Haplotype-based case-control study of the association between the guanylate cyclase activator 2B (GUCA2B, Uroguanylin) gene and essential hypertension.
Uroguanylin (gene name: guanylate cyclase activator 2B, GUCA2B) is a peptide regulator of intestinal salt and water transport. It has been reported that the uroguanylin knockout mouse exhibits elevated blood pressure. Therefore, the GUCA2B gene is thought to be a susceptibility gene for essential hypertension (EH). Despite extensive studies, however, the relationship between the GUCA2B gene and EH has not yet been defined. The aim of this study was to assess the association between the human GUCA2B gene and EH. Using four single nucleotide polymorphisms (SNPs), we conducted a genetic association study in 281 EH patients and 279 age-matched normotensive (NT1) individuals. To derive more reliable data, we performed a duplicate case-control study in which we recruited another normotensive group (NT2). There was no significant difference in the overall distribution of alleles for any of the SNPs between the EH and NT1 groups, or between the EH and NT2 groups. Therefore, these four SNPs cannot be the genetic markers for EH. The occurrences of the C-A haplotype (rs883062-rs1047047) and the C-A-G haplotype (rs883062-rs1047047-rs2297566) were significantly higher in the EH group than in the NT1 group (p<0.0001) or the NT2 group (p<0.0001). These results suggest that the C-A haplotype and the C-A-G haplotype of the GUCA2B gene are the genetic markers for EH, and that GUCA2B or a neighboring gene might be a susceptibility gene for EH.
Division of Molecular Diagnostics, Department of Advanced Medical Science, Nihon University School of Medicine, Tokyo, Japan.
Yukie
Y
Yoshikawa
Tomohiro
T
Nakayama
Kosuke
K
Saito
Peng
P
Hui
Akihiko
A
Morita
Naoyuki
N
Sato
Teruyuki
T
Takahashi
Masaaki
M
Tamura
Ichiro
I
Sato
Noriko
N
Aoi
Nobutaka
N
Doba
Shigeaki
S
Hinohara
Masayoshi
M
Soma
Ron
R
Usami
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005260:Female; D006239:Haplotypes; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D045265:Natriuretic Peptides / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
D045265:Natriuretic Peptides; C084362:uroguanylin