TCF7L2 genetic variants contribute to phenotypic heterogeneity of type 1 diabetes
- Author(s)
- Redondo, MJ; Geyer, S; Steck, AK; Sosenko, J; Anderson, M; Antinozzi, P; Michels, A; Wentworth, J; Xu, P; Pugliese, A; and the Type 1 Diabetes TrialNet Study, Group;
- Journal Title
- Diabetes Care
- Publication Type
- Journal Article
- Abstract
- OBJECTIVE: The phenotypic diversity of type 1 diabetes suggests heterogeneous etiopathogenesis. We investigated the relationship of type 2 diabetes-associated transcription factor 7 like 2 (TCF7L2) single nucleotide polymorphisms (SNP) with immunologic and metabolic characteristics at type 1 diabetes diagnosis. RESEARCH DESIGN AND METHODS: We studied TrialNet participants with newly diagnosed autoimmune type 1 diabetes with available TCF7L2 rs4506565 and rs7901695 SNP data (n = 810; median age 13.6 years; range 3.3-58.6). We modeled the influence of carrying a TCF7L2 variant (i.e., having 1 or 2 minor alleles) on the number of islet autoantibodies and oral glucose tolerance test (OGTT)-stimulated C-peptide and glucose measures at diabetes diagnosis. All analyses were adjusted for known confounders. RESULTS: The rs4506565 variant was a significant independent factor of expressing a single autoantibody, instead of multiple autoantibodies, at diagnosis (odds ratio [OR] 1.66 [95% CI 1.07, 2.57], P = 0.024). Interaction analysis demonstrated that this association was only significant in participants >/=12 years old (n = 504; OR 2.12 [1.29, 3.47], P = 0.003) but not younger ones (n = 306, P = 0.73). The rs4506565 variant was independently associated with higher C-peptide area under the curve (AUC) (P = 0.008) and lower mean glucose AUC (P = 0.0127). The results were similar for the rs7901695 SNP. CONCLUSIONS: In this cohort of individuals with new-onset type 1 diabetes, type 2 diabetes-linked TCF7L2 variants were associated with single autoantibody (among those >/=12 years old), higher C-peptide AUC, and lower glucose AUC levels during an OGTT. Thus, carriers of the TCF7L2 variant had a milder immunological and metabolic phenotype at type 1 diabetes diagnosis, which could be partly driven by type 2 diabetes-like pathogenic mechanisms.
- Publisher
- American Diabetes Association
- Research Division(s)
- Population Health And Immunity
- PubMed ID
- 29025879
- Publisher's Version
- https://doi.org/10.2337/dc17-0961
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2017-10-16 02:00:14
Last Modified: 2017-10-16 04:54:40