Abstract 3272: B-Type Natriuretic Peptide Single Nucleotide Polymorphism rs198389 Impacts Test Characteristics of Common Assays
Background: Assays for the cardiac hormone B-type natriuretic peptide (BNP) are widely used in the diagnosis and prognosis of left ventricular (LV) dysfunction and heart failure. The functional single nucleotide polymorphism rs198389 in the promoter region of the BNP gene has been associated with higher BNP levels. We hypothesized that rs198389 would impact the test characteristics of two commonly used BNP assays to detect a left ventricular (LV) ejection fraction ≤40% and ≤50% in the general community.
Methods: We genotyped a random sample of the general population ≥45 years; n=1970) from Olmsted County, MN, for rs198389. BNP plasma levels (Biosite BNP and Roche NTproBNP assays) as well as biochemical, clinical, and echocardiographic parameters were determined.
Results: Genotype frequencies were in Hardy-Weinberg equilibrium (p=0.98): TT 32.7%, TC 49.9%, and CC 17.3%. Genotypes did not differ with regard to presence or history of cardiovascular disease. The C-allele independently predicted higher BNP in multivariate analysis (p<0.0001 for both assays). When using previously reported genotype-unadjusted cutpoints for the detection of LV ejection fraction ≤40%, sensitivity increased with the number of C-alleles (for TT, TC, CC, respectively: Biosite: 77, 86, 83%; NTproBNP: 71, 100, 83%). In contrast, specificity decreased (Biosite: 86, 82, 76%; NTproBNP: 89, 86, 81%). If a positive test result would be followed up with an imaging study, this would be required more often with C-alleles (Biosite: 16, 19, 25%; NTproBNP: 13, 15, 20%) with more studies being negative. In contrast, the number of subjects with missed LV dysfunction would be smaller with C-alleles (Biosite: 24, 14, 17%; NTproBNP: 29, 0, 17%). Qualitatively similar findings were obtained in male and female subgroups and when the assays were assessed for the detection of an LV ejection fraction ≤50%.
Conclusions: The C-allele of rs198389 is associated with higher plasma BNP and confounds the test characteristics of commonly used assays to detect reduced LV ejection fraction in the general population. Therefore, it may be worthwhile to define genotype-specific reference ranges and to test whether addition of genotype to BNP assays can improve screening for LV dysfunction in the community.