Study of genotype frequencies of ANP 664G/A polymorphism in normal subjects and CVD patients, and its association with plasma ANP levels

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 +/- 10.7 pg/ml) and 664G/A genotypes (15.6 +/- 6.8 pg/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.