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  • Title: Association between CTLA-4 + 49A > G and - 318C > T single-nucleotide polymorphisms and susceptibility to thyroid neoplasm.
    Author: Abtahi S, Izadi Jahromi F, Dabbaghmanesh MH, Malekzadeh M, Ghaderi A.
    Journal: Endocrine; 2018 Oct; 62(1):159-165. PubMed ID: 30078171.
    Abstract:
    PURPOSE: Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4 or CD152) is among the immune checkpoint molecules and its abnormal expression in cancer predisposed individuals might make the person more susceptible to tumor initiation and progression. Considering the implication of single-nucleotide polymorphisms (SNPs) in CTLA-4 gene expression and probably protein function, one can assume the involvement of these SNPs in neoplastic diseases. rs5742909 ( - 318C > T) and rs231775 ( + 49 A > G) are among the most commonly studied SNPs and have been considered as genetic factors related to thyroid diseases. In this cross-sectional study, we aimed to elucidate the association between these SNPs and susceptibility to various types of thyroid cancers. METHODS: We investigated the genetic polymorphisms of - 318C > T and + 49 A > G in the CTLA-4 gene by means of ARMS-PCR and RFLP-PCR, respectively, in 167 patients with thyroid carcinomas (papillary, follicular, and anaplastic). The results were then compared with a group of 100 age-sex matched healthy individuals. RESULTS: A statistically significant association was observed between the presence of G allele in + 49 A > G locus and thyroid carcinoma, when comparing cases and controls (OR = 2.10; 95% CI = 1.35-3.28; P = 0.001) and the frequency of heterozygotes (AG) was higher than homozygotes for allele A (AA), in patients with and papillary thyroid carcinoma (PTC). Regarding Hashimoto's thyroiditis, the frequencies of A allele and AA genotype in PTC patients were higher than Hashimoto patients with no history of cancer (OR = 4.67, 95% CI = 2.70-8.08, P < 0.0001; and, OR = 4.68, 95% CI = 1.84-11.91, P = 0.0012; respectively). However; we observed no difference among allele/genotype frequencies in regards to locus - 318C > T. CONCLUSION: In this study, we observed that G allele in + 49 A > G and possibly lower expression of mutated CTLA-4 molecule, is associated with higher susceptibility to thyroid carcinoma. Although the G allele frequency was higher in thyroid cancer patients, when justified for the presence of lymphocytic thyroiditis, the presence of A allele seemed to increase the odds for PTC in patients with Hashimoto's disease.
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