1. Association of TCF7L2 variation with single islet autoantibody expression in children with type 1 diabetes
- Author
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Michael L. Metzker, Jesse Muniz, Ashok Balasubramanyam, Christiane S. Hampe, Luisa M. Rodriguez, Struan F.A. Grant, Dinakar Iyer, Maria J. Redondo, Morey W. Haymond, and Fariba Vaziri-Sani
- Subjects
medicine.medical_specialty ,endocrine system ,endocrine system diseases ,Transcription Factor ,Endocrinology, Diabetes and Metabolism ,030209 endocrinology & metabolism ,Type 2 diabetes ,Endocrinology and Diabetes ,medicine.disease_cause ,Autoimmunity ,03 medical and health sciences ,0302 clinical medicine ,Diabetes mellitus ,Internal medicine ,Medicine ,030304 developmental biology ,Autoantibodies ,0303 health sciences ,Type 1 diabetes ,geography ,geography.geographical_feature_category ,business.industry ,Autoantibody ,nutritional and metabolic diseases ,Genetics/Genomes/Proteomics/Metabolomics ,Pediatric Type 1 Diabetes ,medicine.disease ,Islet ,3. Good health ,Endocrinology ,Zinc Transporter 8 ,Immunology ,business ,TCF7L2 ,LADA (Latent Autoimmune Diabetes in Adults) - Abstract
Background The transcription factor 7-like 2 (TCF7L2) gene has the strongest genetic association with type 2 diabetes. TCF7L2 also associates with latent autoimmune diabetes in adults, which often presents with a single islet autoantibody, but not with classical type 1 diabetes. Methods We aimed to test if TCF7L2 is associated with single islet autoantibody expression in pediatric type 1 diabetes. We studied 71 prospectively recruited children who had newly diagnosed type 1 diabetes and evidence of islet autoimmunity, that is, expressed ≥1 islet autoantibody to insulin, glutamic acid decarboxylase 65, islet cell autoantigen 512, or zinc transporter 8. TCF7L2 rs7903146 alleles were identified. Data at diagnosis were cross-sectionally analyzed. Results We found that 21.1% of the children with autoimmune type 1 diabetes expressed a single islet autoantibody. The distribution of TCF7L2 rs7903146 genotypes in children with a single autoantibody (n=15) was 40% CC, 26.7% CT and 33.3% TT, compared with children with ≥2 islet autoantibodies (50% CC, 42.9% CT and 7.1% TT, p=0.024). Furthermore, compared with children with ≥2 autoantibodies, single-autoantibody children had characteristics reflecting milder autoimmune destruction of β-cells. Restricting to lean children (body mass index
- Published
- 2014