title: Association of CD40 gene polymorphism (C-1T) with susceptibility and phenotype of Graves' disease.
abstract: OBJECTIVE
  Recently, a functional polymorphism in the CD40 gene at position -1, C to T change (C-1T) has been identified and the C/C genotype has been reported to be associated with Graves' disease (GD).
  
  
  METHODS
  We performed a case-control, replication study on 556 patients with GD and 611 healthy subjects in a Polish population. Furthermore, we analyzed the distribution of CD40 genotypes in subgroups of patients with GD divided according to age of onset, gender, family history, tobacco smoking, ophthalmopathy, and genetic parameters (CTLA4 49G, PTPN22/LYP 1858T or HLA-DRB1*03 alleles).
  
  
  RESULTS
  Although the frequency of C/C genotype was increased in GD compared to controls, the difference was not significant (60.5% versus 55.8%, p = 0.062, odds ratio [OR] = 1.21, 95% confidence interval [CI]: 0.96-1.53). Because our study was underpowered to detect such a modest association, we performed a meta-analysis with the data from previous studies. The combined OR for the C/C genotype as a risk factor for GD was 1.22 (95% CI: 1.08-1.38, p = 0.001). We failed to find an interaction between CD40 genotypes and other GD susceptibility alleles. No significant genotype-phenotype associations were found.
  
  
  CONCLUSIONS
  Our results support the notion that CD40 C-1T polymorphism has a modest effect on genetic susceptibility to sporadic GD.
authors.affiliation: Department of Endocrinology, Medical Research Center, Polish Academy of Science, Warsaw, Poland.
authors.forename: Alina
authors.initials: A
authors.lastname: Kurylowicz
authors.forename: Dorota
authors.initials: D
authors.lastname: Kula
authors.forename: Rafal
authors.initials: R
authors.lastname: Ploski
authors.forename: Agata
authors.initials: A
authors.lastname: Skorka
authors.forename: Beata
authors.initials: B
authors.lastname: Jurecka-Lubieniecka
authors.forename: Jadwiga
authors.initials: J
authors.lastname: Zebracka
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Steinhof-Radwanska
authors.forename: Kornelia
authors.initials: K
authors.lastname: Hasse-Lazar
authors.forename: Yuji
authors.initials: Y
authors.lastname: Hiromatsu
authors.forename: Barbara
authors.initials: B
authors.lastname: Jarzab
authors.forename: Tomasz
authors.initials: T
authors.lastname: Bednarczuk
mesh_terms: D000328:Adult; D019013:CD40 Antigens / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006111:Graves Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D010641:Phenotype; D011044:Poland; D020641:Polymorphism, Single Nucleotide
chemical_list: D019013:CD40 Antigens