Laboratory of Medical Biology and Genetics, Faculty of Medicine, School of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.
First Propedeutic Department of Surgery, AHEPA University Hospital, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.
Int J Mol Sci. 2024 Jun 28;25(13):7161. doi: 10.3390/ijms25137161.
Papillary thyroid cancer (PTC) is the most common type of thyroid malignancy with an increased female incidence ratio. The specific traits of X chromosome inheritance may be implicated in gender differences of PTC predisposition. The aim of this study was to investigate the association of two X-linked genes, Forkhead Box P3 () and Protein Phosphatase 1 Regulatory Subunit 3F (), with PTC predisposition and gender disparity. One hundred thirty-six patients with PTC and an equal number of matched healthy volunteers were enrolled in the study. Genotyping for rs3761548 () and rs5953283 () was performed using polymerase chain reaction-restriction fragment length polymorphism assay (PCR-RFLP). The methylation status of was assessed using the combined bisulfite restriction analysis (COBRA) method. The SPSS software was used for statistical analyses. Gender stratification analysis revealed that the CA and AA genotypes and the A allele of rs3761548 variant are associated with PTC predisposition only in females. Moreover, different methylation status was observed up to the promoter locus of between PTC female patients, carrying the CA and CC genotype, and controls. Both revealed associations may explain the higher PTC incidence in females through reducing FOXP3 expression as reported in immune related blood cells.
甲状腺癌（PTC）是最常见的甲状腺恶性肿瘤，女性发病率较高。X 染色体遗传的特定特征可能与 PTC 易感性的性别差异有关。本研究旨在探讨两个 X 连锁基因叉头框蛋白 P3（FOXP3）和蛋白磷酸酶 1 调节亚基 3F（PPP1R3F）与 PTC 易感性和性别差异的关系。本研究纳入了 136 例 PTC 患者和等量的匹配健康志愿者。采用聚合酶链反应-限制性片段长度多态性分析（PCR-RFLP）方法对 rs3761548（）和 rs5953283（）进行基因分型。采用联合亚硫酸氢盐限制性分析（COBRA）方法评估的甲基化状态。采用 SPSS 软件进行统计分析。性别分层分析显示，rs3761548 变异的 CA 和 AA 基因型和 A 等位基因仅与女性的 PTC 易感性相关。此外，在携带 CA 和 CC 基因型的 PTC 女性患者和对照者的启动子位点观察到的不同甲基化状态之间存在差异。已有研究表明，这两种关联可能通过降低免疫相关血细胞中的 FOXP3 表达来解释女性中更高的 PTC 发病率。
