Human Molecular Genetics Advance Access published online on April 5, 2007
Human Molecular Genetics, doi:10.1093/hmg/ddm084
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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
1 INSERM, U744, Lille; Institut Pasteur de Lille, Lille; Université de Lille 2, Lille, France 2 Department of Public Health & Primary Care, Institute of Public Health, University of Cambridge, Strangeways Research Laboratory, Cambridge, U.K. 3 MRC Epidemiology Unit, Strangeways Research Laboratory, Cambridge, U.K. 4 Diabetes Research Laboratories, Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, U.K. 5 Service de cardiologie C, Hôpital cardiologique, CHRU Lille, Lille, France 6 Department of Epidemiology and Public Health, Faculty of Medicine, Strasbourg, France 7 INSERM, U558, Faculté de Médecine, Toulouse, France 8 Department of Diabetes and Vascular Medicine, Peninsula Medical School, Exeter, U.K. 9 Department of Diabetes and Metabolic Medicine, Barts and the London, Queen Mary's School of Medicine and Dentistry, University of London, London, U.K. 10 Department of Medicine, School of Medicine, Newcastle University, Newcastle upon Tyne, U.K.
* Corresponding author : Aline Meirhaeghe, INSERM U744, Institut Pasteur de Lille, 1 rue du Pr. Calmette, BP 245, 59019 LILLE Cedex, France. Tel : + 33 3 20 87 73 91, Fax : +33 3 20 87 78 94. e-mail: aline.meirhaeghe-hurez{at}pasteur-lille.fr
Received January 23, 2007; Revised March 27, 2007; Accepted March 27, 2007
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 [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 4 additional case-control studies for type 2 diabetes. The overall odds ratio [95% CI] of type 2 diabetes was 0.85 [0.76-0.96], p=0.008 (under a recessive model) (3,593 cases and 6,646 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.
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