title: CD226 rs763361 is associated with the susceptibility to type 1 diabetes and greater frequency of GAD65 autoantibody in a Brazilian cohort.
abstract: CD226 rs763361 variant increases susceptibility to type 1 diabetes (T1D) in Caucasians. There is no data about CD226 variants in the very heterogeneous Brazilian population bearing a wide degree of admixture. We investigated its association with T1D susceptibility, clinical phenotypes, and autoimmune manifestations (islet and extrapancreatic autoantibodies). Casuistry. 532 T1D patients and 594 controls in a case-control study. Initially, CD226 coding regions and boundaries were sequenced in a subset of 106 T1D patients and 102 controls. In a second step, two CD226 variants, rs763361 (exon 7) and rs727088 (3' UTR region), involved with CD226 regulation, were genotyped in the entire cohort. C-peptide and autoantibody levels were determined. No new polymorphic variant was found. The variants rs763361 and rs727088 were in strong linkage disequilibrium. The TT genotype of rs763361 was associated with TID risk (OR = 1.503;  95%  CI = 1.135-1.991; P = 0.0044), mainly in females (P = 0.0012), greater frequency of anti-GAD autoantibody (31.9% × 24.5%; OR = 1.57; CI = 1.136-2.194; P = 0.0081), and lower C-peptide levels when compared to those with TC + CC genotypes (0.41 ± 0.30 ng/dL versus 0.70 ± 0.53 ng/dL P = 0.0218). Conclusions. The rs763361 variant of CD226 gene (TT genotype) was associated with susceptibility to T1D and with the degree of aggressiveness of the disease in T1D patients from Brazil. Ancestry had no effect.
authors.affiliation: Laboratório de Carboidratos e Radioimunoensaio (LIM 18), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Avenida Dr. Arnaldo 455, 01246-903 São Paulo, SP, Brazil.
authors.forename: Teresa Cristina Colvara
authors.initials: TC
authors.lastname: Mattana
authors.affiliation: Laboratório de Carboidratos e Radioimunoensaio (LIM 18), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Avenida Dr. Arnaldo 455, 01246-903 São Paulo, SP, Brazil.
authors.forename: Aritania Sousa
authors.initials: AS
authors.lastname: Santos
authors.affiliation: Laboratório de Carboidratos e Radioimunoensaio (LIM 18), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Avenida Dr. Arnaldo 455, 01246-903 São Paulo, SP, Brazil.
authors.forename: Rosa Tsuneshiro
authors.initials: RT
authors.lastname: Fukui
authors.affiliation: Laboratório de Carboidratos e Radioimunoensaio (LIM 18), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Avenida Dr. Arnaldo 455, 01246-903 São Paulo, SP, Brazil.
authors.forename: Debora Teixeira Oliveira
authors.initials: DT
authors.lastname: Mainardi-Novo
authors.affiliation: Laboratório de Carboidratos e Radioimunoensaio (LIM 18), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Avenida Dr. Arnaldo 455, 01246-903 São Paulo, SP, Brazil.
authors.forename: Vinícius Silva
authors.initials: VS
authors.lastname: Costa
authors.affiliation: Laboratório de Carboidratos e Radioimunoensaio (LIM 18), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Avenida Dr. Arnaldo 455, 01246-903 São Paulo, SP, Brazil.
authors.forename: Rosa Ferreira
authors.initials: RF
authors.lastname: Santos
authors.affiliation: Departamento de Genética e Biologia Evolutiva, Instituto de Biociências da Universidade de São Paulo, Rua do Matão 277, 05422-970 São Paulo, SP, Brazil.
authors.forename: Sergio Russo
authors.initials: SR
authors.lastname: Matioli
authors.affiliation: Laboratório de Carboidratos e Radioimunoensaio (LIM 18), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Avenida Dr. Arnaldo 455, 01246-903 São Paulo, SP, Brazil.
authors.forename: Maria Elizabeth Rossi
authors.initials: ME
authors.lastname: da Silva
mesh_terms: D020413:3' Untranslated Regions; D000293:Adolescent; D000328:Adult; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics*; D001323:Autoantibodies / Q000737:chemistry*; D001938:Brazil; D002096:C-Peptide / Q000097:blood; D016022:Case-Control Studies; D002648:Child; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005091:Exons; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005968:Glutamate Decarboxylase / Q000235:genetics*; D006801:Humans; D008297:Male; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult; D000098862:T Lineage-Specific Activation Antigen 1
chemical_list: D020413:3' Untranslated Regions; D000945:Antigens, Differentiation, T-Lymphocyte; D001323:Autoantibodies; D002096:C-Peptide; D000098862:T Lineage-Specific Activation Antigen 1; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2