CD40 C/T-1 polymorphism plays different roles in Graves' disease and Hashimoto's thyroiditis: a meta-analysis

CD40 plays a pathogenic role in various autoimmune diseases. However, studies investigating the association between CD40 C/T-1 polymorphism and autoimmune thyroid diseases risk have reported conflicting results and their relative population effect remains unclear; therefore, a meta-analysis was conducted. The data for this meta-analysis included 14 (4214 cases and 3851 controls) and 4 studies (623 cases and 774 controls) for the association of the CD40 C/T-1 polymorphism with Graves' disease (GD) and Hashimoto's thyroiditis (HT), respectively. Results suggested significant association for CD40 C/T-1 polymorphism (odds ratio 1.267 per C allele, p = 0.000) with GD but without HT. The individuals who carried the OC or C/T genotype have significantly increased GD risk compared with those who carried T/T genotype (GC vs. T/T: OR = 1.596,95% CI, 1.256 similar to 2.028; C/T vs. T/T: OR = 1.210, 95% CI, 1.032 similar to 1.419; dominant model: OR= 1.366, 95% CI, 1.175 similar to 1.587; recessive model: OR = 1.322,95% CI, 1.147-1.523), while no association was observed in HT. When stratified by ethnicity, the significant association between polymorphism and GD risk of Caucasians was found only in recessive models; but that of Asians was found in all models. In the subgroup analysis of study design, we found thyroid antibody status should be ascertained in controls and euthyroidism subjects with higher levels of thyroid antibody should be excluded from control and included into HT to avoid bias. Our meta-analysis showed that CD40 C/T-1 polymorphism plays different roles in GD and HT. Further studies will be needed to confirm our findings.