© 2008 European Society of Cardiology
Genetic polymorphism of the type A human natriuretic peptide receptor (NPR-A) gene contributes to the interindividual variability in the BNP system
a Kerckhoff Heart Center, Department of Cardiology Bad Nauheim, Germany
b pharmazentrum frankfurt/ZAFES, Institute for clinical pharmacology, Johann-Wolfgang-Goethe-University Frankfurt/Main, Germany
* Corresponding author. Kerckhoff Heart Center, Department of Cardiology Benekestraße 2-8, 61231 Bad Nauheim, Germany. Tel.: +49 6032 9960; fax: +49 6032 9962313. E-mail addresses: M.Weber{at}Kerckhoff-Klinik.de (M. Weber).
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Abstract |
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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-minus" 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 "-plus/4-minus" genotype had about 2-fold higher median NT-proBNP levels than individuals with other genetic variants (142pg/ml (88–371pg/ml) vs. 71pg/ml (35–111pg/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.
Key Words: Natriuretic peptide • Natriuretic peptide receptor • Acute coronary syndrome • Heart failure
Received July 29, 2007; Revised December 6, 2007; Accepted March 26, 2008
1 Both authors contributed equally.
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