التفاصيل البيبلوغرافية
| العنوان: |
Genetic Variants Contribute to Phenotypic Heterogeneity of Type 1 Diabetes. |
| المؤلفون: |
Redondo, Maria J., Geyer, Susan, Steck, Andrea K., Sosenko, Jay, Anderson, Mark, Antinozzi, Peter, Michels, Aaron, Wentworth, John, Ping Xu, Pugliese, Alberto, Xu, Ping, Type 1 Diabetes TrialNet Study Group |
| المصدر: |
Diabetes Care; Feb2018, Vol. 41 Issue 2, p311-317, 7p |
| مصطلحات موضوعية: |
PHENOTYPES, TYPE 1 diabetes, TRANSCRIPTION factors, SINGLE nucleotide polymorphisms, DIAGNOSIS of diabetes, ALLELES, COMPARATIVE studies, DISEASE susceptibility, GENETIC polymorphisms, GENETICS, LONGITUDINAL method, RESEARCH methodology, MEDICAL cooperation, PROTEINS, RESEARCH, EVALUATION research |
| مستخلص: |
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 (SNPs) 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 immunologic and metabolic phenotype at type 1 diabetes diagnosis, which could be partly driven by type 2 diabetes-like pathogenic mechanisms. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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