Heterogeneity at the HLA-DRB1 allelic variation locus does not influence multiple sclerosis disease severity, brain atrophy or cognition

Anneke Van Der Walt, Jim Stankovich, M. Bahlo, Bruce V Taylor, IAF Van Der Mei, Simon J Foote, J. P. Rubio, Trevor J Kilpatrick, H. Butzkueven

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25 Citations (Scopus)

Abstract

Background: HLA-DRB1*1501 (DR15) and other HLA class II alleles increase the risk of developing multiple sclerosis (MS). However, the contribution of genetic heterogeneity to the clinical course of MS remains controversial. We examined the influence of DR15 and other common DRB1 alleles (DRB1*01 (DR1), DRB1*03 (DR3) and DRB1*04 (DR4) on MS severity in a large, Australian, population-based cohort. Methods: We studied the association between common HLA-DRB1 alleles and genotypes and age of onset as well as three clinical disease severity descriptors: Multiple Sclerosis Severity Score, progression index), and the interval between the first and second attack in 978 patients with relapsing remitting MS and secondary progressive MS. We assessed cognition using the Symbol Digit Modalities Test in 811 patients and brain atrophy using the linear magnetic resonance imaging marker, the intercaudate ratio, in 745 patients. Results: Carrying DR15 significantly decreased the age of MS onset by 3.2 years in homozygotes and 1.3 years in heterozygotes. Carrying the HLA-DR15, -DR1, -DR3 or -DR4 alone or in combination did not affect clinical disease severity, cognition or cerebral atrophy. Conclusions: This study confirms that heterogeneity of HLA-DRB1 does not influence disease outcome in relapsing MS patients, with the exception of a younger age of onset in HLA-DR15 carriers.

Original languageEnglish
Pages (from-to)344-352
Number of pages9
JournalMultiple Sclerosis
Volume17
Issue number3
DOIs
Publication statusPublished - 2011
Externally publishedYes

Keywords

  • 1501, multiple sclerosis
  • brain atrophy
  • cognition
  • HLA-DRB1
  • severity

Cite this

Van Der Walt, Anneke ; Stankovich, Jim ; Bahlo, M. ; Taylor, Bruce V ; Van Der Mei, IAF ; Foote, Simon J ; Rubio, J. P. ; Kilpatrick, Trevor J ; Butzkueven, H. / Heterogeneity at the HLA-DRB1 allelic variation locus does not influence multiple sclerosis disease severity, brain atrophy or cognition. In: Multiple Sclerosis. 2011 ; Vol. 17, No. 3. pp. 344-352.
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abstract = "Background: HLA-DRB1*1501 (DR15) and other HLA class II alleles increase the risk of developing multiple sclerosis (MS). However, the contribution of genetic heterogeneity to the clinical course of MS remains controversial. We examined the influence of DR15 and other common DRB1 alleles (DRB1*01 (DR1), DRB1*03 (DR3) and DRB1*04 (DR4) on MS severity in a large, Australian, population-based cohort. Methods: We studied the association between common HLA-DRB1 alleles and genotypes and age of onset as well as three clinical disease severity descriptors: Multiple Sclerosis Severity Score, progression index), and the interval between the first and second attack in 978 patients with relapsing remitting MS and secondary progressive MS. We assessed cognition using the Symbol Digit Modalities Test in 811 patients and brain atrophy using the linear magnetic resonance imaging marker, the intercaudate ratio, in 745 patients. Results: Carrying DR15 significantly decreased the age of MS onset by 3.2 years in homozygotes and 1.3 years in heterozygotes. Carrying the HLA-DR15, -DR1, -DR3 or -DR4 alone or in combination did not affect clinical disease severity, cognition or cerebral atrophy. Conclusions: This study confirms that heterogeneity of HLA-DRB1 does not influence disease outcome in relapsing MS patients, with the exception of a younger age of onset in HLA-DR15 carriers.",
keywords = "1501, multiple sclerosis, brain atrophy, cognition, HLA-DRB1, severity",
author = "{Van Der Walt}, Anneke and Jim Stankovich and M. Bahlo and Taylor, {Bruce V} and {Van Der Mei}, IAF and Foote, {Simon J} and Rubio, {J. P.} and Kilpatrick, {Trevor J} and H. Butzkueven",
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Heterogeneity at the HLA-DRB1 allelic variation locus does not influence multiple sclerosis disease severity, brain atrophy or cognition. / Van Der Walt, Anneke; Stankovich, Jim; Bahlo, M.; Taylor, Bruce V; Van Der Mei, IAF; Foote, Simon J; Rubio, J. P.; Kilpatrick, Trevor J; Butzkueven, H.

In: Multiple Sclerosis, Vol. 17, No. 3, 2011, p. 344-352.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Heterogeneity at the HLA-DRB1 allelic variation locus does not influence multiple sclerosis disease severity, brain atrophy or cognition

AU - Van Der Walt, Anneke

AU - Stankovich, Jim

AU - Bahlo, M.

AU - Taylor, Bruce V

AU - Van Der Mei, IAF

AU - Foote, Simon J

AU - Rubio, J. P.

AU - Kilpatrick, Trevor J

AU - Butzkueven, H.

PY - 2011

Y1 - 2011

N2 - Background: HLA-DRB1*1501 (DR15) and other HLA class II alleles increase the risk of developing multiple sclerosis (MS). However, the contribution of genetic heterogeneity to the clinical course of MS remains controversial. We examined the influence of DR15 and other common DRB1 alleles (DRB1*01 (DR1), DRB1*03 (DR3) and DRB1*04 (DR4) on MS severity in a large, Australian, population-based cohort. Methods: We studied the association between common HLA-DRB1 alleles and genotypes and age of onset as well as three clinical disease severity descriptors: Multiple Sclerosis Severity Score, progression index), and the interval between the first and second attack in 978 patients with relapsing remitting MS and secondary progressive MS. We assessed cognition using the Symbol Digit Modalities Test in 811 patients and brain atrophy using the linear magnetic resonance imaging marker, the intercaudate ratio, in 745 patients. Results: Carrying DR15 significantly decreased the age of MS onset by 3.2 years in homozygotes and 1.3 years in heterozygotes. Carrying the HLA-DR15, -DR1, -DR3 or -DR4 alone or in combination did not affect clinical disease severity, cognition or cerebral atrophy. Conclusions: This study confirms that heterogeneity of HLA-DRB1 does not influence disease outcome in relapsing MS patients, with the exception of a younger age of onset in HLA-DR15 carriers.

AB - Background: HLA-DRB1*1501 (DR15) and other HLA class II alleles increase the risk of developing multiple sclerosis (MS). However, the contribution of genetic heterogeneity to the clinical course of MS remains controversial. We examined the influence of DR15 and other common DRB1 alleles (DRB1*01 (DR1), DRB1*03 (DR3) and DRB1*04 (DR4) on MS severity in a large, Australian, population-based cohort. Methods: We studied the association between common HLA-DRB1 alleles and genotypes and age of onset as well as three clinical disease severity descriptors: Multiple Sclerosis Severity Score, progression index), and the interval between the first and second attack in 978 patients with relapsing remitting MS and secondary progressive MS. We assessed cognition using the Symbol Digit Modalities Test in 811 patients and brain atrophy using the linear magnetic resonance imaging marker, the intercaudate ratio, in 745 patients. Results: Carrying DR15 significantly decreased the age of MS onset by 3.2 years in homozygotes and 1.3 years in heterozygotes. Carrying the HLA-DR15, -DR1, -DR3 or -DR4 alone or in combination did not affect clinical disease severity, cognition or cerebral atrophy. Conclusions: This study confirms that heterogeneity of HLA-DRB1 does not influence disease outcome in relapsing MS patients, with the exception of a younger age of onset in HLA-DR15 carriers.

KW - 1501, multiple sclerosis

KW - brain atrophy

KW - cognition

KW - HLA-DRB1

KW - severity

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DO - 10.1177/1352458510389101

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SP - 344

EP - 352

JO - Multiple Sclerosis Journal

JF - Multiple Sclerosis Journal

SN - 1352-4585

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