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.

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

【Key Words】atrial natriuretic peptide, cerebrovascular disease, genetic polymorphism