Cytotoxic T-lymphocyte associated antigen 4 polymorphism and Hashimoto’s thyroiditis susceptibility: a meta-analysis

Abstract

The association between cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) exon-1 +49 A/G polymorphism and Hashimoto's thyroiditis (HT) has been widely studied. The results, however, are mixed. This study provides a comprehensive evaluation of the relationship between the genetic risks of CTLA-4 +49 A/G polymorphism and HT. A meta-analysis was conducted in over 4,600 subjects included in 18 case-control studies that were published up to November 15th, 2012. Our meta-analysis indicated that the CTLA-4 genotype was associated with the risk of HT in the allele comparison, homozygote comparison, heterozygote comparison, the dominant genetic model and the recessive genetic model. In the dominant genetic model, variant G allele carriers (GG + GA) of CTLA-4 +49 A/G polymorphism increased the risk of HT comparing to the homozygote AA [odds ratio (OR) = 1.70, 95% confidence interval (CI) 1.37-2.12 for GG + AG vs. AA]. The analysis by ethnicity groups suggested that Asian population (OR = 2.13, 95% CI 1.48-3.07 for GG + AG vs. AA) and Caucasian population (OR = 1.47, 95% CI 1.13-1.91 for GG + AG vs. AA) had significant increased HT risks. The association remained significant after adjusting for publication bias using the trim and fill method. Sensitivity analysis showed that the results were less stable, suggesting that these results should be explained with caution. In summary, this meta-analysis suggested that CTLA-4 +49 A/G polymorphism may be a risk factor for HT.

Association of CTLA-4 gene polymorphisms −318C/T and +49A/G and Hashimoto's thyroidits in Zahedan, Iran

“…The G allele has been associated with the reduction of T-cell proliferation (23). A meta-analysis study published in 2014 revealed that the CTLA-4 gene was associated with the risk of HT, and G allele carriers (GG + GA) of this polymorphism, considered as the dominant genetic model, were associated with an increased the risk of HT (24). However, in another meta-analysis study, this association was not identified (25).…”

Association of Cytotoxic T-Lymphocyte-Associated Protein 4 (CTLA4) Gene Polymorphisms with Autoimmune Thyroid Disease in Children and Adults: Case-Control Study

“…These two polymorphisms are associated with thyroid antibody production [ 27 , 28 ], GD relapse [ 25 ], Graves ophthalmopathy [ 29 , 30 ], and susceptibility to GD [ 23 , 31 ] and HD [ 32 , 33 ]. Recently, many meta-analyses have also demonstrated the association between CTLA4 polymorphisms and AITD [ 34 – 38 ]. However, studies on GD in pediatric populations are limited and inconsistent [ 39 – 41 ].…”

Molecular-genetic mechanisms in development of degree of function and hyperplasia of thyroid gland of patients with nodular goiter with autoimmune thyroiditis and thyroid adenoma

“…However, several immunological alterations have been found in these patients, such as HLA-DR antigen expression in thyrocytes, the presence of growth-stimulating immunoglobulins, and an increase in dendritic cells and lymphocytes, which suggest the possibility of autoimmune problems (1,(8)(9)(10). Although many of these findings may be an epiphenomenon of other primary defects in immunoregulation, the alteration of lymphocyte populations indicates a primary defect (6,7,10,(12)(13)(14)(15)(16)(17)(18). Variations in several genes have been studied as possible risk factors for Hashimoto thyroiditis.…”

“…Other genes that have been associated with AIT help regulate the immune system or are involved in normal thyroid function. Most of the genetic variations that have been discovered are thought to have a small impact on a person's overall risk of developing this condition (14)(15)(16)(17)(18).…”

“…AIT thought to result from a combination of genetic and environmental factors (1)(2)(3)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). Some of these factors have been identified, but many remain unknown (19)(20)(21)(22)(23)(24).…”