Genetic polymorphism of the type A human natriuretic peptide receptor (NPR-A) gene contributes to the interindividual variability in the BNP system

Aims: To analyse the contribution of recently described genetic polymorphisms in the human natriuretic peptide receptor (NPR-A) to the interindividual variability in the BNP system. Methods and results: We evaluated NT-proBNP in 402 subjects, including healthy controls (n = 93), patients with acute coronary syndrome (n = 194) and heart failure (n = 115). Three polymorphic sites encoding six common haplotypes of the NPR-A receptor gene, including three haplotypes in the 5' region (CT11, CT10 and CT6) and three haplotypes in the 3' region (3-plus, 4-minus and 4-plus), were studied. The frequency of the identified 4-nimus haplotype was higher in control subjects with high NT-proBNP (>75th percentile) levels as compared to those with low NT-proBNP levels (15.2% vs. 5.7%,p<0.05). In the control subjects, carriers of the 4-plus/4-minus genotype had about 2-fold higher median NT-proBNP levels than individuals with other genetic variants (142 pg/ml (88-371 pg/ml) vs. 71 pg/ml (35-111 pg/ml, p=0.011). In contrast, in patients with cardiovascular disorders no relation between NT-proBNP and the described polymorphisms was observed. Conclusion: The 4-minus haplotype of the NPR-A receptor gene is associated with high NT-proBNP values and is a genetic determinant of the interindividual variability in the BNP system in healthy individuals but probably not in patients with cardiovascular disorders. (C) 2008 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.