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.
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 diabeticpatients with and without diabetic nephropathy. METHODS: In a prospective observational follow-up study, 197 type 1 diabeticpatients 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 diabeticpatients 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 diabeticpatients with or without diabetic nephropathy.
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: Amanda A Fox; Charles D Collard; Stanton K Shernan; Christine E Seidman; Jonathan G Seidman; Kuang-Yu Liu; Jochen D Muehlschlegel; Tjorvi E Perry; Sary F Aranki; Christoph Lange; Daniel S Herman; Thomas Meitinger; Peter Lichtner; Simon C Body Journal: Anesthesiology Date: 2009-04 Impact factor: 7.892
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