TY - JOUR
T1 - The effect of the brain-type natriuretic peptide single-nucleotide polymorphism rs198389 on test characteristics of common assays
AU - Costello-Boerrigter, Lisa C.
AU - Boerrigter, Guido
AU - Ameenuddin, Syed
AU - Mahoney, Douglas W.
AU - Slusser, Joshua P.
AU - Heublein, Denise M.
AU - Redfield, Margaret M.
AU - Rodeheffer, Richard J.
AU - Olson, Timothy M.
AU - Burnett, John C.
N1 - Funding Information:
This study was funded by grants HL07111 (G.B.), HL76611, HL36634, and HL55502 from the National Institutes of Health .
Funding Information:
Dr Burnett received a research grant from Bio-Rad Laboratories, Hercules, CA , which developed and owns the proBNP 1-108 assay.
PY - 2011/3
Y1 - 2011/3
N2 - OBJECTIVE: To assess in a US general adult population the effect of the functional single-nucleotide polymorphism rs198389 in the promoter region of the gene of brain-type natriuretic peptide (BNP) on 3 commonly used BNP assays, clinical phenotype, disease prevalence, overall survival, and diagnostic test characteristics of BNP as a biomarker. PATIENTS AND METHODS: We genotyped for rs198389 in a random sample of the general population (aged ≥45 years; n=1970; enrolled between June 1, 1997, and September 30, 2000) from Olmsted County, Minnesota. Patients were characterized biochemically, clinically, echocardiographically, and regarding BNP molecular forms (2 assays for BNP and 1 assay for amino-terminal proBNP). Median follow-up was 9 years. RESULTS: Genotype frequencies were in Hardy-Weinberg equilibrium (P=.98): TT genotype, n=645 (32.7%); TC genotype, n=983 (49.9%); and CC genotype, n=342 (17.4%). The C allele independently predicted higher BNP forms (P<.001 for all assays). Genotypes did not differ with regard to clinical and echocardiographic phenotype or overall survival. When previously reported genotype-unadjusted cut points for the detection of left ventricular ejection fraction less than or equal to 40% (n=37 [1.9%]) and less than or equal to 50% (n=116 [6.0%]) were used, sensitivity generally increased with the number of C alleles, whereas specificity decreased, both on average by more than 10% for the TT vs CC genotype. CONCLUSION: The C allele of rs198389 is common in the general US population and is associated with higher concentrations of BNP molecular forms but not with cardiovascular phenotype or survival. The C allele confounds the test characteristics of commonly used assays.
AB - OBJECTIVE: To assess in a US general adult population the effect of the functional single-nucleotide polymorphism rs198389 in the promoter region of the gene of brain-type natriuretic peptide (BNP) on 3 commonly used BNP assays, clinical phenotype, disease prevalence, overall survival, and diagnostic test characteristics of BNP as a biomarker. PATIENTS AND METHODS: We genotyped for rs198389 in a random sample of the general population (aged ≥45 years; n=1970; enrolled between June 1, 1997, and September 30, 2000) from Olmsted County, Minnesota. Patients were characterized biochemically, clinically, echocardiographically, and regarding BNP molecular forms (2 assays for BNP and 1 assay for amino-terminal proBNP). Median follow-up was 9 years. RESULTS: Genotype frequencies were in Hardy-Weinberg equilibrium (P=.98): TT genotype, n=645 (32.7%); TC genotype, n=983 (49.9%); and CC genotype, n=342 (17.4%). The C allele independently predicted higher BNP forms (P<.001 for all assays). Genotypes did not differ with regard to clinical and echocardiographic phenotype or overall survival. When previously reported genotype-unadjusted cut points for the detection of left ventricular ejection fraction less than or equal to 40% (n=37 [1.9%]) and less than or equal to 50% (n=116 [6.0%]) were used, sensitivity generally increased with the number of C alleles, whereas specificity decreased, both on average by more than 10% for the TT vs CC genotype. CONCLUSION: The C allele of rs198389 is common in the general US population and is associated with higher concentrations of BNP molecular forms but not with cardiovascular phenotype or survival. The C allele confounds the test characteristics of commonly used assays.
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U2 - 10.4065/mcp.2010.0708
DO - 10.4065/mcp.2010.0708
M3 - Article
C2 - 21364112
AN - SCOPUS:79952401755
SN - 0025-6196
VL - 86
SP - 210
EP - 218
JO - Mayo Clinic proceedings
JF - Mayo Clinic proceedings
IS - 3
ER -