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Association between the T-381C polymorphism of the brain natriuretic peptide gene and risk of type 2 diabetes in human populations

Lookup NU author(s): Professor Mark Walker


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Brain natriuretic peptide (BNP/NPPB) is a member of the natriuretic family involved in the regulation of blood pressure and blood volume as well as lipolysis control in human fat cells. Thus BNP may play a role in energy metabolism and metabolic diseases. We therefore assessed the association between the BNP promoter T-381C polymorphism and risk of type 2 diabetes and metabolic and BNP expression traits in several population samples. In French population-based samples (n = 3216), we found that individuals bearing the -381CC genotype had lower (P = 0.005) fasting glucose levels than -381TC or -381TT individuals. Moreover, the -381CC genotype was less frequent in individuals with type 2 diabetes (n = 280, 13.6%) or with impaired fasting glucose (n = 248, 12.9%) compared with normoglycaemic individuals (n = 2485, 17.8%). The adjusted odds ratio (OR) (95% CI) of type 2 diabetes for -381CC individuals was 0.69 (0.47-1.00), P = 0.05, when compared with -381T allele bearers. We replicated this association in four additional case-control studies for type 2 diabetes. The overall OR (95% CI) of type 2 diabetes was 0.85 (0.76-0.96), P = 0.008, (under a recessive model) (3593 cases and 6646 controls in total). We also found that the -381C allele was associated with higher plasma BNP concentrations (P = 0.015, n 5 634) and higher BNP promoter activity in reporter gene assays. Collectively, these data suggest that relatively high BNP expression may protect against type 2 diabetes in humans. © The Author 2007. Published by Oxford University Press. All rights reserved.

Publication metadata

Author(s): Meirhaeghe A, Sandhu MS, McCarthy MI, de Groote P, Cottel D, Arveiler D, Ferrieres J, Groves CJ, Hattersley AT, Hitman GA, Walker M, Wareham NJ, Amouyel P

Publication type: Article

Publication status: Published

Journal: Human Molecular Genetics

Year: 2007

Volume: 16

Issue: 11

Pages: 1343-1350

Print publication date: 01/06/2007

ISSN (print): 0964-6906

ISSN (electronic): 1460-2083

Publisher: Oxford University Press


DOI: 10.1093/hmg/ddm084


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Funder referenceFunder name
068545/z/02Wellcome Trust
MC_U106179471Medical Research Council