title: A gene-based analysis of variants in the serum/glucocorticoid regulated kinase (SGK) genes with blood pressure responses to sodium intake: the GenSalt Study.
abstract: BACKGROUND
  Serum and glucocorticoid regulated kinase (SGK) plays a critical role in the regulation of renal sodium transport. We examined the association between SGK genes and salt sensitivity of blood pressure (BP) using single-marker and gene-based association analysis.
  
  
  METHODS
  A 7-day low-sodium (51.3 mmol sodium/day) followed by a 7-day high-sodium intervention (307.8 mmol sodium/day) was conducted among 1,906 Chinese participants. BP measurements were obtained at baseline and each intervention using a random-zero sphygmomanometer. Additive associations between each SNP and salt-sensitivity phenotypes were assessed using a mixed linear regression model to account for family dependencies. Gene-based analyses were conducted using the truncated p-value method. The Bonferroni-method was used to adjust for multiple testing in all analyses.
  
  
  RESULTS
  In single-marker association analyses, SGK1 marker rs2758151 was significantly associated with diastolic BP (DBP) response to high-sodium intervention (P = 0.0010). DBP responses (95% confidence interval) to high-sodium intervention for genotypes C/C, C/T, and T/T were 2.04 (1.57 to 2.52), 1.79 (1.42 to 2.16), and 0.85 (0.30 to 1.41) mmHg, respectively. Similar trends were observed for SBP and MAP responses although not significant (P = 0.15 and 0.0026, respectively). In addition, gene-based analyses demonstrated significant associations between SGK1 and SBP, DBP and MAP responses to high sodium intervention (P = 0.0002, 0.0076, and 0.00001, respectively). Neither SGK2 nor SGK3 were associated with the salt-sensitivity phenotypes in single-maker or gene-based analyses.
  
  
  CONCLUSIONS
  The current study identified association of the SGK1 gene and BP salt-sensitivity in the Han Chinese population. Further studies are warranted to identify causal SGK1 gene variants.
authors.affiliation: Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, United States of America.
authors.forename: Changwei
authors.initials: C
authors.lastname: Li
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: Xueli
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, United States of America; Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana, United States of America.
authors.forename: Jiang
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Epidemiology, Human Genetics and Environmental Sciences, University of Texas School of Public Health, Houston, Texas, United States of America.
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: Dongfeng
authors.initials: D
authors.lastname: Gu
authors.affiliation: Division of Biostatistics, Washington University School of Medicine, St. Louis, Missouri, United States of America.
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, United States of America.
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: Jianfeng
authors.initials: J
authors.lastname: Huang
authors.affiliation: Division of Biostatistics, Washington University School of Medicine, St. Louis, Missouri, United States of America.
authors.forename: Charles C
authors.initials: CC
authors.lastname: Gu
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: 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: Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, United States of America.
authors.forename: Tanika N
authors.initials: TN
authors.lastname: Kelly
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D001794:Blood Pressure / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies / Q000379:methods; D005838:Genotype; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012982:Sodium, Dietary / Q000378:metabolism*; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D017874:Immediate-Early Proteins; D017346:Protein Serine-Threonine Kinases; D012982:Sodium, Dietary; D000099184:Serum-Glucocorticoid Regulated Kinases