Institute of Immunology, Faculty of Medicine, Comenius University in Bratislava, Bratislava, Slovakia.
Institute of Medical Physics, Biophysics, Informatics and Telemedicine, Faculty of Medicine, Comenius University in Bratislava, Bratislava, Slovakia.
Int J Neurosci. 2023 Apr;133(4):365-374. doi: 10.1080/00207454.2021.1922401. Epub 2021 Sep 28.
Human leukocyte antigen G (HLA-G) belongs to non-classical MHC class I molecules that is involved in the suppression of immune response. As HLA-G plays important role in the maintenance of fetal tolerance, its overexpression has been associated with tumor progression. For the regulation of HLA-G levels, genetic variants within the 5' upstream regulatory region (5'URR) are of crucial importance. Our study aimed to analyze the association between 16 5'URR variants, sHLA-G level and clinical variables in glioma patients.
We investigated 59 patients with gliomas (mean age 54.70 ± 15.10 years) and 131 healthy controls (mean age 41.45 ± 9.75 years). Patient's blood was obtained on the day of surgical treatment. The 5'URR polymorphisms were typed by direct sequencing and the plasma level of sHLA-G assessed by ELISA.
Haploblock within 5'URR consisting of -762T, -716G, -689G, -666T, -633A, followed by -486C and -201A alleles were significantly more frequent in patients with gliomas than in the controls ( < 0.05). No correlation of 5'URR variants with sHLA-G plasma level was found. Analysis of 5'URR variants with main clinical variables in patients with grade IV gliomas revealed that haploblock carriers of -762CT, -716TG, -689AG, -666GT, -633GA, -486AC, -477GC, -201GA followed by -369AC carriers tend to have lower age at onset as compared to other genotype carriers ( = 0.04).
Our results suggest genetic association of 5'URR variants with risk of developing gliomas and possible contribution of HLA-G to disease pathology.
人类白细胞抗原 G（HLA-G）属于非经典 MHC I 类分子，参与免疫反应的抑制。由于 HLA-G 在维持胎儿耐受中起重要作用，其过度表达与肿瘤进展有关。为了调节 HLA-G 水平，5'上游调控区（5'URR）内的遗传变异至关重要。我们的研究旨在分析 16 个 5'URR 变异、sHLA-G 水平与胶质瘤患者临床变量之间的关系。
我们研究了 59 名胶质瘤患者（平均年龄 54.70±15.10 岁）和 131 名健康对照者（平均年龄 41.45±9.75 岁）。患者的血液在手术当天采集。通过直接测序分析 5'URR 多态性，通过 ELISA 评估 sHLA-G 血浆水平。
5'URR 内的单倍型块由-762T、-716G、-689G、-666T、-633A 组成，随后是-486C 和-201A 等位基因，在胶质瘤患者中比在对照组中更为常见（<0.05）。未发现 5'URR 变异与 sHLA-G 血浆水平相关。对 4 级胶质瘤患者的主要临床变量进行 5'URR 变异分析表明，-762CT、-716TG、-689AG、-666GT、-633GA、-486AC、-477GC、-201GA 单倍型携带者，随后是-369AC 携带者，发病年龄较低，与其他基因型携带者相比（=0.04）。
我们的结果表明，5'URR 变异与胶质瘤发病风险存在遗传关联，HLA-G 可能对疾病病理学有贡献。
