title: ENPP1 K121Q polymorphism and obesity, hyperglycaemia and type 2 diabetes in the prospective DESIR Study.
abstract: OBJECTIVE
  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
  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.
authors: CNRS 8090-Institute of Biology, Pasteur Institute, Lille, France.
authors: D
authors: D
authors: Meyre
authors: N
authors: N
authors: Bouatia-Naji
authors: V
authors: V
authors: Vatin
authors: J
authors: J
authors: Veslot
authors: C
authors: C
authors: Samson
authors: J
authors: J
authors: Tichet
authors: M
authors: M
authors: Marre
authors: B
authors: B
authors: Balkau
authors: P
authors: P
authors: Froguel
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D002874:Chromosome Mapping; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006801:Humans; D006943:Hyperglycemia / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D009765:Obesity / Q000150:complications / Q000235:genetics; D050177:Overweight / Q000235:genetics; D010727:Phosphoric Diester Hydrolases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D011755:Pyrophosphatases / Q000235:genetics*
chemical_list: D001786:Blood Glucose; D010727:Phosphoric Diester Hydrolases; C065962:ectonucleotide pyrophosphatase phosphodiesterase 1; D011755:Pyrophosphatases
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