Association of CD40 and thyroglobulin genes with later-onset Graves' disease in Taiwanese patients

Abstract

Objective: Graves' disease (GD) is known to be associated with thyroglobulin (TG) and CD40 genes. Therefore, we decided to investigate the relationship of age at onset of GD with CD40 and TG gene susceptibilities in a Taiwanese population. Design and method: We analyzed the association of TG and CD40 polymorphisms with age at onset of GD in Taiwanese patients. We stratified patients into those with early onset (!40 years; 30.3G4.8 years; nZ135) and later onset (R40 years; 52.3G6.3 years; nZ80) and compared the results with those of 141 normal controls. Results: We found a significant statistical difference in the T/T genotype frequency of E33 single nucleotide polymorphism (SNP) and G/G genotype frequency of E12 SNP when compared with the control group (P!0.001). In addition, the frequencies of the T allele and TT genotype of the CD40 SNP were found to be significantly increased in GD patients who developed GD aged over 40 years than those below 40 years (allele: c 2 Z5.299, PZ0.021, ORZ1.597; genotype: c 2 Z6.168, PZ0.046). By contrast, the frequencies of genotypes in the TG gene E10, E12, and E33 SNPs were not found to be significantly different in GD patients who developed GD when aged over 40 years when compared with those aged below 40 years. Conclusions: These data suggest that the T/T genotype and T allele in the CD40 gene are more likely to be associated with late-onset GD in Taiwanese patients.European Journal of Endocrinology 159 617-621

Immunogenetics of autoimmune thyroid diseases: A comprehensive review

“…Indeed the T allele and TT genotype were found to carry a protective effect and even linked to later-age onset of GD. [60, 61]. In animal models of GD, blockade of CD40 stimulation has suppressed the progression to murine thyroiditis [53, 62, 63].…”

Analysis of thyroglobulin gene polymorphisms in patients with autoimmune thyroiditis

“…There are several polymorphisms distributed throughout the TG gene. Some of them have been associated with AITD [32][33][34][35][36][37][38][39] and experimental autoimmune thyroiditis in different strains of mice [35].…”

The replication of the association of the rs6832151 within chromosomal band 4p14 with Graves' disease in a Polish Caucasian population

“…CHRNA9 encodes nicotinic acetylcholine receptor alpha 9 (nAChRα9) and is expressed among others in mice B lymphocytes subtypes but its function is not clearly understood (12). It has been shown that nAChR α9α10 are coupled to CD40 (12) encoded by a gene previously implicated as a susceptibility locus to GD (13)(14)(15)(16)(17)(18). While CHRNA9 can potentially be involved in GD pathogenesis, on the basis of the positional mapping data as well as the relatively high expression in CD4 and CD8 T cells Chan et al tentatively proposed GDCG4p14 as a the primary diseases-associated locus (2).…”