title: Association of TNF-α, CTLA4, and PTPN22 polymorphisms with type 1 diabetes and other autoimmune diseases in Brazil.
abstract: 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.
authors.affiliation: Laboratório de Imunopatologia Keiso Asami, Universidade Federal de Pernambuco, Recife, PE, Brasil.
authors.forename: N A C
authors.initials: NA
authors.lastname: Tavares
authors.affiliation: Laboratório de Imunopatologia Keiso Asami, Universidade Federal de Pernambuco, Recife, PE, Brasil.|Departamento de Genética, Universidade Federal de Pernambuco, Recife, PE, Brasil.
authors.forename: M M S
authors.initials: MM
authors.lastname: Santos
authors.affiliation: Laboratório de Imunopatologia Keiso Asami, Universidade Federal de Pernambuco, Recife, PE, Brasil.|Departamento de Genética, Universidade Federal de Pernambuco, Recife, PE, Brasil.
authors.forename: R
authors.initials: R
authors.lastname: Moura
authors.affiliation: Unidade de Endocrinologia Pediátrica do Hospital das Clínicas, Universidade Federal de Pernambuco, Recife, PE, Brasil.
authors.forename: J
authors.initials: J
authors.lastname: Araújo
authors.affiliation: Laboratório de Imunopatologia Keiso Asami, Universidade Federal de Pernambuco, Recife, PE, Brasil.|Departamento de Genética, Universidade Federal de Pernambuco, Recife, PE, Brasil.
authors.forename: R L
authors.initials: RL
authors.lastname: Guimarães
authors.affiliation: Laboratório de Imunopatologia Keiso Asami, Universidade Federal de Pernambuco, Recife, PE, Brasil.|Departamento de Genética, Universidade Federal de Pernambuco, Recife, PE, Brasil.
authors.forename: S
authors.initials: S
authors.lastname: Crovella
authors.affiliation: Laboratório de Imunopatologia Keiso Asami, Universidade Federal de Pernambuco, Recife, PE, Brasil.|Departamento de Patologia, Universidade Federal de Pernambuco, Recife, PE, Brasil.
authors.forename: L A C
authors.initials: LA
authors.lastname: Brandão
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D001938:Brazil; D060908:CTLA-4 Antigen / Q000235:genetics*; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics*; D017422:Sequence Analysis, DNA; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D055815:Young Adult
chemical_list: D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22