Journal
OBESITY
Volume 17, Issue 8, Pages 1549-1553Publisher
WILEY
DOI: 10.1038/oby.2009.75
Keywords
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Funding
- FONDACOEUR charity
- le Conseil Regional Nord Pas de Calais/FEDER
- INSERM
- CNAMTS
- Lilly
- Novartis Pharma
- Sanofi-Aventis
- Association Diabete Risque Vasculaire
- Federation Francaise de Cardiologie
- La Fondation de France
- ALFEDIAM
- ONIVINS
- Ardix Medical
- Bayer Diagnostics
- Becton Dickinson
- Cardionics
- Merck Sante
- Novo Nordisk
- Pierre Fabre
- Roche
- Topcon
- UK Medical Research Council
- Medical Research Council [G0600331] Funding Source: researchfish
- MRC [G0600331] Funding Source: UKRI
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Visfatin was recently reported as a novel adipokine encoded by the NAMPT (PBEF1) gene. This study was aimed at investigation of the possibility that single-nucleotide polymorphisms (SNPs) in the visfatin gene are associated with either obesity or type 2 diabetes (T2D). A set of eight tag-SNPs were selected and ABI SNPlex assays designed for genotyping purposes. A total of 1,709 severely obese subjects were typed (896 class III obese adults and 813 children) together with 2,367 T2D individuals and 2,850 controls. For quantitative trait analysis, an additional 2,362 subjects were typed for rs10487818 from a general population sample. One rare SNP, rs10487818, located in intron 4 of NAMPT was associated with severe obesity, with a minor allele frequency of 1.6% in controls, 0.4% in the class III obese adults and, remarkably, 0% in the severely obese children. A highly significant association was observed for the presence or absence of the rare allele, i.e., (A, A) vs. (A, T + T, T) genotypes, in children (P = 6 x 10(-9)) and in adults (P = 8 x 10(-5)). No other significant (P < 0.05) association was observed with obesity or T2D for this or any other SNP. No association with BMI or waist-to-hip ratio was observed in a general population sample (n = 5,212). This is one of the first rare SNPs shown to be protective against a common polygenic disease and provides further evidence that rare alleles of strong effect can contribute to complex diseases such as severe obesity.
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