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Studies of the relationship between the ENPP1 K121Q polymorphism and type 2 diabetes, insulin resistance and obesity in 7,333 Danish white subjects.
- Source :
- Diabetologia; Sep2006, Vol. 49 Issue 9, p2097-2104, 8p, 1 Diagram, 3 Charts
- Publication Year :
- 2006
-
Abstract
- Aims/hypothesis Plasma cell membrane glycoprotein 1 (PC-1) inhibits insulin signalling by direct interaction with the insulin receptor a 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<superscript>-6</superscript>). 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 0012186X
- Volume :
- 49
- Issue :
- 9
- Database :
- Complementary Index
- Journal :
- Diabetologia
- Publication Type :
- Academic Journal
- Accession number :
- 21805876
- Full Text :
- https://doi.org/10.1007/s00125-006-0353-x