Cytotoxic T Lymphocyte-Associated Antigen 4 Gene Polymorphisms and Autoimmune Thyroid Diseases: An Updated Systematic Review and Cumulative Meta-Analysis

Abstract

The association of the cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) gene and susceptibility to autoimmune thyroid diseases (AITDs) has been studied extensively. However, the results were not the same in different ethnic groups. We updated the meta-analysis of association of CTLA-4 gene polymorphisms with AITDs and summarized the results in specific ethnicity. The associations of A49G gene polymorphism with GD, A49G gene polymorphism with HT, CT60 gene polymorphism with GD, and CT60 gene polymorphism with HT were summarized based on the literatures published up to October 30, 2014, in English or Chinese languages. The participants involved in the studies of A49G with GD, A49G with HT, CT60 with GD, and CT60HT were 39004 subjects (in 51 studies), 13102 subjects (in 22 studies), 31446 subjects (in 22 studies), and 6948 subjects (in 8 studies), respectively. The pooled ORs of CTLA-4 gene polymorphisms with AITDs were larger than 1.00, and the 95% CIs of ORs were statistically significant among whole population analyses. However, the subgroup analysis demonstrated that pooled ORs of A49G polymorphisms with GD among Africans or Americans are less than 1.00. The accumulated evidence suggests that the G allele mutant of A49G and CT60 increased the risks of HT and GD.

CTLA-4 as a genetic determinant in autoimmune Addison’s disease

“…However, we have tested the Norwegian cohort in this study and in a pilot subgroup of British AAD patients for autoantibodies against 21-OH, a positive marker for an ongoing autoimmune condition against the adrenals, and found similar results (data not shown). Deviations of results in different populations have also been reported for CTLA-4 associations with, for example, type 1 diabetes and autoimmune thyroid diseases (reviewed in Hou et al 29 and Wang et al 30 ). Notably, however, when the data indicate an association, it is most often with the same allele (for example, the G-allele concerning rs231775).…”

Autoimmune thyroid disease and type 1 diabetes mellitus: same pathogenesis; new perspective?

“… 115 – 120 CTLA-4 and its gene polymorphisms are reported to be important genetic determinants of the risk of T1DM and/or AITD. 43 , 96 , 121 – 134 …”

Is the Genetic Background of Co-Stimulatory CD28/CTLA-4 Pathway the Risk Factor for Prostate Cancer?

“…Recent series of meta-analysis pointed out, that CTLA-4 locus is rather general autoimmune than disease-specific genetic risk factor, especially the exon 1 and 3'UTR located markers, while their association with diseases susceptibility depends on the ethnicity. For example, it was shown that CTLA-4c.49A>G[G] and CT60 [G] alleles are risk factors, especially in Caucasians or Asians, for: autoimmune thyroid diseases [33], autoimmune adrenal insufficiency [34], type 1 diabetes [35], rheumatoid arthritis [36] and systemic lupus erythematosus [37,38]. The only association between CTLA-4g.319C>T and autoimmune disease susceptibility was observed for SLE in Asians [38].…”