Molecular Study of IL-7R Gene Polymorphism and their Associations with Male Multiple Sclerosis Patients in Erbil Province.

Authors

  • Shukur W. Smail Department of Biology, College of Science, Salahaddin University-Erbil, Kurdistan Region, Iraq

DOI:

https://doi.org/10.21271/ZJPAS.33.1.3

Keywords:

Multiple Sclerosis, Interleukin 7 Receptor, Polymorphism, Relapsing-Remitting Multiple Sclerosis

Abstract

Multiple sclerosis (MS) is an autoimmune disease in which immune cells attacks the body cells mistakenly; it is characterized by chronic inflammation that leads to demyelination and conduction of nerve impulse is affected negatively. The cause of the disease is unknown, but it may be partially under the control of genetics, including interleukin 7 receptor alpha (IL7Rα). In this case-control study, 40 relapsing-remitting MS (RRMS) male patients, which fulfills McDonald criteria and 40 healthy controls, with matched sex, were compared depending on the rs6897932 polymorphism within the exon 6 of IL7Rα gene by Tetra-amplification refractory mutation system polymerase chain reaction (Tetra-ARMS-PCR) method. The frequency of T allele of IL7Rα rs6897932 was considerably higher in male MS patients than healthy control males (31.25 vs 17.5%). Genotype distributions of the single nucleotide polymorphism (SNP) rs6897932 deviated from Hardy-Weinberg equilibrium with a p-value of 0.80. Both homozygous (TT) and Heterozygous (CT) were non-significantly positively associated with MS male patients (OR = 6.75, 95%CI = 0.73-62.4, p = 0.059, OR = 1.68, 95%CI = 0.64-4.38, p = 0.28) respectively. The distribution of the rs6897932 polymorphism is not significantly different in our case/control study in the Erbil province.

References

AKKAD, D., HOFFJAN, S., PETRASCH-PARWEZ, E., BEYGO, J., GOLD, R. & EPPLEN, J. 2009. Variation in the IL7RA and IL2RA genes in German multiple sclerosis patients. Journal of autoimmunity, 32, 110-115.

ALCINA, A., FEDETZ, M., NDAGIRE, D., FERNÁNDEZ, O., LEYVA, L., GUERRERO, M., ARNAL, C., DELGADO, C. & MATESANZ, F. 2008. The T244I variant of the interleukin-7 receptor-alpha gene and multiple sclerosis. Tissue Antigens, 72, 158-61.

ALCINA, A., FERNÁNDEZ, Ó., GONZALEZ, J. R., CATALÁ-RABASA, A., FEDETZ, M., NDAGIRE, D., LEYVA, L., GUERRERO, M., ARNAL, C. & DELGADO, C. 2010. Tag-SNP analysis of the GFI1-EVI5-RPL5-FAM69 risk locus for multiple sclerosis. European journal of human genetics, 18, 827-831.

ASCHERIO, A. & MUNGER, K. L. 2016. Epidemiology of Multiple Sclerosis: From Risk Factors to Prevention-An Update. Seminars in Neurology, 36, 103-14.

BOOTH, D., ARTHUR, A., TEUTSCH, S., BYE, C., RUBIO, J., ARMATI, P., POLLARD, J., HEARD, R., STEWART, G. & CONSORTIUM, S. M. G. 2005. Gene expression and genotyping studies implicate the interleukin 7 receptor in the pathogenesis of primary progressive multiple sclerosis. Journal of molecular medicine, 83, 822-830.

BROWN, T. A. 2016. Gene cloning and DNA analysis: an introduction. New York, United States: John Wiley & Sons.

ČIERNY, D., HÁNYŠOVÁ, S., MICHALIK, J., KANTOROVÁ, E., KURČA, E., ŠKEREŇOVÁ, M. & LEHOTSKÝ, J. 2015. Genetic variants in interleukin 7 receptor α chain (IL-7Ra) are associated with multiple sclerosis risk and disability progression in Central European Slovak population. Journal of neuroimmunology, 282, 80-84.

DYMENT, D., SADOVNICK, A. & EBERS, G. 1997. Erratum: Genetics of multiple sclerosis (Human Molecular Genetics (1997) 6 (1693-1698)). Human Molecular Genetics, 6.

FANG, L., ISOBE, N., YOSHIMURA, S., YONEKAWA, T., MATSUSHITA, T., MASAKI, K., DOI, H., OCHI, K., MIYAMOTO, K. & KAWANO, Y. 2011. Interleukin-7 receptor alpha gene polymorphism influences multiple sclerosis risk in Asians. Neurology, 76, 2125-2127.

GOLD, R., KAPPOS, L., ARNOLD, D. L., BAR-OR, A., GIOVANNONI, G., SELMAJ, K., TORNATORE, C., SWEETSER, M. T., YANG, M. & SHEIKH, S. I. 2012. Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis. New England Journal of Medicine, 367, 1098-1107.

GREGORY, S. G., SCHMIDT, S., SETH, P., OKSENBERG, J. R., HART, J., PROKOP, A., CAILLIER, S. J., BAN, M., GORIS, A. & BARCELLOS, L. F. 2007. Interleukin 7 receptor α chain (IL7R) shows allelic and functional association with multiple sclerosis. Nature genetics, 39, 1083-1091.

HAFLER, D. A. 2004. More MS news articles for April 2004. Journal of Clinical Investigation, 113, 788-794.

HENINGER, A. K., THEIL, A., WILHELM, C., PETZOLD, C., HUEBEL, N., KRETSCHMER, K., BONIFACIO, E. & MONTI, P. 2012. IL-7 abrogates suppressive activity of human CD4+CD25+FOXP3+ regulatory T cells and allows expansion of alloreactive and autoreactive T cells. Journal of Immunology, 189, 5649-58.

MAGDELDIN, S. 2012. Gel electrophoresis: Principles and basics. Deutschland: BoD–Books on Demand.

MAJDINASAB, N., HOSSEINI BEHBAHANI, M., GALEHDARI, H. & MOHAGHEGH, M. 2014b. Association of interleukin 7 receptor gene polymorphism rs6897932 with multiple sclerosis patients in Khuzestan. Iranian journal of neurology, 13, 168-171.

MANOLIO, T. A., COLLINS, F. S., COX, N. J., GOLDSTEIN, D. B., HINDORFF, L. A., HUNTER, D. J., MCCARTHY, M. I., RAMOS, E. M., CARDON, L. R. & CHAKRAVARTI, A. 2009. Finding the missing heritability of complex diseases. Nature, 461, 747-753.

O'DOHERTY, C., KANTARCI, O. & VANDENBROECK, K. 2008. IL7RA polymorphisms and susceptibility to multiple sclerosis. New England Journal of Medicine, 358, 753-754.

RIZVI, S. A., STONE, J. A., CHAUDHRY, S. T., HADDAD, N., WONG, B. & GRIMES, J. O. 2020. Clinical Decision-Making in the Management of Multiple Sclerosis. Clinical Neuroimmunology. Springer.

ROSATI, G. 2001. The prevalence of multiple sclerosis in the world: an update. Neurological sciences, 22, 117-139.

RONAGHI, M., VALLIAN, S., & ETEMADIFAR, M. (2009). CD24 gene polymorphism is associated with the disease progression and susceptibility to multiple sclerosis in the Iranian population. Psychiatry Research, 170(2-3), 271-272.

SAHAMI-FARD, M. H., MOZHDEH, M., IZADPANAH, F., KASHANI, H. H. & NEZHADI, A. 2020. Interleukin 7 receptor T244I polymorphism and the multiple sclerosis susceptibility: a meta-analysis. Journal of Neuroimmunology, 577166.

SAWCER, S., HELLENTHAL, G., PIRINEN, M., SPENCER, C. C., PATSOPOULOS, N. A., MOUTSIANAS, L., DILTHEY, A., SU, Z., FREEMAN, C. & HUNT, S. E. 2011. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature, 476, 214.

TEUTSCH, S. M., BOOTH, D. R., BENNETTS, B. H., HEARD, R. N. & STEWART, G. J. 2003. Identification of 11 novel and common single nucleotide polymorphisms in the interleukin-7 receptor-α gene and their associations with multiple sclerosis. European journal of human genetics, 11, 509-515.

VALCARCEL, A. M., LINN, K. A., KHALID, F., VANDEKAR, S. N., TAUHID, S., SATTERTHWAITE, T. D., MUSCHELLI, J., BAKSHI, R. & SHINOHARA, R. T. MIMoSA: An Approach to Automatically Segment T2 Hyperintense and T1 Hypointense Lesions in Multiple Sclerosis. International MICCAI Brainlesion Workshop, 2018. New York City: Springer.

WEBER, F., FONTAINE, B., COURNU-REBEIX, I., KRONER, A., KNOP, M., LUTZ, S., MÜLLER-SARNOWSKI, F., UHR, M., BETTECKEN, T. & KOHLI, M. 2008. IL2RA and IL7RA genes confer susceptibility for multiple sclerosis in two independent European populations. Genes & Immunity, 9, 259-263.

WILKINS, A. 2018. Mechanisms of disease progression. Progressive Multiple Sclerosis. New York City: Springer.

ZHANG, Y., ZHANG, J., LIU, H., HE, F., CHEN, A., YANG, H. & PI, B. 2019. Meta-analysis of FOXP3 gene rs3761548 and rs2232365 polymorphism and multiple sclerosis susceptibility. Medicine, 98.

ZHANG, Z., DUVEFELT, K., SVENSSON, F., MASTERMAN, T., JONASDOTTIR, G., SALTER, H., EMAHAZION, T., HELLGREN, D., FALK, G. & OLSSON, T. 2005. Two genes encoding immune-regulatory molecules (LAG3 and IL7R) confer susceptibility to multiple sclerosis. Genes & Immunity, 6, 145-152.

ZUVICH, R., MCCAULEY, J., PERICAK-VANCE, M. & HAINES, J. Genetics and pathogenesis of multiple sclerosis. Seminars in immunology, 2009. Netherlands: Elsevier.

Published

2021-02-20

How to Cite

Shukur W. Smail. (2021). Molecular Study of IL-7R Gene Polymorphism and their Associations with Male Multiple Sclerosis Patients in Erbil Province. Zanco Journal of Pure and Applied Sciences, 33(1), 21–26. https://doi.org/10.21271/ZJPAS.33.1.3