A Novel Missense Mutation of Exon 3 in the Type A Human Natriuretic Peptide Receptor Gene: Possible Association with Essential Hypertension

Tomohiro NAKAYAMA; Masayoshi SOMA; Yoshihiro MIZUTANI; Xu XINJUAN; Junko HONYE; Yukie KANEKO; Dolkun RAHMUTULA; Noriko AOI; Kotoko KOSUGE; Satoshi SAITO; Yukio OZAWA; Katsuo KANMATSUSE; Shinichiro KOKUBUN

doi:10.1291/hypres.25.395

Clinical studies

A Novel Missense Mutation of Exon 3 in the Type A Human Natriuretic Peptide Receptor Gene: Possible Association with Essential Hypertension

Tomohiro NAKAYAMA, Masayoshi SOMA, Yoshihiro MIZUTANI, Xu XINJUAN, Junko HONYE, Yukie KANEKO, Dolkun RAHMUTULA, Noriko AOI, Kotoko KOSUGE, Satoshi SAITO, Yukio OZAWA, Katsuo KANMATSUSE, Shinichiro KOKUBUN

Author information

Tomohiro NAKAYAMA
Division of Receptor Biology, Advanced Medical Research Center
Masayoshi SOMA
Second Department of Internal Medicine, Nihon University School of Medicine
Yoshihiro MIZUTANI
Department of Ophthalmology, Nihon University School of Medicine
Xu XINJUAN
Second Department of Internal Medicine, Nihon University School of Medicine
Junko HONYE
Second Department of Internal Medicine, Nihon University School of Medicine
Yukie KANEKO
Second Department of Internal Medicine, Nihon University School of Medicine
Dolkun RAHMUTULA
Second Department of Internal Medicine, Nihon University School of Medicine
Noriko AOI
Second Department of Internal Medicine, Nihon University School of Medicine
Kotoko KOSUGE
Second Department of Internal Medicine, Nihon University School of Medicine
Satoshi SAITO
Second Department of Internal Medicine, Nihon University School of Medicine
Yukio OZAWA
Second Department of Internal Medicine, Nihon University School of Medicine
Katsuo KANMATSUSE
Second Department of Internal Medicine, Nihon University School of Medicine
Shinichiro KOKUBUN
Division of Receptor Biology, Advanced Medical Research Center

Keywords: natriuretic peptide, receptor, mutation, essential hypertension, single nucleotide polymorphism

JOURNAL FREE ACCESS

2002 Volume 25 Issue 3 Pages 395-401

DOI https://doi.org/10.1291/hypres.25.395

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Abstract

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, M341I, 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 α-helices, and that the mutation may influence receptor activities by altering the conformation of the α-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 M341I mutation in exon 3 is worth investigating for its possible association with EH. (Hypertens Res 2002; 25: 395-401)

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