Atrial natriuretic peptide (ANP) plays an important role in the regulation of blood pressure through sodium–water homoeostasis. Accordingly, several investigators have raised the question of whether the gene encoding ANP is involved in the aetiology of essential hypertension or related phenotypes such as salt sensitivity. Most of the studies have used anonymous polymorphic markers of the gene, and made inconclusive claims about the disease relevance of ANP. Therefore, in order to find sequence variations with potential functional significance and to characterize the pattern of linkage disequilibrium between polymorphisms, we screened a 3368-bp genomic fragment of ANP. Subsequently we tested the association of detected polymorphisms with plasma ANP levels and with hypertension status. Two new polymorphisms were identified, in the 5′-untranslated region and exon 1 respectively, as well as three previously reported polymorphisms in intron 2 and exon 3. When analysed in 102 healthy normotensive subjects, none of the polymorphisms appeared to significantly affect plasma ANP levels. A case–control study in a Japanese population (255 hypertensive and 225 normotensive individuals) revealed a marginally significant association (P = 0.026) between an ANP polymorphism located in the 5′-untranslated region (C-664G) and hypertension, but no association for the other polymorphisms. Each of the uncommon variants has an allele frequency of less than 10% in Japanese people, which may have hampered our detection of a significant association between ANP variants and hypertension status (and plasma ANP levels). The pathophysiological relevance of ANP, however, needs to be further defined in relation to hypertension-associated phenotypes, and also should be examined in different ethnic groups.
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Research Article|
February 10 2000
Genetic analysis of the atrial natriuretic peptide gene in essential hypertension
Norihiro KATO;
Norihiro KATO
*Graduate School of Human and Environmental Studies, Kyoto University, Yoshida Nihonmatsu-cho, Sakyo-ku, Kyoto, 606-8316, Japan
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Takao SUGIYAMA;
Takao SUGIYAMA
†The Institute for Adult Diseases Asahi Life Foundation, 1-9-14 Nishi-shinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan
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Hiroyuki MORITA;
Hiroyuki MORITA
‡Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
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Toru NABIKA;
Toru NABIKA
§Department of Laboratory Medicine, Shimane Medical University, Izumo 693-0021, Japan
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Hiroki KURIHARA;
Hiroki KURIHARA
‡Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
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Yukio YAMORI;
Yukio YAMORI
*Graduate School of Human and Environmental Studies, Kyoto University, Yoshida Nihonmatsu-cho, Sakyo-ku, Kyoto, 606-8316, Japan
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Yoshio YAZAKI
Yoshio YAZAKI
‡Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
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Publisher: Portland Press Ltd
Received:
July 05 1999
Revision Received:
October 01 1999
Accepted:
November 17 1999
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society and the Medical Research Society © 2000
2000
Clin Sci (Lond) (2000) 98 (3): 251–258.
Article history
Received:
July 05 1999
Revision Received:
October 01 1999
Accepted:
November 17 1999
Citation
Norihiro KATO, Takao SUGIYAMA, Hiroyuki MORITA, Toru NABIKA, Hiroki KURIHARA, Yukio YAMORI, Yoshio YAZAKI; Genetic analysis of the atrial natriuretic peptide gene in essential hypertension. Clin Sci (Lond) 1 March 2000; 98 (3): 251–258. doi: https://doi.org/10.1042/cs0980251
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