title: Genome-wide linkage and positional candidate gene study of blood pressure response to dietary potassium intervention: the genetic epidemiology network of salt sensitivity study.
abstract: BACKGROUND
  Genetic determinants of blood pressure (BP) response to potassium, or potassium sensitivity, are largely unknown. We conducted a genome-wide linkage scan and positional candidate gene analysis to identify genetic determinants of potassium sensitivity.
  
  
  RESULTS
  A total of 1906 Han Chinese participants took part in a 7-day high-sodium diet followed by a 7-day high-sodium plus potassium dietary intervention. BP measurements were obtained at baseline and after each intervention using a random-zero sphygmomanometer. Significant linkage signals (logarithm of odds [LOD] score, >3) for BP responses to potassium were detected at chromosomal regions 3q24-q26.1, 3q28, and 11q22.3-q24.3. Maximum multipoint LOD scores of 3.09 at 3q25.2 and 3.41 at 11q23.3 were observed for absolute diastolic BP (DBP) and mean arterial pressure (MAP) responses, respectively. Linkage peaks of 3.56 at 3q25.1 and 3.01 at 11q23.3 for percent DBP response and 3.22 at 3q25.2, 3.01 at 3q28, and 4.48 at 11q23.3 for percent MAP response also were identified. Angiotensin II receptor, type 1 (AGTR1), single-nucleotide polymorphism rs16860760 in the 3q24-q26.1 region was significantly associated with absolute and percent systolic BP responses to potassium (P=0.0008 and P=0.0006, respectively). Absolute (95% CI) systolic BP responses for genotypes C/C, C/T, and T/T were -3.71 (-4.02 to -3.40), -2.62 (-3.38 to -1.85), and 1.03 (-3.73 to 5.79) mm Hg, respectively, and percent responses (95% CI) were -3.07 (-3.33 to -2.80), -2.07 (-2.74 to -1.41), and 0.90 (-3.20 to 4.99), respectively. Similar trends were observed for DBP and MAP responses.
  
  
  CONCLUSIONS
  Genetic regions on chromosomes 3 and 11 may harbor important susceptibility loci for potassium sensitivity. Furthermore, the AGTR1 gene was a significant predictor of BP responses to potassium intake.
authors.affiliation: Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA.
authors.forename: Tanika N
authors.initials: TN
authors.lastname: Kelly
authors.forename: James E
authors.initials: JE
authors.lastname: Hixson
authors.forename: Dabeeru C
authors.initials: DC
authors.lastname: Rao
authors.forename: Hao
authors.initials: H
authors.lastname: Mei
authors.forename: Treva K
authors.initials: TK
authors.lastname: Rice
authors.forename: Cashell E
authors.initials: CE
authors.lastname: Jaquish
authors.forename: Lawrence C
authors.initials: LC
authors.lastname: Shimmin
authors.forename: Karen
authors.initials: K
authors.lastname: Schwander
authors.forename: Chung-Shuian
authors.initials: CS
authors.lastname: Chen
authors.forename: Depei
authors.initials: D
authors.lastname: Liu
authors.forename: Jichun
authors.initials: J
authors.lastname: Chen
authors.forename: Concetta
authors.initials: C
authors.lastname: Bormans
authors.forename: Pramila
authors.initials: P
authors.lastname: Shukla
authors.forename: Naveed
authors.initials: N
authors.lastname: Farhana
authors.forename: Colin
authors.initials: C
authors.lastname: Stuart
authors.forename: Paul K
authors.initials: PK
authors.lastname: Whelton
authors.forename: Jiang
authors.initials: J
authors.lastname: He
authors.forename: Dongfeng
authors.initials: D
authors.lastname: Gu
mesh_terms: D000293:Adolescent; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects* / Q000235:genetics*; D002681:China / Q000453:epidemiology; D002880:Chromosomes, Human, Pair 11; D002893:Chromosomes, Human, Pair 3; D008040:Genetic Linkage; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008126:Lod Score; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D017419:Potassium, Dietary / Q000494:pharmacology*; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics; D012982:Sodium, Dietary / Q000494:pharmacology; D055815:Young Adult
chemical_list: C544065:AGTR1 protein, human; D017419:Potassium, Dietary; D044140:Receptor, Angiotensin, Type 1; D012982:Sodium, Dietary