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 "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.
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 "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.
Authors: Shuang Liang; Richard C Brundage; Pamala A Jacobson; Anne Blaes; Mark N Kirstein Journal: Br J Clin Pharmacol Date: 2016-06-03 Impact factor: 4.335
Authors: Fabiola Del Greco M; Cristian Pattaro; Andreas Luchner; Irene Pichler; Thomas Winkler; Andrew A Hicks; Christian Fuchsberger; Andre Franke; Scott A Melville; Annette Peters; H Erich Wichmann; Stefan Schreiber; Iris M Heid; Michael Krawczak; Cosetta Minelli; Christian J Wiedermann; Peter P Pramstaller Journal: Hum Mol Genet Date: 2011-01-27 Impact factor: 6.150