title: The role of the kallikrein-kinin system genes in the salt sensitivity of blood pressure: the GenSalt Study.
abstract: The current study comprehensively examined the association between common genetic variants of the kallikrein-kinin system (KKS) and blood pressure salt sensitivity. A 7-day low-sodium followed by a 7-day high-sodium dietary intervention was conducted among 1,906 Han Chinese participants recruited from 2003 to 2005. Blood pressure was measured by using a random-zero sphygmomanometer through the study. A total of 205 single nucleotide polymorphisms (SNPs) covering 11 genes of the KKS were selected for the analyses. Genetic variants of the bradykinin receptor B2 gene (BDKRB2) and the endothelin converting enzyme 1 gene (ECE1) showed significant associations with the salt-sensitivity phenotypes even after adjustment for multiple testing. Compared with the major G allele, the BDKRB2 rs11847625 minor C allele was significantly associated with increased systolic blood pressure responses to low-sodium intervention (P = 0.0001). Furthermore, a haplotype containing allele C was associated with an increased systolic blood pressure response to high-sodium intervention (P = 0.0009). Seven highly correlated ECE1 SNPs were shown to increase the diastolic blood pressure response to low-sodium intervention (P values ranged from 0.0003 to 0.002), with 2 haplotypes containing these 7 SNPs also associated with this same phenotype (P values ranged from 0.0004 to 0.002). In summary, genetic variants of the genes involved in the regulation of KKS may contribute to the salt sensitivity of blood pressure.
authors.affiliation: Department of Evidence Based Medicine, Fuwai Hospital and National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Beilishi Road, Beijing 100037, China. gudf@yahoo.com
authors.forename: Dongfeng
authors.initials: D
authors.lastname: Gu
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhao
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: Jie
authors.initials: J
authors.lastname: Cao
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Jianxin
authors.initials: J
authors.lastname: Li
authors.forename: Jichun
authors.initials: J
authors.lastname: Chen
authors.forename: Xu
authors.initials: X
authors.lastname: Ji
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Hu
authors.forename: Xushan
authors.initials: X
authors.lastname: Wang
authors.forename: De-Pei
authors.initials: DP
authors.lastname: Liu
authors.forename: Jiang
authors.initials: J
authors.lastname: He
mesh_terms: D000328:Adult; D000483:Alleles; D016282:Aspartic Acid Endopeptidases / Q000235:genetics; D001794:Blood Pressure / Q000187:drug effects / Q000235:genetics*; D002681:China; D004039:Diet, Sodium-Restricted; D000072396:Endothelin-Converting Enzymes; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D016234:Kallikrein-Kinin System / Q000187:drug effects / Q000235:genetics*; D008297:Male; D008666:Metalloendopeptidases / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D043782:Receptor, Bradykinin B2 / Q000235:genetics; D012982:Sodium, Dietary / Q000494:pharmacology*
chemical_list: D043782:Receptor, Bradykinin B2; D012982:Sodium, Dietary; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; C000606923:ECE1 protein, human; D000072396:Endothelin-Converting Enzymes