ECE2007 Oral Communications Thyroid clinical (7 abstracts)
Background: CTLA-4 polymorphisms have been widely examined for their associations with autoimmune thyroid diseases (Graves disease [GD] and Hashimoto thyroiditis [HT]) but their relative population effect remains unclear.
Methodology/Principal findings: Meta-analyses of group-level data from 32 (n=11.019 subjects) and 12 (n=4.479) published and unpublished studies were performed for the association of the A49G polymorphism with GD and HT, respectively. Fifteen (n=7.246) and 6 (n=3.086) studies were available for the CT60 polymorphism, respectively. Meta-analyses of individual-level data from 10 (n=4.906 subjects) and 5 (n=2.386) collaborating teams for GD and HT, respectively, using haplotypes of both polymorphisms were also performed. Group-level data suggested significant associations with GD and HT for both A49G (odds ratio 1.49, P=6×10−14 and 1.29 [P=0.001] per G allele, respectively) and CT60 (OR 1.45, [P=2×10−9] and 1.64 [P=0.003] per G allele, respectively). Results were consistent between Asian and Caucasian descent subjects. Individual-level data showed that compared with the AA haplotype the risk conferred by the GG haplotype was 1.49 (95% CI: 1.311.70) and 1.36 (95% CI: 1.161.59) for GD and HT, respectively. The AG haplotype also increased the risk of GD (1.35, 95% CI: 1.161.55) but not of HT (1.02, 95% CI: 0.711.47). The results for the GA haplotype were inconclusive. Data were consistent with a dose-response effect for the G-allele of CT60.
Conclusions/Interpretation: The CT60 polymorphism of CTLA-4 maps an important genetic determinant for the risk of both GD and HT across diverse populations.