HLA-DRB1*1501 and Spinal Cord Magnetic Resonance Imaging Lesions in Multiple Sclerosis

M.H. Sombekke; C. Lukas; J.B.A. Crusius; D. Tejedor; J. Killestein; D. Arteta; A Martinez; B.M.J. Uitdehaag; D.L. Knol; S. Pena; J.J.G. Geurts; P.L. de Jager; F. Barkhof; H. Vrenken; C.H. Polman

doi:https://doi.org/10.1001/archneurol.2009.278

HLA-DRB1*1501 and Spinal Cord Magnetic Resonance Imaging Lesions in Multiple Sclerosis

M.H. Sombekke, C. Lukas, J.B.A. Crusius, D. Tejedor, J. Killestein, D. Arteta, A Martinez, B.M.J. Uitdehaag, D.L. Knol, S. Pena, J.J.G. Geurts, P.L. de Jager, F. Barkhof, H. Vrenken, C.H. Polman

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

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 DNAmaterial, 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.Weassessed 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 singlenucleotide 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. ©2009 American Medical Association. All rights reserved.

Original language	English
Pages (from-to)	1531-1536
Journal	Archives of neurology
Volume	66
Issue number	12
DOIs	https://doi.org/10.1001/archneurol.2009.278
Publication status	Published - 2009

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https://doi.org/10.1001/archneurol.2009.278

Cite this

Sombekke, M. H., Lukas, C., Crusius, J. B. A., Tejedor, D., Killestein, J., Arteta, D., Martinez, A., Uitdehaag, B. M. J., Knol, D. L., Pena, S., Geurts, J. J. G., de Jager, P. L., Barkhof, F., Vrenken, H., & Polman, C. H. (2009). HLA-DRB1*1501 and Spinal Cord Magnetic Resonance Imaging Lesions in Multiple Sclerosis. Archives of neurology, 66(12), 1531-1536. https://doi.org/10.1001/archneurol.2009.278

@article{171ba8d1fd344ad69500bc44ff6e0da6,

title = "HLA-DRB1*1501 and Spinal Cord Magnetic Resonance Imaging Lesions in Multiple Sclerosis",

abstract = "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 DNAmaterial, 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.Weassessed 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 singlenucleotide 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. {\textcopyright}2009 American Medical Association. All rights reserved.",

author = "M.H. Sombekke and C. Lukas and J.B.A. Crusius and D. Tejedor and J. Killestein and D. Arteta and A Martinez and B.M.J. Uitdehaag and D.L. Knol and S. Pena and J.J.G. Geurts and {de Jager}, P.L. and F. Barkhof and H. Vrenken and C.H. Polman",

note = "J English Article Sombekke, MH, Vrije Univ Amsterdam, Med Ctr, Dept Neurol, De Boelelaan 1117, NL-1081 HV Amsterdam, Netherlands m.sombekke@vumc.nl 41 0 AMER MEDICAL ASSOC CHICAGO 515 N STATE ST, CHICAGO, IL 60610-0946 USA DEC Discipline: Clinical Neurology 529YB",

year = "2009",

doi = "https://doi.org/10.1001/archneurol.2009.278",

language = "English",

volume = "66",

pages = "1531--1536",

journal = "Archives of neurology",

issn = "0003-9942",

publisher = "American Medical Association",

number = "12",

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Sombekke, MH, Lukas, C, Crusius, JBA, Tejedor, D, Killestein, J, Arteta, D, Martinez, A, Uitdehaag, BMJ, Knol, DL, Pena, S, Geurts, JJG, de Jager, PL, Barkhof, F , Vrenken, H & Polman, CH 2009, 'HLA-DRB1*1501 and Spinal Cord Magnetic Resonance Imaging Lesions in Multiple Sclerosis', Archives of neurology, vol. 66, no. 12, pp. 1531-1536. https://doi.org/10.1001/archneurol.2009.278

TY - JOUR

T1 - HLA-DRB1*1501 and Spinal Cord Magnetic Resonance Imaging Lesions in Multiple Sclerosis

AU - Sombekke, M.H.

AU - Lukas, C.

AU - Crusius, J.B.A.

AU - Tejedor, D.

AU - Killestein, J.

AU - Arteta, D.

AU - Martinez, A

AU - Uitdehaag, B.M.J.

AU - Knol, D.L.

AU - Pena, S.

AU - Geurts, J.J.G.

AU - de Jager, P.L.

AU - Barkhof, F.

AU - Vrenken, H.

AU - Polman, C.H.

N1 - J English Article Sombekke, MH, Vrije Univ Amsterdam, Med Ctr, Dept Neurol, De Boelelaan 1117, NL-1081 HV Amsterdam, Netherlands m.sombekke@vumc.nl 41 0 AMER MEDICAL ASSOC CHICAGO 515 N STATE ST, CHICAGO, IL 60610-0946 USA DEC Discipline: Clinical Neurology 529YB

PY - 2009

Y1 - 2009

N2 - 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 DNAmaterial, 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.Weassessed 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 singlenucleotide 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. ©2009 American Medical Association. All rights reserved.

AB - 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 DNAmaterial, 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.Weassessed 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 singlenucleotide 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. ©2009 American Medical Association. All rights reserved.

U2 - https://doi.org/10.1001/archneurol.2009.278

DO - https://doi.org/10.1001/archneurol.2009.278

M3 - Article

SN - 0003-9942

VL - 66

SP - 1531

EP - 1536

JO - Archives of neurology

JF - Archives of neurology

IS - 12

ER -