Published: 2016-12-29

Genetic variants and magnetic resonance imaging measures in multiple sclerosis: a systematic review

Department of Pediatric Gastroenterology and Metabolic Diseases, Poznan University of Medical Sciences, Poznan, Poland
Department of General Radiology and Neuroradiology, Poznan University of Medical Sciences, Poznan, Poland
Department of Biology and Medical Parasitology, Poznan University of Medical Sciences, Poznan, Poland
Department of Biology and Medical Parasitology, Poznan University of Medical Sciences, Poznan, Poland
Department of Clinical Pathomorphology, Poznan University of Medical Sciences, Poznan, Poland
Department of Ophthalmology, Poznan University of Medical Sciences, Poznan, Poland
Department of Neurology, Poznan University of Medical Sciences, Poland
Department of Pediatric Gastroenterology and Metabolic Diseases, Poznan University of Medical Sciences, Poznan, Poland
brain spinal cord cortical atrophy lesion polymorphism snp haplotype imaging


Introduction. Although environmental factors play the major role in the etiopathogenesis of multiple sclerosis (MS), genetic factors are implicated as well. We aimed to summarize the current knowledge on the relationship between genetic variants and magnetic resonance (MR) imaging measures in MS.
Material and Methods. A systematic review. In December 2016, Scopus (since the year 1980; including MEDLINE) was searched for studies meeting predefined criteria designed to identify articles regarding: multiple sclerosis, genetic variants, and MR imaging. These were then analyzed to identify publications linking polymorphisms and MR findings.
Results. The search yielded 290 items; 26 were included in the final analysis. Two genome-wide association studies (GWAS) and two projects employing panels of a few dozen of genes of interest provided most of the data. The other publications concerned no more than 5 genes at a time. Twenty studies reported positive findings. The relationship between HLA-DRB1*15:01 or BDNF rs6265 (Val66Met) and the radiologic course of MS was not consistent across the studies. An intersection of the results of the two GWAS yielded: OPCML (rs11223055), PTPRD (rs1953594), and WWOX (rs11150140, rs1116525) (brain atrophy) as well as CDH13 (rs692612) and PLCB1 (rs6118257) (lesion load).
Conclusions. Genetic variants were shown to correlate with MS-related brain atrophy and lesion load. Further research in the field is required.


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  1. Olsson T, Barcellos LF, Alfredsson L. Interactions between genetic, lifestyle and environmental risk factors for multiple sclerosis. Nat Rev Neurol. 2016. doi:10.1038/nrneurol.2016.187.
  2. Scopus Content Coverage Guide. 2016. [accessed on December 16th, 2016]
  3. Allam M, Helmy H, Soliman R, Ali N, El-Shafy S. Association of Interleukin-1 Gene Polymerphism and Multiple Sclerosis. Egypt J Neurol Psychiatry Neurosurg. 2014;51:45–51.
  4. Okuda DT, Srinivasan R, Oksenberg JR, Goodin DS, Baranzini SE, Beheshtian A et al. Genotype-Phenotype correlations in multiple sclerosis: HLA genes influence disease severity inferred by 1HMR spectroscopy and MRI measures. Brain J Neurol. 2009;132:250–9.
  5. Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group. Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLoS Med. 2009;6:e1000097.
  6. Isobe N, Keshavan A, Gourraud P-A, Zhu AH, Datta E, Schlaeger R et al. Association of HLA Genetic Risk Burden With Disease Phenotypes in Multiple Sclerosis. JAMA Neurol. 2016;73:795.
  7. Yaldizli Ö, Sethi V, Pardini M, Tur C, Mok KY, Muhlert N et al. HLA-DRB*1501 associations with magnetic resonance imaging measures of grey matter pathology in multiple sclerosis. Mult Scler Relat Disord. 2016;7:47–52.
  8. Matsushita T, Madireddy L, Sprenger T, Khankhanian P, Magon S, Naegelin Y et al. Genetic associations with brain cortical thickness in multiple sclerosis: DNA variation affects cortical thickness in MS. Genes Brain Behav. 2015;14:217–27.
  9. Huang J, Isobe N, Matsushita T, Yoshimura S, Sato S, Yonekawa T et al. Distinct genetic profiles between Japanese multiple sclerosis patients with and without Barkhof brain lesions. Clin Exp Neuroimmunol. 2013;4:173–80.
  10. Rossi S, Studer V, Moscatelli A, Motta C, Coghe G, Fenu G et al. Opposite Roles of NMDA Receptors in Relapsing and Primary Progressive Multiple Sclerosis. PLoS ONE 2013;8:e67357.
  11. Fera F, Passamonti L, Cerasa A, Gioia MC, Liguori M, Manna I et al. The BDNF Val66Met Polymorphism Has Opposite Effects on Memory Circuits of Multiple Sclerosis Patients and Controls. PLoS ONE 2013;8:e61063.
  12. Inkster B, Strijbis EMM, Vounou M, Kappos L, Radue E-W, Matthews PM et al. Histone deacetylase gene variants predict brain volume changes in multiple sclerosis. Neurobiol Aging. 2013;34:238–47.
  13. Vosslamber S, van der Voort LF, van den Elskamp IJ, Heijmans R, Aubin C, Uitdehaag BMJ et al. Interferon regulatory factor 5 gene variants and pharmacological and clinical outcome of Interferonß therapy in multiple sclerosis. Genes Immun. 2011;12:466–72.
  14. Sombekke MH, Vellinga MM, Uitdehaag BMJ, Barkhof F, Polman CH, Arteta D et al. Genetic Correlations of Brain Lesion Distribution in Multiple Sclerosis: An Exploratory Study. Am J Neuroradiol. 2011;32:695–703.
  15. Ramasamy DP, Ramanathan M, Cox JL, Antulov R, Weinstock-Guttman B, Bergsland N et al. Effect of Met66 allele of the BDNF rs6265 SNP on regional gray matter volumes in patients with multiple sclerosis: A voxel-based morphometry study. Pathophysiology. 2011;18:53–60.
  16. Weinstock-Guttman B, Benedict RHB, Tamano-Blanco M, Ramasamy DP, Stosic M, Polito J et al. The rs2030324 SNP of brain-derived neurotrophic factor (BDNF) is associated with visual cognitive processing in multiple sclerosis. Pathophysiology. 2011;18:43–52.
  17. Xia Z, Chibnik LB, Glanz BI, Liguori M, Shulman JM, Tran D et al. A Putative Alzheimer’s Disease Risk Allele in PCK1 Influences Brain Atrophy in Multiple Sclerosis. PLoS ONE 2010;5:e14169.
  18. Sombekke MH, Lukas C, Crusius JBA, Tejedor D, Killestein J, Arteta D et al. HLA-DRB1*1501 and Spinal Cord Magnetic Resonance Imaging Lesions in Multiple Sclerosis. Arch Neurol. 2009;66.
  19. Baranzini SE, Wang J, Gibson RA, Galwey N, Naegelin Y, Barkhof F et al. Genome-wide association analysis of susceptibility and clinical phenotype in multiple sclerosis. Hum Mol Genet. 2009;18:767–78.
  20. Zivadinov R, Weinstock-Guttman B, Benedict R, Tamano-Blanco M, Hussein S, Abdelrahman N et al. Preservation of gray matter volume in multiple sclerosis patients with the Met allele of the rs6265 (Val66Met) SNP of brain-derived neurotrophic factor. Hum Mol Genet. 2007;16:2659–68.
  21. van Veen T, Nielsen J, Berkhof J, Barkhof F, Kamphorst W, Bö L et al. CCL5 and CCR5 genotypes modify clinical, radiological and pathological features of multiple sclerosis. J Neuroimmunol. 2007;190:157–64.
  22. Kaimen-Maciel DR, Reiche EMV, Brum Souza DG, Frota Comini ER, Bobroff F, Morimoto HK et al. CCR5-Delta32 genetic polymorphism associated with benign clinical course and magnetic resonance imaging findings in Brazilian patients with multiple sclerosis. Int J Mol Med. 2007;20:337–44.
  23. Liguori M, Fera F, Gioia MC, Valentino P, Manna I, Condino F et al. Investigating the role of brain-derived neurotrophic factor in relapsing-remitting multiple sclerosis. Genes Brain Behav. 2007;6:177–83.
  24. Wergeland S, Beiske A, Nyland H, Hovdal H, Jensen D, Larsen JP et al. IL-10 promoter haplotype influence on interferon treatment response in multiple sclerosis. Eur J Neurol. 2005;12:171–5.
  25. Schrijver HM, Crusius JBA, García-González MA, Polman CH, Pena AS, Barkhof F et al. Gender-Related Association Between the<I> TGFB1</I>+869 Polymorphism and Multiple Sclerosis. J Interferon Cytokine Res. 2004;24:536–42.
  26. Zwemmer JNP, Van Veen T, Van Winsen L, Van Kamp GJ, Barkhof F, Polman CH et al. No major association of ApoE genotype with disease characteristics and MRI findings in multiple sclerosis. Mult Scler. 2004;10:272–7.
  27. Vanveen T, Crusius J, Vanwinsen L, Xia B, Barkhof F, Salvadorpena A et al. CTLA-4 and CD28 gene polymorphisms in susceptibility, clinical course and progression of multiple sclerosis. J Neuroimmunol. 2003;140:188–93.
  28. van Veen T, Kalkers N, Crusius JB, van Winsen L, Barkhof F, Jongen PJ, et al. The FAS-670 polymorphism influences susceptibility to multiple sclerosis. J Neuroimmunol. 2002;128:95–100.
  29. Schreiber K, Oturai A, Ryder L, Madsen H, Jorgensen O, Svejgaard A et al. Disease severity in Danish multiple sclerosis patients evaluated by MRI and three genetic markers (HLA-DRB1*1501, CCR5 deletion mutation, apolipoprotein E). Mult Scler. 2002;8:295–8.
  30. Weatherby SJ, Mann CL, Davies MB, Fryer AA, Haq N, Strange RC et al. A pilot study of the relationship between gadolinium-enhancing lesions, gender effect and polymorphisms of antioxidant enzymes in multiple sclerosis. J Neurol. 2000;247:467–70.
  31. Kondo K. Abstracts of the 41st annual meeting of the Japan society of human genetics October 23–25, 1996, Sapporo, Japan. Jpn J Hum Genet. 1997;42:23–167.
  32. Przybek J, Gniatkowska I, Mirowska-Guzel D, Członkowska A. Evolution of diagnostic criteria for multiple sclerosis. Neurol Neurochir Pol. 2015;49:313–21.
  33. Filippi M, Rocca MA, Ciccarelli O, De Stefano N, Evangelou N, Kappos L et al. MRI criteria for the diagnosis of multiple sclerosis: MAGNIMS consensus guidelines. Lancet Neurol. 2016;15:292–303.

How to Cite

Nowak JK, Guzikowska-Ruszkowska I, Łopaciuch J, Jankowska W, Piotrowska E, Dziedzic-Szeszuła E, Kapecka K, Walkowiak J. Genetic variants and magnetic resonance imaging measures in multiple sclerosis: a systematic review. JMS [Internet]. 2016Dec.29 [cited 2020Aug.8];85(4):311. Available from: