Human Molecular Genetics Advance Access published online on April 18, 2009
Human Molecular Genetics, doi:10.1093/hmg/ddp169
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The T-381C SNP in BNP gene may be modestly associated with type 2 diabetes: an updated meta-analysis in 49,279 subjects
1 CNRS-8090-Institute of Biology, Pasteur Institute, Lille, France 2 CHU de Poitiers, Endocrinologie Diabetologie, CIC INSERM 0802, INSERM U927, Université de Poitiers, UFR Médecine Pharmacie, Poitiers, France 3 Department of Surgery and Internal Medicine, Clinic Lindberg, medical departement, Winterthur and University of Berne, Switzerland 4 Department of Endocrinology-Diabetology, Centre Hospitalier Sud-Francilien, Corbeil-Essonnes, France 5 Diabétologie et Métabolisme, Centre Hospitalier Universitaire Vaudois (CHUV) BH19, Lausanne, Switzerland 6 INSERM U557/U1125 Inra/Cnam/University paris, Bobigny, France 7 INSERM, U695, Paris, France 8 Faculty of Medicine Xavier Bichat, University Denis Diderot, Paris, France 9 Assistance Publique-Hôpitaux de Paris, Bichat Hospital, Diabetology-Endocrinology-Nutrition, Paris, France 10 Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan 48109, USA 11 Department of Laboratory Medicine, Paracelsus Medical University and Landeskrankenhaus Salzburg, Salzburg, Austria 12 Department of Internal Medicine, Krankenhaus Hallein, A-5400 Hallein, Austria 13 Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA 14 Center for Human genetic Research, Massachusetts General Hospital, Boston, Massachusetts 02114, USA 15 Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA 16 Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA 17 Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA 18 Department of Clinical Sciences, Diabetes and Endocrinology Research Unit, University Hospital Malmö, Lund University, S-205 02 Malmö, Sweden 19 Department of Medicine, Helsinki University Hospital, University of Helsinki, FIN-00300 Helsinki, Finland 20 deCODE Genetics, 101 Reykjavik, Iceland 21 INSERM U780-IFR69, University Paris Sud, Villejuif, France 22 Department of Genomic Medicine, Hammersmith Hospital, Imperial College London, London, UK
* Corresponding author: Philippe Froguel, Genomic Medecine, Hammersmith Hospital, Imperial College London, Du Cane Road, London, W12 ONN, UK. Tel: +44 02083833989; Email: p.froguel{at}imperial.ac.uk
Received January 22, 2009; Revised March 27, 2009; Accepted April 3, 2009
A recent study reported an association between the brain natriuretic peptide (BNP) promoter T-381C polymorphism (rs198389) and protection against type 2 diabetes (T2D). As replication in several studies is mandatory to confirm genetic results, we analyzed the T-381C polymorphism in seven independent case control cohorts and in 291 T2D-enriched pedigrees totalling 39,557 subjects of European origin. A meta-analysis of the seven case-control studies (N=39,040) showed a nominal protective effect (Odds ratio (OR)=0.86 [0.79-0.94], P=0.0006) of the CC genotype on T2D risk, consistent with the previous study. By combining all available data (N=49,279), we further confirmed a modest contribution of the BNP T-381C polymorphism for protection against T2D (OR=0.86 [0.80-0.92], P=1.4 x 10–5). Potential confounders such as gender, age, obesity status or family history were tested in 4,335 T2D and 4,179 normoglycemic (NG) subjects and they had no influence on T2D risk. This study provides further evidence of a modest contribution of the BNP T-381C polymorphism in protection against T2D and illustrates the difficulty of unambiguously proving modest-sized associations even with large sample sizes.