Polymorphisms in the B-type natriuretic peptide (BNP) gene are associated with NT-proBNP levels but not with diabetic nephropathy or mortality in type 1 diabetic patients

BACKGROUND: Circulating N-terminal pro-brain natriuretic peptide (NT-proBNP) levels are elevated in patients with diabetic nephropathy and independently predict excess cardiovascular morbidity and mortality. Therefore, we investigated the association between two polymorphisms -381T/C and 1551G/A of the BNP gene, plasma NT-proBNP levels and mortality prognosis in 380 type 1 diabetic patients with and without diabetic nephropathy.

METHODS: In a prospective observational follow-up study, 197 type 1 diabetic patients with diabetic nephropathy {121 men, age [mean (SD)] 41 +/- 9.5 years, duration of diabetes 28 +/- 8.0 years, glomerular filtration rate 67 +/- 28 ml/min/1.73 m2}, and a matched control group of 183 patients with longstanding type 1 diabetes and persistent normoalbuminuria (111 men, age 43 +/- 10.0 years, duration of diabetes 27 +/- 8.3 years) were followed for 12.6 (0.0-12.9) years. Plasma NT-proBNP concentration was determined by immunoassay at baseline. The BNP genotypes were determined by TaqMan chemistry based assays.

RESULTS: The two polymorphisms were in almost complete linkage disequilibrium (r2 = 0.883) and thus only the results of the -381T/C promoter polymorphism are shown. There was no significant difference between cases and controls in either genotype distributions (cases TT 32%, TC 53%, CC 15%; controls TT 28%, TC 52%, CC 20%) or allele frequencies (cases T/C 0.58/0.42; controls T/C 0.54/0.46) for the -381T/C polymorphism. Among the 164 normoalbuminuric patients without antihypertensive treatment and previous major cardiovascular disease (CVD), the -381T/C polymorphism was associated with circulating levels of NT-proBNP [median (interquartile range) 21 (5-32), 34 (12-67) and 32 (12-58) ng/l for TT, TC and CC, respectively (P = 0.041)] persisting after adjustment for covariates (P = 0.018). During follow-up, the -381T/C polymorphism did not predict all-cause or cardiovascular mortality among type 1 diabetic patients with or without diabetic nephropathy.

CONCLUSIONS: The BNP -381T/C and 1551G/A polymorphisms are associated with circulating levels of NT-proBNP but not with prevalent overt diabetic nephropathy. These polymorphisms do not predict all-cause or cardiovascular mortality in Caucasian type 1 diabetic patients with or without diabetic nephropathy.