The genetic polymorphisms at the promoter region of HLA-DQB1 gene, creating responsive elements for NF1/CTF and converting the TFII-D binding site to GR-alpha

Document Type : Original article

Author

Department of Biology, College of Education Sciences, Kunduz University, Kunduz, Afghanistan

Abstract

Human leukocyte antigen-DQB1 (HLA-DQB1, OMIM: 604305) is the human major histocompatibility complex (MHC) system. HLA genes are classified into three classes (I, II, and III). The HLA-DQB1 belongs to class II, is mainly involved in the actions of the human immune system and plays a fundamental role in donor-recipient matching in transplantation and can be associated with most autoimmune diseases. In this study, the potential influence(s) of the G-71C (rs71542466) and T-80C (rs9274529) genetic polymorphisms were investigated. These polymorphisms, located in the HLA-DQB1 promoter region, have a significant frequency in the world population. The online software ALGGEN-PROMO.v8.3 was used in this work. The results indicate that the C allele at the -71 position actually creates a new potential binding site for NF1/CTF and the C allele at the -80 position changes the TFII-D binding site into a GR-alpha response element. The NF1/CTF plays the role of activator and the GR-alpha is the inhibitor; thus, according to the roles of these transcription factors, it is suggested that the above-mentioned polymorphisms alter the expression levels of HLA-DQB1. Therefore, this genetic variation is associated with autoimmune diseases; however, this cannot be generalized because this is the first report and more studies are needed in the future.

Keywords

References

  1. Gough SCL,   Simmonds MJ. The HLA region and autoimmune disease: Associations and mechanisms of Action. Curr Genomics 2007;8:453-465.
  2. Trabace S. HLA and disease association. J Headache Pain 2000;1:109-113.
  3. Saadat M. Chromosomal distribution of schizophrenia susceptibility loci. J Mol Neurosci 2013;51:401-402.
  4. Saadat M. Distributions of susceptibility loci to late onset Alzheimer's disease on human chromosomes. EXCLI J 2016;15:403-405.
  5. Mahjoub G, Saadat M. Non-random distribution of gastric cancer susceptible loci on human chromosomes. EXCLI J 2018;17:802-807. 
  6. Saadat M. Distribution of preeclampsia-related genes on human chromosomes. Taiwan J Obstet Gynecol 2022;61:909-910. 
  7. Tambur AR, Kosmoliaptsis V, Claas FHJ, Mannon RB, Nickerson P, Naesens M. Significance of HLA-DQ in kidney transplantation: time to reevaluate human leukocyte antigen– matching priorities to improve transplant outcomes? An expert review and recommendations. Kidney Int 2021;100:1012-1022.
  8. Fiorillo MT, Paladini F, Tedeschi V, Sorrentino R. HLA class I or class II and disease association: Catch the difference if you can. Front Immunol 2017;8:1475.
  9. Malavige GN, Rostron T, Rohanachandra LT, Jayaratne SD, Fernando N, Silva AD, Liyanage M, Ogg G. HLA class I and class II associations in dengue viral infections in a Sri Lankan population. PLoS One 2011;6:e20251.
  10. Arshad M, Jalil I, Raza A , Malik S, Dasti J. Novel polymorphism in the promoter region of HLA-DQB1 is a predictor of anti-HCV therapy response. Jundishapur J Microbiol 2019; 12:1-10.
  11. Naderi M, Hosseini SM, Behnampour N, Shahramian I, Moradi A. Association of HLADQ-B1 polymorphisms in three generations of chronic hepatitis B patients. Virus Res 2023;325:199036.
  12. Hillary RP, Ollilaa HM, Lin L, Desestret V, Rogemond V, Picard G, Small M, Arnulf I, Dauvilliers Y, Honnorat J, Mignot E. Complex HLA association in paraneoplastic cerebellar ataxia with anti-Yo antibodies. J Neuroimmunol 2018;315:28-32.
  13. Jia Xi, Horinouchi  T, Hitomi Y, Shono A, Soon-Khor S, Omae Y, Kojima K, kawai Y, Nagasaki M, Kaku Y, Okamoto T, Ohwada Y, Ohta K, Okuda Y, Fujimaru R, Hatae K, Kumagai N, Sawanobori E, Nakazato H, Ohtsuka Y, Nakanishi K, Shima Y, Tanaka R, Ashida A, Kamei K, Ishikura K, Nozu K, Tokunaga K, Iijima K. Strong association of the HLA-DR/DQ Locus with childhood steroid-sensitive nephrotic syndrome in the Japanese population. J Am Soc Nephrol 2018;29:2189-2199.
  14. Saify K. Genetic polymorphisms in the promoter region of catalase gene, creates new potential PAX-6 and STAT4 response elements. Mol Biol Res Commun. 2016;5: 97-100.
  15. Gronostajski RM. Roles of the NFI/CTF gene family in transcription and development. Gene 2000;249(1-2):31-45.
  16. Romanovskaya EV,  Vikhnina MV,  Grishina TV,  Ivanov MP, Leonova LE, Tsvetkova EV. Transcription factors of the NF1 family: Possible mechanisms of inducible gene expression in the evolutionary lineage of multicellular animals. J Evol Biochem Physiol 2017;53:85-92.
  17. Barnes PJ. Glucocorticosteroids: current and future directions. Br J Pharmacol 2011;163:29-43.
  18. Celada A, McKercher S, Maki RA. Repression of major histocompatibility complex IA expression by glucocorticoids: the glucocorticoid receptor inhibits the DNA binding of the X box DNA binding protein. J Exp Med 1993;177:691-698.
  19. Petta I, Dejager L, Ballegeer M, Lievens S, Tavernier J, Bosscher K, Libert C. The interactome of the glucocorticoid receptor and its influence on the actions of glucocorticoids in combatting inflammatory and infectious diseases. Microbiol Mol Biol Rev 2016;80:495-522.
  20. Louder RK, He Y, López-Blanco JR, Fang J, Chacon P, Nogales E. Structure of promoter-bound TFIID and insight into human PIC assembly. Nature 2016;531(7596): 604-609.
  21. Saify K, Saadat I, Saadat M. Influence of A-21T and C-262T genetic polymorphisms at the promoter region of the catalase (CAT) on gene expression. Environ Health Prev Med 2016; 21:382-386.

Files

Share

How to cite

Statistics