NDT Advance Access originally published online on June 13, 2007
Nephrology Dialysis Transplantation 2007 22(11):3235-3239; doi:10.1093/ndt/gfm360
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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
1520, Steno Diabetes Center, Gentofte, Denmark, 2Faculty of Health Science, University of Aarhus, Aarhus, Denmark and 3Department of Medical Endocrinology, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark
Correspondence and offprint requests to: Maria Lajer, Steno Diabetes Center, Niels Steensens Vej 2, DK-2820 Gentofte, Denmark. Email: mlaj{at}steno.dk
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Abstract |
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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.
Keywords: BNP; diabetic nephropathy; N-terminal pro-B-type natriuretic peptide; polymorphism; type 1 diabetes
Received for publication: 12. 1.07
Accepted in revised form: 11. 5.07
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