Studies of the relationship between the ENPP1 K121Q polymorphism and type 2 diabetes, insulin resistance and obesity in 7,333 Danish white subjects |
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Authors: | N Grarup S A Urhammer J Ek A Albrechtsen C Glümer K Borch-Johnsen T Jørgensen T Hansen O Pedersen |
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Institution: | (1) Steno Diabetes Center and Hagedorn Research Institute, Niels Steensens Vej 2-6, NSP1.14, 2820 Gentofte, Copenhagen, Denmark;(2) Clinic of Endocrinology and Cardiology, Frederiksberg University Hospital, Frederiksberg, Denmark;(3) Kennedy Institute-National Eye Clinic, Glostrup, Denmark;(4) Research Centre for Prevention and Health, Glostrup University Hospital, Glostrup, Denmark;(5) Faculty of Health Science, University of Aarhus, Aarhus, Denmark |
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Abstract: | Aims/hypothesis Plasma cell membrane glycoprotein 1 (PC-1) inhibits insulin signalling by direct interaction with the insulin receptor α subunit. This inhibition is enhanced by the minor Q allele of the K121Q polymorphism (rs1044498) in the gene (ENPP1) encoding PC-1. This polymorphism has been studied in relation to insulin resistance, type 2 diabetes and obesity in several populations with conflicting results. We assessed the impact of the ENPP1 K121Q polymorphism on type 2 diabetes, obesity and quantitative metabolic traits in 7,333 Danes.Subjects and methods The K121Q polymorphism was genotyped in the population-based Inter99 study cohort (5,961 subjects) and in a group of 1,386 patients with type 2 diabetes. All subjects were Danish whites.Results No significant associations with type 2 diabetes or related quantitative metabolic traits, including measures of insulin resistance, were detected. However, a meta-analysis of the present and published studies revealed an association with type 2 diabetes (odds ratio per Q allele, 1.17 95% CI 1.10–1.25], p=1×10−6). In case–control studies comparing subjects of different BMI strata, we observed a putative association of the codon 121 QQ genotype with being overweight (BMI>25 kg/m2; odds ratio 1.63 95% CI 1.09–2.46], p=0.015), an association not observed when comparing other levels of BMI or when analysing BMI as a quantitative trait.Conclusions/interpretation In a meta-analysis, the ENPP1 codon 121 Q allele associates with type 2 diabetes. However, a similar association was not found in the present study of Danish white subjects. The effect of this variant on obesity in Danish subjects is contentious and further study is needed. |
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Keywords: | ENPP1 Genetic epidemiology K121Q polymorphism Insulin resistance Meta-analysis Obesity Plasma cell membrane glycoprotein 1 Type 2 diabetes |
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