التفاصيل البيبلوغرافية
| العنوان: |
Transcription Factor 7-Like 2 (TCF7L2) Gene Polymorphism and Progression From Single to Multiple Autoantibody Positivity in Individuals at Risk for Type 1 Diabetes |
| المؤلفون: |
Redondo, Maria J, Steck, Andrea K, Sosenko, Jay, Anderson, Mark, Antinozzi, Peter, Michels, Aaron, Wentworth, John M, Atkinson, Mark A, Pugliese, Alberto, Geyer, Susan, Group, the Type 1 Diabetes TrialNet Study |
| المصدر: |
Diabetes Care, vol 41, iss 12 |
| بيانات النشر: |
eScholarship, University of California |
| سنة النشر: |
2018 |
| المجموعة: |
University of California: eScholarship |
| مصطلحات موضوعية: |
Biomedical and Clinical Sciences, Health Sciences, Prevention, Genetics, Autoimmune Disease, Nutrition, Diabetes, Aetiology, 2.1 Biological and endogenous factors, Metabolic and endocrine, Adolescent, Adult, Antibody Specificity, Autoantibodies, Autoimmunity, Child, Preschool, Cohort Studies, Diabetes Mellitus, Type 1, Disease Progression, Female, Gene Frequency, Genetic Predisposition to Disease, Humans, Infant, Male, Middle Aged, Obesity, Overweight |
| الوصف: |
ObjectiveThe type 2 diabetes-associated alleles at the TCF7L2 locus mark a type 1 diabetes phenotype characterized by single islet autoantibody positivity as well as lower glucose and higher C-peptide measures. Here, we studied whether the TCF7L2 locus influences progression of islet autoimmunity, from single to multiple (≥2) autoantibody positivity, in relatives of patients with type 1 diabetes.Research design and methodsWe evaluated 244 participants in the Type 1 Diabetes TrialNet Pathway to Prevention study with confirmed single autoantibody positivity at screening and Immunochip single nucleotide polymorphism data (47.5% male; median age 12.8 years, range 1.2-45.9; 90.2% white). We analyzed risk allele frequency at TCF7L2 rs4506565 (in linkage disequilibrium with rs7903146). Altogether, 62.6% participants carried ≥1 risk allele. Univariate and multivariable Cox proportional hazards models and Kaplan-Meier statistical methods were used.ResultsDuring follow-up (median 5.2 years, range 0.2-12.6), 62% of the single autoantibody-positive participants developed multiple autoantibody positivity. In the overall cohort, the TCF7L2 locus did not significantly predict progression to multiple autoantibody positivity. However, among single GAD65 autoantibody-positive participants (n = 158), those who carried ≥1 risk allele had a lower rate of progression to multiple autoantibody positivity (hazard ratio [HR] 0.65, P = 0.033) than those who did not, after adjustment for HLA risk haplotypes and age. Among subjects who were either IA-2 or insulin autoantibody positive only, carrying ≥1 TCF7L2 risk allele was not a significant factor overall, but in overweight or obese participants, it increased the risk of progression to multiple autoantibody positivity (HR 3.02, P = 0.016) even with adjustment for age.ConclusionsThe type 2 diabetes-associated TCF7L2 locus influences progression of islet autoimmunity, with differential effects by autoantibody specificity and interaction by obesity/overweight. |
| نوع الوثيقة: |
article in journal/newspaper |
| وصف الملف: |
application/pdf |
| اللغة: |
unknown |
| العلاقة: |
qt8qs5877s; https://escholarship.org/uc/item/8qs5877sTest |
| الإتاحة: |
https://escholarship.org/uc/item/8qs5877sTest |
| حقوق: |
public |
| رقم الانضمام: |
edsbas.97061EC4 |
| قاعدة البيانات: |
BASE |
