HLA-G 5′URR regulatory polymorphisms are associated with the risk of developing gliomas

Abstract

Background

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 HLA-G 5′URR variants, sHLA-G level and clinical variables in glioma patients.

Methods

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 HLA-G 5′URR polymorphisms were typed by direct sequencing and the plasma level of sHLA-G assessed by ELISA.

Results

Haploblock within HLA-G 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 (p < 0.05). No correlation of HLA-G 5′URR variants with sHLA-G plasma level was found. Analysis of HLA-G 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 (p = 0.04).

Conclusion

Our results suggest genetic association of HLA-G 5′URR variants with risk of developing gliomas and possible contribution of HLA-G to disease pathology.

Acknowledgements

Our acknowledgements go to all the patients contributing to this study.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The study was financially supported by nonprofit organization Slovak League against Cancer in 2018 and Comenius University Grant [299/2019].