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Associations Between Three CTLA-4 Polymorphisms and Hashimoto's Thyroiditis Risk: An Updated Meta-Analysis with Trial
Yifang Hu1, Kuanfeng Xu1, Lin Jiang1
1Department of Endocrinology, The First Affiliated Hospital of Nanjing Medical University , Nanjing, China .
Genetic Testing and Molecular Biomarkers
|February 21, 2018
Summary
This study found that CTLA-4 gene variations, specifically +49A/G and CT60 single nucleotide polymorphisms (SNPs), are linked to an increased risk of Hashimoto's thyroiditis (HT). The -318C/T SNP showed no significant association, and the +49A/G SNP is a credible biomarker for HT.
Area of Science:
- Genetics
- Immunology
- Endocrinology
Background:
- Hashimoto's thyroiditis (HT) is an autoimmune disease affecting the thyroid gland.
- The CTLA-4 gene plays a crucial role in immune system regulation.
- Single nucleotide polymorphisms (SNPs) in the CTLA-4 gene are investigated for their potential association with HT susceptibility.
Purpose of the Study:
- To conduct an updated meta-analysis with trial sequential analysis (TSA) to clarify the associations between three common CTLA-4 gene SNPs (+49A/G, CT60, -318C/T) and Hashimoto's thyroiditis (HT).
- To evaluate the robustness and credibility of the observed associations using TSA.
Main Methods:
- A meta-analysis of 29 independent studies involving 3614 cases and 8839 controls was performed.
- Statistical association analyses utilized four genetic models (allelic, codominant, dominant, recessive).
- Trial sequential analysis (TSA) and the Newcastle-Ottawa Scale were employed for evidence assessment and quality evaluation.
Main Results:
- Significant associations were found between the +49A/G polymorphism and increased HT risk across all genetic models, with robust evidence confirmed by TSA.
- Subgroup analyses indicated a higher HT risk associated with +49A/G in Asians compared to Caucasians, and in adults versus pediatric populations.
- A significant association was observed for the CT60 polymorphism, particularly in the Asian subgroup, while the -318C/T polymorphism showed no significant link to HT risk.
Conclusions:
- The CTLA-4 +49A/G polymorphism is significantly associated with HT risk and can be considered a potential biomarker.
- The CTLA-4 CT60 polymorphism is also associated with HT risk, especially in Asian populations.
- The -318C/T polymorphism did not show a significant association, and further studies are needed to confirm findings for CT60 and -318C/T SNPs.