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

Weedon, M; Shields, B; Hitman, G; Walker, M; McCarthy, M; Hattersley, A; Frayling, T

Journal article

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

Abstract:: 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.

Publication status:: Published

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APA Style

Weedon, M., Shields, B., Hitman, G., Walker, M., McCarthy, M., Hattersley, A., & Frayling, T. (2006). No evidence of association of ENPP1 variants with type 2 diabetes or obesity in a study of 8,089 U.K. Caucasians. Diabetes, 55(11), 3175–3179.

MLA Style

Weedon, M., et al. “No Evidence of Association of ENPP1 Variants with Type 2 Diabetes or Obesity in a Study of 8,089 U.K. Caucasians.” Diabetes, vol. 55, no. 11, 2006, pp. 3175–79.

Chicago Style

Weedon, M, B Shields, G Hitman, M Walker, M McCarthy, A Hattersley, and T Frayling. 2006. “No Evidence of Association of ENPP1 Variants with Type 2 Diabetes or Obesity in a Study of 8,089 U.K. Caucasians.” Diabetes 55 (11): 3175–79.
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