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

CNRS-8090-Institute of Biology, Pasteur Institute, Lille, France.
Human Molecular Genetics (Impact Factor: 6.39). 05/2009; 18(13):2495-501. DOI: 10.1093/hmg/ddp169
Source: PubMed


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 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.

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    • "BNP-Tg mice ↑ BNP ↓ body weight ↓ visceral and subcutaneous fat mass ↓ diet-induced ectopic fat accumulation ↑ glucose tolerance ↑ muscle mitochondrial content ↑ lipid oxidation rate Miyashita et al., 2009 cGK-Tg mice ↑ cGMP ↓ body weight ↓ visceral and subcutaneous fat mass ↓ diet-induced ectopic fat accumulation ↑ glucose tolerance ↑ muscle mitochondrial content ↑ lipid oxidation rate Miyashita et al., 2009 GC-A+/− mice ↓ cGMP-signaling ↑ body weight ↑ fat mass ↓ glucose tolerance Miyashita et al., 2009 BNP promoter T-381C polymorphism (humans) ↑ BNP ↓ blood glucose levels ↓ T2DM-risk Meirhaeghe et al., 2007 Choquet et al., 2009 rs5068 (humans) ↑ ANP "
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