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A Genetic-Epidemiological Case-control Study of HLA-DQB1*05 and Multiple Sclerosis in Tehran | ||
| Journal of Genetic Resources | ||
| مقالات آماده انتشار، پذیرفته شده، انتشار آنلاین از تاریخ 29 تیر 1404 اصل مقاله (455.85 K) | ||
| نوع مقاله: Research Article | ||
| شناسه دیجیتال (DOI): 10.22080/jgr.2025.29691.1442 | ||
| نویسندگان | ||
| Fatemeh Khabiri؛ Roohollah Nakhaei Sistani* | ||
| Department of Cellular and Molecular Biology, Faculty of Chemistry, University of Kashan, Kashan, Isfahan, Iran | ||
| تاریخ دریافت: 23 اردیبهشت 1404، تاریخ بازنگری: 21 مرداد 1404، تاریخ پذیرش: 12 تیر 1404 | ||
| چکیده | ||
| Multiple sclerosis (MS) is a long-term, immune-mediated disease that affects the central nervous system, characterized by gradual myelin degradation and the development of lesions within the brain and spinal cord. Genetic predisposition, particularly involving human leukocyte antigen (HLA) genes, plays a pivotal role in MS susceptibility. The HLA-DQB1*05 allele has been hypothesized to influence MS risk, though its role in diverse populations remains underexplored. This study investigates the association between the HLA-DQB1*05 allele and MS in the Tehran population, aiming to elucidate its protective or risk-conferring effects in an Iranian context. A case-control study was conducted with 290 participants, comprising 160 healthy controls and 130 MS patients diagnosed according to the McDonald criteria. Peripheral blood samples were collected, and genomic DNA was extracted using the salting-out method. The presence of the HLA-DQB1*05 allele was determined using sequence-specific amplification polymerase chain reaction (SAP-PCR). Statistical analysis revealed a striking disparity in allele frequency: 52.5% of controls carried HLA-DQB1*05, compared to only 14.6% of MS patients (p< 0.001). The odds ratio (OR) for MS risk in allele-negative individuals was 6.46 (95% CI: 3.63-11.50), underscoring a robust protective effect. Chi-square analysis confirmed that neither age (p= 0.41) nor gender (p= 0.53) significantly influenced this association. Further analysis demonstrated a gene-dose effect: homozygous carriers of HLA-DQB1*05 had twice the protective advantage (OR: 0.15) compared to heterozygotes (OR: 0.30), suggesting allele dosage critically modulates MS risk. These findings align with global studies on HLA genes but highlight population-specific variations, as the protective effect of HLA-DQB1*05 in Tehran contrasts with reports of neutral or risk-conferring effects in other cohorts. This study provides compelling evidence that HLA-DQB1*05 significantly reduces MS susceptibility in the Tehran population, likely through immune-modulatory mechanisms. The allele’s dose-dependent protection and population-specific role underscore the importance of genetic context in MS research. Future work should explore functional mechanisms and validate these findings in larger, multi-ethnic cohorts. | ||
| کلیدواژه‌ها | ||
| Autoimmune disease؛ HLA-DQB1*05؛ Multiple sclerosis؛ SAP-PCR | ||
| مراجع | ||
|
Abbas, A. K., & Lichtman, A. H. (2025). Basic immunology: Functions and disorders of the immune system (6th ed.). Elsevier.
Amirzargar, A., Mytilineos, J., Farjadian, S., Doroudchi, M., Scherer, S., Opelz, G., & Ghaderi, A. (2001). Human leukocyte antigen class II allele frequencies and haplotype association in Iranian normal population. Human Immunology, 62(11), 1234–1238. https://doi.org/10.1016/S0198-8859(01)00320-2
Ascherio, A., & Munger, K. L. (2007). Environmental risk factors for multiple sclerosis. Part I: The role of infection. Annals of Neurology, 61(4), 288-299. https://doi.org/10.1002/ana.21117
Čierny, D., Lehotský, J., Kantorová, E., Sivák, Š., Javor, J., Kurča, E., Dobrota, D., Michalik, J. (2015). The association of HLA-DRB1 and HLA-DQB1 alleles with genetic susceptibility to multiple sclerosis in the Slovak population. Neurological Research, 37(12),1060–1067. https://doi.org/10.1080/01616412.2015.1115212
Compston, A., & Coles, A. (2008). Multiple sclerosis. The Lancet, 372(9648), 1502-1517. https://doi.org/10.1016/S0140-6736(08)61620-7
De Jager, P. L., Chibnik, L. B., Cui, J., Reischl, J., Lehr, S., Simon, K. C., ... & Hafler, D. A. (2009). Integration of genetic risk factors into a clinical algorithm for multiple sclerosis susceptibility: A weighted genetic risk score. The Lancet Neurology, 8(12), 1111-1119. https://doi.org/10.1016/S1474-4422(09)70275-2
Dendrou, C. A., Fugger, L., & Friese, M. A. (2015). Immunopathology of multiple sclerosis. Nature Reviews Immunology, 15(9), 545-558. https://doi.org/10.1038/nri3871
Devi-Marulkar, P., Moraes-Cabe, C., Campagne, P., Corre, B., Meghraoui-Kheddar, A., Bondet, V., ... & Michel, F. (2021). Altered immune phenotypes and HLA-DQB1 gene variation in multiple sclerosis patients failing interferon β treatment. Frontiers in Immunology, 12, 640891. https://doi.org/10.3389/fimmu.2021.640891
Elhami, S. R., Mohammad, K., Sahraian, M. A., & Eftekhar, H. (2011). A 20-year incidence trend (1989-2008) and point prevalence (March 20, 2009) of multiple sclerosis in Tehran, Iran: A population-based study. Neuroepidemiology, 36(3), 141-147. https://doi.org/10.1159/000325174
Etemadifar, M., Sajjadi, S., Nasr, Z., Firoozeei, T. S., Abtahi, S. H., Akbari, M., & Fereidan-Esfahani, M. (2013). Epidemiology of multiple sclerosis in Iran: A systematic review. European Neurology, 70(5-6), 356-363. https://doi.org/10.1159/000355140
Farjadian S, Ota M, Inoko H, Ghaderi A. (2009). The genetic relationship among Iranian ethnic groups: an anthropological view based on HLA class II gene polymorphism. Mol Biol Rep, 36(7): 1943-1950. https://doi.org/10.1007/s11033-008-9403-4
Frohman, E. M., Racke, M. K., & Raine, C. S. (2006). Multiple sclerosis-The plaque and its pathogenesis. New England Journal of Medicine, 354(9), 942-955. https://doi.org/10.1056/NEJMra052130
Ghabaee, M., Bayati, A., Amri Saroukolaei, S., Sahraian, M. A., Sanaati, M. H., Karimi, P., et al. (2009). Analysis of HLA DR2 & DQ6 (DRB11501, DQA10102, DQB10602) haplotypes in Iranian patients with multiple sclerosis. Cellular and Molecular Neurobiology, 29(1), 109–114. https://doi.org/10.1007/s10571-008-9302-1
Ghanbari Mardasi, F., Khorram Khorshid, H. R., & Shafiei, M. (2014). HLA-DR and -DQ allele frequencies in Iranian patients with multiple sclerosis. Immunology Letters, 160(1), 50-53. https://doi.org/10.1016/j.imlet.2014.03.007
Jones, E. Y., Fugger, L., Strominger, J. L., & Siebold, C. (2006). MHC class II proteins and disease: A structural perspective. Nature Reviews Immunology, 6(4), 271-282. https://doi.org/10.1038/nri1805
Khdair, S. I., Al-Khareisha, L., Abusara, O. H., Hammad, A. M., & Khudair, A. (2025). HLA-class II genes association with multiple sclerosis: An immunogenetic prediction among multiple sclerosis Jordanian patients. PLoS One, 20(2), e0318824. https://doi.org/10.1371/journal.pone.0318824
Link, J, Kockum, I, Lorentzen, ÅR, Lie, BA, Celius, EG, Mengel-Jørgensen, J, Hillert, J, Olsson, T, Masterman, T, Olsson, M (2012). Importance of Human Leukocyte Antigen (HLA) Class I and II alleles on the risk of multiple sclerosis. PLoS ONE, 7(5), e36779. https://doi.org/10.1371/journal.pone.0036779
Mack, S. J., Udell, J., Cohen, F., Osoegawa, K., Hawbecker, S. K., Noonan, D. A., Ladner, M. B., Goodridge, D., Trachtenberg, E. A., Oksenberg, J. R., & Erlich, H. A. (2018). High-resolution HLA analysis reveals independent class I haplotypes and amino-acid motifs protective for multiple sclerosis. Genes and Immunity, 20(4), 308–326. https://doi.org/10.1038/s41435-017-0006-8
Maghbooli Z, Sahraian MA, Moghadasi AN. (2020). Multiple sclerosis and human leukocyte antigen genotypes: Focus on the Middle East and North Africa region. Multiple Sclerosis Journal - Experimental, Translational and Clinical. 6(1):2055217319881775. https://doi:10.1177/2055217319881775
McKay, K. A., Manouchehrinia, A., & Biström, M. (2008). HLA-DQB1*05 and susceptibility to MS: An update on the protective role across populations. Multiple Sclerosis Journal, 14(2), 234-240. https://doi.org/10.1177/1352458507084279
Milo, R., & Kahana, E. (2010). Multiple sclerosis: Geoepidemiology, genetics and the environment. Autoimmunity Reviews, 9(5), A387-A394. https://doi.org/10.1016/j.autrev.2009.11.010
Polman, C. H., Reingold, S. C., Banwell, B., Clanet, M., Cohen, J. A., Filippi, M., Fujihara, K., Havrdova, E., Hutchinson, M., Kappos, L., Lublin, F. D., Montalban, X., O'Connor, P., Sandberg-Wollheim, M., Thompson, A. J., Waubant, E., Weinshenker, B., & Wolinsky, J. S. (2011). Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Annals of Neurology, 69(2), 292-302. https://doi.org/10.1002/ana.22366
Sahraian, M. A., Khorramnia, S., Ebrahim, M. M., Moinfar, Z., Lotfi, J., & Pakdaman, H. (2013). Multiple sclerosis in Iran: A demographic study of 8,000 patients and changes over time. European Neurology, 70(1-2), 83-87. https://doi.org/10.1159/000350166
Schmidt, H., Williamson, D., & Ashley-Koch, A. (2007). HLA-DR15 haplotype and multiple sclerosis: A HuGE review. American Journal of Epidemiology, 165(10), 1097-1109. https://doi.org/10.1093/aje/kwk118
Shahbazi, M., Ebadi, H., Fathi, D., Roshandel, D., Mohamadhosseni, M., Tahmasebi, A., Shahbazi, S., Zamani, M., Rashidbaghan, A. (2010). HLA-DRB11501 intensifies the impact of IL-6 promoter polymorphism on the susceptibility to multiple sclerosis in an Iranian population. Multiple Sclerosis, 16(10), 1173–1177. https://doi.org/10.1177/1352458510376177
Suguna, S. G., Kamble, S. P., & Bharatha, A. (2014). Genomic DNA isolation from human whole blood samples by non enzymatic salting out method. International Journal of Scientific and Research Publications, 4(5), 1-4.
Varzi, A.-M., Zargooshi, J., Akrami, S. M., & Kamali, K. (2016). HLA-DQB1 allele and haplotype frequencies in the Lak population of Iran. Iranian Journal of Public Health, 45(4), 494-500. https://pubmed.ncbi.nlm.nih.gov/27189628 | ||
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