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No evidence of association of ENPP1 variants with type 2 diabetes or obesity in a study of 8,089 U.K. Caucasians

Lookup NU author(s): Professor Mark Walker


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Ectoenzyme nucleotide pyrophosphate phosphodiesterase 1 (ENPP1) is an inhibitor of insulin-induced activation of the insulin receptor. There is strong evidence from several previous studies that a common coding variant of ENPP1 (K121Q) and a three-marker haplotype (Q121, IVS20delT-11, and G+1044TGA) are associated with type 2 diabetes and obesity. We examined the impact of ENPP1 variation on type 2 diabetes and obesity in a large U.K. genetic association study. We genotyped the three previously associated polymorphisms in 2,363 type 2 diabetic case and 4,045 control subjects, as well as 1,681 subjects from 529 type 2 diabetic families. We used the same subjects for morbid and moderate obesity association studies. For type 2 diabetes, moderate and morbid obesity, and for both the Q121 and three-marker haplotype, our results exclude with >95% confidence the effect sizes from previous studies (Q121 allele: odds ratio 1.02 [95% CI 0.93-1.12], P = 0.61; 1.00 [0.85-1.18], P = 0.99; and 0.92 [0.70-1.20], P = 0.41; three-marker haplotype: 1.10 [0.96-1.26], P = 0.17; 0.97 [0.77-1.23], P = 0.81; and 0.86 [0.57-1.30], P = 0.46 for type 2 diabetes, moderate, and morbid obesity, respectively). A K121Q type 2 diabetes meta-analysis of all previously published studies remained significant after the inclusion of this study (1.25 [1.10-1.43], P = 0.0007), although there was some evidence of publication bias. In conclusion, we find no evidence that previously associated variants of ENPP1 are associated with type 2 diabetes or obesity in the U.K. population. © 2006 by the American Diabetes Association.

Publication metadata

Author(s): Weedon MN, Shields B, Hitman G, Walker M, McCarthy MI, Hattersley AT, Frayling TM

Publication type: Article

Publication status: Published

Journal: Diabetes

Year: 2006

Volume: 55

Issue: 11

Pages: 3175-3179

ISSN (print): 0012-1797

ISSN (electronic): 1939-327X

Publisher: American Diabetes Association


DOI: 10.2337/db06-0410

PubMed id: 17065358


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Funder referenceFunder name
068545/Z/02Wellcome Trust
G0500070Medical Research Council
G0000934Medical Research Council