The International Journal of Romanian Society of Endocrinology / Registered in 1938

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July - September 2022, Volume 18, Issue 3
Endocrine Care

Jiang X, Hu H, Fu Z, Su Y, Long J

Association between the CTLA-4 EXON 1+49A/G Polymorphism and the Relapse of Grave’s Disease after ATD Withdrawal: A Meta-Analysis

Acta Endo (Buc) 2022, 18 (3): 324-332
doi: 10.4183/aeb.2022.324

Background. The cytotoxic T lymphocyteassociated molecules-4 (CTLA-4) is related to the relapse of Graves’ disease (GD) after anti-thyroid drugs (ATDs) withdrawal. We performed a meta-analysis to generate large-scale evidence on whether the CTLA-4 exon 1+49A/G polymorphism can predict the relapse of GD after ATDs withdrawal. Methods and Results. The PubMed, EMBASE,the Cochrane Library and reference lists of relevant studies were searched to identify eligible studies from inception to Jan, 2021. Ten eligible studies consisting of 1450 GD patients with a total of 848 relapsed patients were included in the meta-analysis. In Caucasians patients, the CTLA-4 exon 1+49A/G polymorphism significantly elevated the relapse risk of GD in additive (OR = 2.07, 95% CI: 1.18-3.62, P=0.011), dominant (OR = 2.52, 95% CI: 1.17-5.41, P=0.02), homozygote model(OR = 3.264, 95% CI: 1.25-8.52, P=0.016), except recessive (OR = 2.18, 95% CI = 0.98-4.86, P = 0.062) and heterozygote model (OR = 2.141, 95% CI = 0.958-4.786, P = 0.064). In Asian subgroup, none of these genotypes show any associations with the relapse of GD after ATDs withdrawal. Conclusion. This meta-analysis suggests that the CTLA-4 exon1 +49A/G polymorphism is associated with the relapse risk of GD after ATDs withdrawal in Caucasians, not Asians. Compared with the AA genotype, Caucasian patients with GG genotype have 3.264 times risk of relapse. A more aggressive treatment such as radioactive iodine or thyroidectomy, or longer periods treatment of ATDs should be recommended in Caucasian patients with the GG genotype.

Keywords: Graves’ disease, anti-thyroid drugs, relapse, CTLA-4.

Correspondence: Jian Long, The First Affiliated Hospital of Chongqing Medical University, Department of Endocrinology, Chongqing, China,