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NEUROLOGY 2003;61:1245-1249
© 2003 American Academy of Neurology

{alpha}B-Crystallin genotype has impact on the multiple sclerosis phenotype

T. van Veen, MSc, L. van Winsen, MD, J. B.A. Crusius, MSc, N. F. Kalkers, MD PhD, F. Barkhof, MD PhD, A. S. Peña, MD PhD, C. H. Polman, MD PhD and B. M.J. Uitdehaag, MD PhD

From the Departments of Neurology (Drs. van Winsen, Kalkers, Polman, and Uidehaag, T. van Veen) and Clinical Epidemiology and Biostatistics (Dr. Uidehaag, T. van Veen), Laboratory of Immunogenetics (Dr. Peña, J.B.A. Crusius), and MS-MRI Center (Dr. Barkhof), VU University Medical Center, Amsterdam, the Netherlands.

Address correspondence and reprint requests to Ms. Tineke van Veen, Department of Molecular Cell Biology, VU Medical Center, PO Box 7057, 1007 MB Amsterdam, the Netherlands; e-mail: T.vanveen{at}VUMC.NL

Background: Both multiple sclerosis (MS) susceptibility and MS clinical phenotype are in part genetically determined. {alpha}B-Crystallin is a candidate autoantigen in MS, and there are three polymorphisms in the promoter region of the encoding gene (CRYAB): at positions -C249G, -C650G, and -A652G.

Methods: These polymorphisms were studied in sporadic cases of MS, assessing disease susceptibility, clinical phenotype, and MRI appearance.

Results: The CRYAB polymorphisms influenced susceptibility as well as disease expression in MS.

Conclusion: Carriers of the rare allele CRYAB–650*C had an increased likelihood of a noninflammatory, neurodegenerative phenotype characterized by a relatively rapid, primary progressive clinical disease course.

Received November 13, 2002. Accepted in final form July 29, 2003.




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