A novel missense mutation of exon 3 in the type A human natriuretic peptide receptor gene: possible association with essential hypertension.
The natriuretic peptide (NP) family is involved in regulation of blood pressure and fluid volume. We recently characterized the exon/intron organization of the human type A NP receptor (hNPRA) gene. The aim of this study was to isolate the genetic markers according to the organization of this gene, and to study the association between this gene and essential hypertension. Using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis, we identified a novel missense mutation, M3411, consisting of a methionine (ATG) to isoleucine (ATC) substitution at nucleotide 1023 in exon 3. Computer-aided three-dimensional structural analysis suggested that M341 exists in the loop between two alpha-helices, and that the mutation may influence receptor activities by altering the conformation of the alpha-helices. We performed an association study of the mutation in 210 essential hypertension (EH) patients and 210 normotensive controls. The overall distribution of alleles was not significantly different between the control and EH groups. However, the C/C homozygous genotype was found only in the EH group. The ratio of plasma brain natriuretic peptide (BNP)/mean blood pressure of the C/C genotype was significantly higher than that of the G/G genotype or the G/C genotype. We conclude that the significance of homozygous M3411 mutation in exon 3 is worth investigating for its possible association with EH.
Nakayama
Tomohiro
T
Division of Receptor Biology, Advanced Medical Research Center, Tokyo, Japan. tnakayam@med.nihon-u.ac.jp
Soma
Masayoshi
M
Mizutani
Yoshihiro
Y
Xinjuan
Xu
X
Honye
Junko
J
Kaneko
Yukie
Y
Rahmutula
Dolkun
D
Aoi
Noriko
N
Kosuge
Kotoko
K
Saito
Satoshi
S
Ozawa
Yukio
Y
Kanmatsuse
Katsuo
K
Kokubun
Shinichiro
S
D000328:Adult; D000368:Aged; D009320:Atrial Natriuretic Factor / Q000097:blood; D019281:Dimerization; D005091:Exons / Q000235:genetics*; D005838:Genotype; D006162:Guanylate Cyclase / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics*; D020097:Natriuretic Peptide, Brain / Q000097:blood; D017461:Receptors, Atrial Natriuretic Factor / Q000737:chemistry / Q000235:genetics*
D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor; D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor; C091715:atrial natriuretic factor receptor A