The Association of HLA Class II, CTLA-4 and PTPN22 Genetic Polymorphisms and β-Cell Autoantibodies in Development of Type I Diabetes in Patients with Autoimmune Thyroid Disease (CROSBI ID 644480)
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Podaci o odgovornosti
Rojnić Putarek, Nataša ; Grubić, Zorana ; Grčević, Danka ; Kušec, Vesna ; Knežević-Ćuća, Jadranka ; Krnić, Nevena ; Špehar Uroić, Anita ; Baretić, Maja ; Dumić, Miroslav
engleski
The Association of HLA Class II, CTLA-4 and PTPN22 Genetic Polymorphisms and β-Cell Autoantibodies in Development of Type I Diabetes in Patients with Autoimmune Thyroid Disease
Background: Co-occurrence of type 1 diabetes (T1D) and autoimmune thyroid disease (AITD) denote variant of autoimmune polyglandular syndrome type 3 (APS3v). Thyroid autoimmunity in T1D was widely studied, but a few studies examined β-cell autoimmunity among AITD patients. Several susceptibility genes for APS3v have been identified: HLA class II, CTLA-4 and PTPN22 gene. Objective and hypotheses: To investigate β-cell autoimmunity and genetic polymorphism of HLA class II, CTLA-4 and PTPN22 genes in AITD patients. Method: The study comprised of 158 unrelated AITD patients (127 with autoimmune thyroiditis, AT and 31 with Graves disease, GD) aged 4.3–25.9 years and 94 healthy control subjects aged 4.7–21.5 years. Islet cell cytoplasmic (ICA), glutamic acid decarboxylase (GADA) and thyrosin phosphatase islet (IA-2) autoantibodies as well as HLA-DRB1, - DQB1 alleles, A49G CTLA-4, C60T CTLA-4 and R620W PTPN22 gene polymorphisms were analyzed. Results: β-cell autoimmunity was found in 10.76% (17/158) AITD patients, significantly more than in controls (0%, 0/94 ; P=0.001), with higher prevalence found in AT (11.81%, 15/127) than GD (6.45%, 2/31) patients. All three β-cell autoantibodies were positive in three patients, and three patients were positive for two autoantibodies. All six of them developed T1D during the investigation period of 2.5 years. No difference in high risk HLA haplotypes for development of T1D was found between the groups. However, low risk HLA haplotypes for development of T1D were found more frequently in controls than in AITD patients (69.9% vs 31.3%, P=0.003). Disease associated G/G genotype of CTLA-4 A49G gene was significantly more common in AITD patient with β-cell autoimmunity than in controls (P=0.024), while there were no differences in PTPN22 and C60T CTLA- 4 gene polymorphisms between groups. Conclusion: Patients with AITD are prone to develop β-cell autoimmunity and T1D, especially those with multiple islet autoantibodies and G/G genotype of CTLA-4 A49G gene
type 1 diabetes ; autoimmune thyroid disease ; autoimmunity
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Podaci o prilogu
190-x.
2016.
nije evidentirano
objavljeno
Podaci o matičnoj publikaciji
Hormone Research in Paediatrics
1663-2818
Podaci o skupu
55th Annual ESPE (The European Society for Paediatric Endocrinology) Meeting
poster
10.09.2016-12.09.2016
Pariz, Francuska
Povezanost rada
Kliničke medicinske znanosti