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HLA-DRB1*1501 and Spinal Cord Magnetic Resonance Imaging Lesions in Multiple Sclerosis
Madeleine H. Sombekke, MD;
Carsten Lukas, MD;
J. Bart A. Crusius, PhD;
Diego Tejedor, PhD;
Joep Killestein, MD, PhD;
David Arteta, PhD;
Antonio Martínez, PhD;
Bernard M. J. Uitdehaag, MD, PhD;
Dirk L. Knol, PhD;
A. Salvador Peña, MD, PhD;
Jeroen J. G. Geurts, PhD;
Philip L. De Jager, MD, PhD;
Frederik Barkhof, MD, PhD;
Hugo Vrenken, PhD;
Chris H. Polman, MD, PhD
Arch Neurol. 2009;66(12):1531-1536.
Background Multiple sclerosis (MS) is a heterogeneous neurologic disease with extensive variation with respect to the most affected central nervous system region (brain vs spinal cord).
Objective To test the hypothesis that this variation in lesion location (brain vs spinal cord) might be (partially) genetically determined.
Design Candidate gene study.
Setting Academic research.
Patients Patients were selected for the availability of DNA material, clinical variables, and brain and spinal cord magnetic resonance images (evaluating T2-weighted lesion load in the brain and the number of spinal cord lesions).
Main Outcome Measures For genotyping, we used a DNA chip containing a set of genes mentioned in previous publications noting their relation to different phenotypes of MS. We assessed the association between brain and spinal cord abnormalities and the genotypes of the patients.
Results One hundred fifty patients were included in the analysis. Five single-nucleotide polymorphisms within the major histocompatibility complex region were associated with the number of focal abnormalities in the spinal cord. The most significant was rs3135388 (surrogate marker for the HLA-DRB1*1501 allele). Carriers of HLA-DRB1*1501 had a median of 4 spinal cord lesions compared with 2 lesions for noncarriers (P < .001). No significant association was noted between the single-nucleotide polymorphisms and T2-weighted lesion load in the brain.
Conclusions Carriership of HLA-DRB1*1501 (via rs3135388) was associated with the extent of focal abnormalities in the spinal cord. Spinal cord lesions might be an explanation for increased MS disease severity in patients carrying HLA-DRB1*1501.
Author Affiliations: Departments of Neurology (Drs Sombekke, Killestein, Uitdehaag, and Polman), Radiology (Drs Lukas, Geurts, Barkhof, and Vrenken), Pathology (Drs Crusius, Peña, and Geurts), Epidemiology and Biostatistics (Drs Uitdehaag and Knol), and Physics and Medical Technology (Dr Vrenken), VU University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands; Department of Diagnostic and Interventional Radiology, St Josef Hospital, Ruhr University, Bochum, Germany (Dr Lukas); Progenika Biopharma, SA, Derio, Spain (Drs Tejedor, Arteta, and Martínez); and Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, and Partners Center for Personalized Genetic Medicine, Boston, Massachusetts (Dr De Jager).
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