title: Genome-wide linkage and positional association study of blood pressure response to dietary sodium intervention: the GenSalt Study.
abstract: The authors conducted a genome-wide linkage scan and positional association analysis to identify the genetic determinants of salt sensitivity of blood pressure (BP) in a large family-based, dietary-feeding study. The dietary intervention was conducted among 1,906 participants in rural China (2003-2005). A 7-day low-sodium intervention was followed by a 7-day high-sodium intervention. Salt sensitivity was defined as BP responses to low- and high-sodium interventions. Signals of the logarithm of the odds to the base 10 (LOD ≥ 3) were detected at 33-42 centimorgans of chromosome 2 (2p24.3-2p24.1), with a maximum LOD score of 3.33 for diastolic blood pressure responses to high-sodium intervention. LOD scores were 2.35-2.91 for mean arterial pressure (MAP) and 0.80-1.49 for systolic blood pressure responses in this region, respectively. Correcting for multiple tests, single nucleotide polymorphism (SNP) rs11674786 (2.7 kilobases upstream of the family with sequence similarity 84, member A, gene (FAM84A)) in the linkage region was significantly associated with diastolic blood pressure (P = 0.0007) and MAP responses (P = 0.0007), and SNP rs16983422 (2.8 kilobases upstream of the visinin-like 1 gene (VSNL1)) was marginally associated with diastolic blood pressure (P = 0.005) and MAP responses (P = 0.005). An additive interaction between SNPs rs11674786 and rs16983422 was observed, with P = 7.00 × 10(-5) and P = 7.23 × 10(-5) for diastolic blood pressure and MAP responses, respectively. The authors concluded that genetic region 2p24.3-2p24.1 might harbor functional variants for the salt sensitivity of BP.
authors.affiliation: Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, 1440 Canal Street, New Orleans, LA 70112, USA. hmei@tulane.edu
authors.forename: Hao
authors.initials: H
authors.lastname: Mei
authors.forename: Dongfeng
authors.initials: D
authors.lastname: Gu
authors.forename: James E
authors.initials: JE
authors.lastname: Hixson
authors.forename: Treva K
authors.initials: TK
authors.lastname: Rice
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Lawrence C
authors.initials: LC
authors.lastname: Shimmin
authors.forename: Karen
authors.initials: K
authors.lastname: Schwander
authors.forename: Tanika N
authors.initials: TN
authors.lastname: Kelly
authors.forename: De-Pei
authors.initials: DP
authors.lastname: Liu
authors.forename: Shufeng
authors.initials: S
authors.lastname: Chen
authors.forename: Jian-feng
authors.initials: JF
authors.lastname: Huang
authors.forename: Cashell E
authors.initials: CE
authors.lastname: Jaquish
authors.forename: Dabeeru C
authors.initials: DC
authors.lastname: Rao
authors.forename: Jiang
authors.initials: J
authors.lastname: He
mesh_terms: D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects / Q000235:genetics*; D002681:China; D004039:Diet, Sodium-Restricted; D005260:Female; D008040:Genetic Linkage / Q000235:genetics; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012982:Sodium, Dietary / Q000494:pharmacology*
chemical_list: D012982:Sodium, Dietary