Journal Article

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

Aline Meirhaeghe, Manjinder S. Sandhu, Mark I. McCarthy, Pascal de Groote, Dominique Cottel, Dominique Arveiler, Jean Ferrières, Christopher J. Groves, Andrew T. Hattersley, Graham A. Hitman, Mark Walker, Nicholas J. Wareham and Philippe Amouyel

in Human Molecular Genetics

Volume 16, issue 11, pages 1343-1350
Published in print June 2007 | ISSN: 0964-6906
Published online April 2007 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddm084
Association between the T-381C polymorphism of the brain natriuretic peptide gene and risk of type 2 diabetes in human populations

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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 = 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.

Journal Article.  4901 words.  Illustrated.

Subjects: Genetics and Genomics

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