Journal Article

The T-381C SNP in <i>BNP</i> gene may be modestly associated with type 2 diabetes: an updated meta-analysis in 49 279 subjects

Hélène Choquet, Christine Cavalcanti-Proença, Cécile Lecoeur, Christian Dina, Stéphane Cauchi, Martine Vaxillaire, Samy Hadjadj, Fritz Horber, Natasha Potoczna, Guillaume Charpentier, Juan Ruiz, Serge Hercberg, Suliya Maimaitiming, Ronan Roussel, Michael Boenhnke, Anne U. Jackson, Wolfgang Patsch, Franz Krempler, Benjamin F. Voight, David Altshuler, Leif Groop, Gudmar Thorleifsson, Valgerdur Steinthorsdottir, Kari Stefansson, Beverley Balkau, Philippe Froguel and David Meyre

in Human Molecular Genetics

Volume 18, issue 13, pages 2495-2501
Published in print July 2009 | ISSN: 0964-6906
Published online April 2009 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddp169
The T-381C SNP in BNP gene may be modestly associated with type 2 diabetes: an updated meta-analysis in 49 279 subjects

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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 × 10−5]. Potential confounders such as gender, age, obesity status or family history were tested in 4335 T2D and 4179 normoglycemic 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.

Journal Article.  3925 words.  Illustrated.

Subjects: Genetics and Genomics

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