健康診断受診者および虚血性脳血管障害患者
における ANP 遺伝子多型の比較と血中 ANP 濃度

太　田　敦　美*1　園　田　　　啓*2　谷田部　陽　子*3　竹　下　栄　子*4
齊　藤　郁　夫*5　伊　東　大　介*6　棚　橋　紀　夫*7　福　内　靖　男*8
菊　池　春　人*9　村　田　　　満*10 渡　辺　清　明*11　　　　　　　　　　　
　　　　　　　　　　　　　　　　　　　　　　
Study of Genotype Frequencies of ANP ⁶⁶⁴G/A Polymorphism in Normal Subjects
and CVD Patients, and its Association with Plasma ANP Levels

Atsumi OHTA*1, Akira SONODA*2, Yoko YATABE*3, Eiko TAKESHITA*4,
Ikuo SAITO, MD*5, Daisuke ITO, MD*6, Norio TANAHASHI, MD*7,
Yasuo FUKUUCHI, MD*8, Haruhito KIKUCHI, MD*9,
Mitsuru MURATA, MD*10 and Kiyoaki WATANABE, MD*11

Atrial natriuretic peptide(ANP) plays a crucial role in regulating body fluid volume and blood pressure, by promoting natriuresis and vasodilatation and by inhibiting the renin-angiotensin system. Plasma levels of ANP are elevated in heart failure and hypertension, and ANP is thus believed to be involved in the pathogenesis of cardiovascular disorders. Previous case-control studies have shown that a single nucleotide polymorphism in the first exon of ANP gene, ⁶⁶⁴G/A, is associated with a risk of cerebrovascular disease(CVD) in white populations. Plasma ANP levels, however, were not evaluated in these studies in relation to the ⁶⁶⁴G/A, although the nucleotide substitution causes an amino-acid change in the propeptide of ANP. In this study, we analyzed the genotype frequencies of the ⁶⁶⁴G/A in Japanese patients with CVD (n＝199) and age- and gender-matched control subjects(n＝176). Genotypes with the ⁶⁶⁴A allele in the Japanese control subjects(G/A and A/A 12.5%) were apparently more frequent compared to the published frequency of the white control population(G/A and A/A 6.6%, p＝0.0437). Genotypes with the ⁶⁶⁴A allele, however, were not significantly different between our CVD patients(15.1%) and controls(12.5% p＝0.4714). In the control group(n＝137), the mean plasma ANP levels were not different between the ⁶⁶⁴G/G(15.7±10.7pg/ml) and ⁶⁶⁴G/A genotypes(15.6±6.8pg/ml, p＝0.9708). These results suggest that there is a racial difference in the allele frequency of ⁶⁶⁴G/A, and that this polymorphism may not be a major risk factor for CVD in the Japanese, nor is it a major determinant of plasma ANP level.
[Rinsho Byori 50 : 296〜300, 2002]

*1Department of Laboratory Medicine, School of Medicine, Keio University, Shinjuku-ku, Tokyo 161-8582

【Key Words】atrial natriuretic peptide(心房性ナトリウム利尿ペプチド)，cerebrovascular disease(脳血管障害)，genetic polymorphism(遺伝子多型)

受付2001年8月1日・受理2001年12月13日
*1〜4,9〜11慶應義塾大学医学部中央臨床検査部，*5同　保健管理センター，
*6〜8,10同　内科(〒160-8582 東京都新宿区信濃町35)

E-mail :atsumiohta@aol.com