Gene Variation of Endoplasmic Reticulum Aminopeptidase 1 and Risk ofIncident Type 2 Diabetes Mellitus amongst 22,718 Initially HealthyWomen

摘要

Objective: Recent studies have demonstrated the importance of Endoplasmic ReticulumAminopeptidase 1 (ERAP1) gene variants in inflammatory conditions, including Type 1 diabetes melli-tus. However, to date, no large prospective, genetic-epidemiological data are available on the relevanceof ERAP1 genetic variation in the risk of non-insulin dependent diabetes. Methods: The association between 33 tag-SNPs (tSNPs) of ERAP1 and incident Type 2 Diabetes melli-tus (T2D) was investigated in 22,718 Caucasian female participants of the prospective Women's Ge-nome Health Study. All were free of known cancer, cardiovascular disease, and diabetes mellitus atbaseline. During an 18-year follow-up period, 1,927 newly diagnosed first ever T2D were identified.Multivariable Cox regression analysis was performed to investigate the relationship between genotypesand T2D risk assuming an additive genetic model. Results: None of the gene variants evaluated were associated with T2D risk. Conclusions: If corroborated in other large prospective studies, the present findings suggest that geneticvariation within the ERAP1 gene locus may not be useful prognostic indicators for risk assessment oftype 2 diabetes mellitus.