title: The promoter region of the CTLA4 gene is associated with type 1 diabetes mellitus.
abstract: The CTLA4 (cytotoxic T lymphocyte associated antigen-4) gene encodes the T cell receptor involved in the control of T cell proliferation and mediates T cell apoptosis. C-T polymorphism is present at position -318 from the ATG start codon in the promoter region of the gene. We report a study on the polymorphism in 347 unrelated children with type 1 diabetes mellitus (DM) (age at diagnosis 7.2+/-3.8 years) and their 260 healthy siblings as controls. Genotype C/C conferred a risk of type 1 DM (RR = 2.02, 95% CI 1.32-3.10, pc = 0.0033). The gene frequency of the C allele was higher in patients (RR = 1.91, 95% CI 1.28-2.84, pc = 0.0026). The gene frequency and phenotype frequency of the T allele were negatively associated with type 1 DM (RR = 0.52, 95% CI 0.35-0.78, pc = 0.0026 and RR = 0.49, 95% CI 0.32-0.76, pc = 0.0022, respectively). The frequency of genotype C/T was lower in patients (RR = 0.50, 95% CI 0.32-0.78, pc = 0.0051). This study demonstrates that nucleotide -318 C-T polymorphism of the CTLA4 gene is associated with type 1 DM. The promoter allele -318 C confers a risk of type 1 DM but allele -318 T confers protection against this disease.
authors.affiliation: Department of Pediatrics, Medical Research, Mackay Memorial Hospital, Taipei, Taiwan. yannlee@ms2.mmh.org.tw
authors.forename: Y J
authors.initials: YJ
authors.lastname: Lee
authors.forename: F S
authors.initials: FS
authors.lastname: Lo
authors.forename: S G
authors.initials: SG
authors.lastname: Shu
authors.forename: C H
authors.initials: CH
authors.lastname: Wang
authors.forename: C Y
authors.initials: CY
authors.lastname: Huang
authors.forename: H F
authors.initials: HF
authors.lastname: Liu
authors.forename: C C
authors.initials: CC
authors.lastname: Wu
authors.forename: T Y
authors.initials: TY
authors.lastname: Yang
authors.forename: J G
authors.initials: JG
authors.lastname: Chang
mesh_terms: D000069594:Abatacept; D000293:Adolescent; D000483:Alleles; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics*; D060908:CTLA-4 Antigen; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D018796:Immunoconjugates; D007223:Infant; D008297:Male; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011401:Promoter Regions, Genetic
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D018796:Immunoconjugates; D000069594:Abatacept