ENPP1 K121Q polymorphism and obesity, hyperglycaemia and type 2 diabetes in the prospective DESIR Study
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AIMS/HYPOTHESIS: We assessed the predictive value of ectonucleotide pyrophosphatase/phosphodiesterase 1 gene (ENPP1) SNPs with regard to the risk of developing obesity and/or type 2 diabetes in a large French general population. METHODS: We genotyped the ENPP1 SNPs K121Q (rs1044498), IVS20delT-11 (rs1799774) and A/G+1044TGA (rs7754561) in 5,153 middle-aged participants of the Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR) cohort. RESULTS: At baseline, the K121Q polymorphism was not associated either with BMI (p = 0.98) or with class I obesity (odds ratio [OR] 0.99, p = 0.81), but showed a borderline association with class II obesity (OR 1.65, p = 0.02). The K121Q variant was not associated with any trait during the 9-year follow-up. Pooled analyses both at baseline and at follow-up failed to show any association with hyperglycaemia (OR 1.08, p = 0.28) or type 2 diabetes (OR 1.15, p = 0.38). However, we did show an association of the Q121 allele with the risk of hyperglycaemia (OR 1.45, p = 0.001; n = 265) and type 2 diabetes (OR 1.65, p = 0.01; n = 103) in participants reporting a family history of type 2 diabetes. These results did not remain significant after a Bonferroni correction. The IVS20delT-11 and A/G+1044TGA polymorphisms and the three-allele risk haplotype (K121Q, IVS20delT-11 and A-->G+1044TGA [QdelTG]) were not associated with any trait, either at baseline or at follow-up. CONCLUSIONS/INTERPRETATION: In a general French population we did not find an association of the QdelTG risk haplotype with adult obesity and type 2 diabetes. We detected nominal evidence of association between the K121Q polymorphism and both severe adult obesity at baseline and the risk of hyperglycaemia or type 2 diabetes in participants with a family history of type 2 diabetes in pooled analyses both at baseline and follow-up.
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