affiliation: Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Los Angeles, USA.
authors.forename: Jiang
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Epidemiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Shufeng
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Epidemiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Dongfeng
authors.initials: D
authors.lastname: Gu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics; D000328:Adult; D044466:Asian People / Q000235:genetics*; D001794:Blood Pressure / Q000235:genetics*; D002681:China; D004039:Diet, Sodium-Restricted / Q000379:methods*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000178:diet therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D000074624:NADPH Oxidase 1 / Q000235:genetics; D000074662:NADPH Oxidase 2 / Q000235:genetics; D000074663:NADPH Oxidase 4 / Q000235:genetics; D000074664:NADPH Oxidase 5 / Q000235:genetics; D019255:NADPH Oxidases / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D017673:Sodium Chloride, Dietary; D016896:Treatment Outcome; D020744:rac GTP-Binding Proteins / Q000235:genetics; D020830:rac1 GTP-Binding Protein / Q000235:genetics; D000097766:RAC2 GTP-Binding Protein
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D000074624:NADPH Oxidase 1; D000074662:NADPH Oxidase 2; D000074663:NADPH Oxidase 4; D000074664:NADPH Oxidase 5; D019255:NADPH Oxidases; D017673:Sodium Chloride, Dietary; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein; D000097766:RAC2 GTP-Binding Protein; C476420:NOXA1 protein, human; C476419:NOXO1 protein, human; C107953:RAC1 protein, human; C056558:CYBB protein, human; C402799:NOX1 protein, human; C498910:NOX4 protein, human; C431571:NOX5 protein, human; C086986:CYBA protein, human; C527764:NCF2 protein, human; C113333:NCF4 protein, human
keywords: NADPH oxidase; blood pressure; genetic association; hypertension; salt sensitivity