Association of CD40 gene polymorphism (C-1T) with susceptibility and phenotype of Graves' disease.
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.
Kurylowicz
Alina
A
Department of Endocrinology, Medical Research Center, Polish Academy of Science, Warsaw, Poland.
Kula
Dorota
D
Ploski
Rafal
R
Skorka
Agata
A
Jurecka-Lubieniecka
Beata
B
Zebracka
Jadwiga
J
Steinhof-Radwanska
Katarzyna
K
Hasse-Lazar
Kornelia
K
Hiromatsu
Yuji
Y
Jarzab
Barbara
B
Bednarczuk
Tomasz
T
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
D019013:CD40 Antigens