Association of TNF-α, CTLA4, and PTPN22 polymorphisms with type 1 diabetes and other autoimmune diseases in Brazil

• Published in: Genetics and molecular research 2015-12, Vol.14 (4), p.18936-18944
• Main Authors: Tavares, N A C, Santos, M M S, Moura, R, Araújo, J, Guimarães, R L, Crovella, S, Brandão, L A C
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Age of Onset; Brazil; Child; CTLA-4 Antigen - genetics; Diabetes Mellitus, Type 1 - genetics; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Polymorphism, Single Nucleotide; Protein Tyrosine Phosphatase, Non-Receptor Type 22 - genetics; Sequence Analysis, DNA; Tumor Necrosis Factor-alpha - genetics; Young Adult
• ISSN: 1676-5680; 1676-5680
• DOI: 10.4238/2015.December.28.42

Type 1 diabetes mellitus (T1D) is a complex disorder characterized by an autoimmune response against human pancreatic beta-cells. Patients with T1D can also develop a response toward one or more other factors, such as in autoimmune thyroiditis (AITD) and celiac disease (CD). In the presence of T1D + AITD, the patient is diagnosed with autoimmune polyglandular syndrome type III (APSIII); patients with APSIII may also present with CD. These diseases have a strong genetic component and share many susceptibility genes, suggesting potentially overlapping pathogenic pathways. Polymorphisms in the TNF-α(rs1800629), CTLA-4 (rs231775), and PTPN22 (rs2476601) genes have been previous associated with T1D; however, there is no consensus regarding their role in T1D and scarce literature focusing on AIDT and/or CD. Thus, we analyzed these genetic variants in 205 Northeast Brazilian patients with T1D and with/without AITD and/or CD, and in 308 healthy controls. The PTPN22 gene variants were associated with T1D susceptibility and APSIII [odds ratio (OR) = 2.57 and 2.77, respectively]. CTLA4 rs231775 and TNF-αrs1800629 were not associated with T1D onset in the Brazilian population. However, when comparing APSIII individuals in the T1D only group, we observed an association of the TNF-αSNP in the allelic (P = 0.0442; OR = 0.44) and dominant models (P = 0.0387; OR = 0.40). This study reinforces the importance of CTLA-4 and other variants in unraveling the pathogenic mechanisms of T1D in different populations and in understanding their relationships with the development of other T1D-related autoimmune diseases.