International Journal of Medical Sciences

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18 December 2017

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Int J Med Sci 2007; 4(3):146-152. doi:10.7150/ijms.4.146

Research Paper

A Novel Variable Number of Tandem Repeat of the Natriuretic Peptide Precursor B gene's 5'-Flanking Region is Associated with Essential Hypertension among Japanese Females

Kotoko Kosuge1, Masayoshi Soma1,3, Tomohiro Nakayama2, Noriko Aoi2, Mikano Sato2, Yoichi Izumi1, Koichi Matsumoto1

1. Division of Nephrology and Endocrinology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
2. Division of Molecular Diagnostics, Advanced Medical Research Center, Nihon University School of Medicine, Tokyo, Japan
3. Division of General Medicine, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan

Abstract

Background: Brain natriuretic peptide (BNP) acts primarily as a cardiac hormone; it is produced by the ventricle and has both vasodilatory and natriuretic actions. Therefore, the BNP gene is thought to be a candidate gene for essential hypertension (EH). The present study identified variants in the 5'-flanking region of natriuretic peptide precursor B (NPPB) gene and assessed the relationship between gene variants and EH.

Methods: The polymerase chain reaction-single strand conformation polymorphism method and nucleotide sequencing were used to identify variants.

Results: A novel variable number of tandem repeat (VNTR) polymorphism in the 5'-flanking region (-1241 nucleotides from the major transcriptional initiation site) was discovered. This VNTR polymorphism is a tandem repeat of the 4-nucleotide sequence TTTC. There were 8 alleles, ranging from 9-repeat to 19-repeat. An association study was done involving 317 EH patients and 262 age-matched normotensive (NT) subjects. The 11-repeat allele was the most frequent (88.2%); the 16-repeat allele was the second most frequent (10.5%) in the NT group. The observed and expected genotypes were in agreement with the predicted Hardy-Weinberg equilibrium values (P=0.972). Among females, the overall distribution of genotypes was significantly different between the EH and NT groups (p=0.039). The frequency of the 16-repeat allele was significantly lower in the female EH group (6.5%) than in the female NT group (12.2%, p=0.046).

Conclusions: The 16-repeat allele of the VNTR in the 5'-flanking region of NPPB appears to be a useful genetic marker of EH in females.

Keywords: Brain natriuretic peptide, essential hypertension, variable number of tandem repeat, association study

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How to cite this article:
Kosuge K, Soma M, Nakayama T, Aoi N, Sato M, Izumi Y, Matsumoto K. A Novel Variable Number of Tandem Repeat of the Natriuretic Peptide Precursor B gene's 5'-Flanking Region is Associated with Essential Hypertension among Japanese Females. Int J Med Sci 2007; 4(3):146-152. doi:10.7150/ijms.4.146. Available from http://www.medsci.org/v04p0146.htm