ITGA4 polymorphisms and susceptibility to multiple sclerosis

Catherine King, Izaura M. Roos, Alfredo Antiguedad, Ana M. Aransay, Jan Hillert, Koen Vandenbroeck

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

In multiple sclerosis (MS), α4β1 integrin, also known as Very Late Antigen 4 (VLA4), facilitates migration of leukocytes across the blood brain barrier. Several studies suggest that expression of α4 integrin may be increased in MS patients compared to controls, and down-regulation or antagonism of α4 integrin may be associated with immunomodulatory treatment success. We analysed association of 13 single nucleotide polymorphisms (SNPs) in the gene encoding α4 integrin (ITGA4) with susceptibility to MS in two distinct populations comprising cases and controls from the Basque Country in northern Spain (352 patients; 235 controls) and Nordic countries (1119 patients; 1235 controls). Carriage of the C allele of the ITGA4 promoter SNP rs1449263 was independently and weakly increased in MS patients from each population compared to respective controls (P = 0.037 in Basque; and P = 0.042 in Nordic cohorts), though these associations were lost upon application of permutation correction. Meta-analysis of rs1449263*C carriage revealed a Mantel-Haenszel common OR of 1.26 (95% CI 1.06-1.49; P = 0.0069). Though our data only modestly argue for a role of ITGA4 in determining susceptibility to MS, we suggest that further examination of this gene, particularly the promoter region, is warranted.

Original languageEnglish
Pages (from-to)151-157
Number of pages7
JournalJournal of Neuroimmunology
Volume189
Issue number1-2
DOIs
Publication statusPublished - 1 Sep 2007

Keywords

  • Genetic
  • ITGA4
  • Integrin
  • Multiple sclerosis
  • Natalizumab
  • Polymorphism

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Neurology
  • Clinical Neurology

Cite this

King, C., Roos, I. M., Antiguedad, A., Aransay, A. M., Hillert, J., & Vandenbroeck, K. (2007). ITGA4 polymorphisms and susceptibility to multiple sclerosis. Journal of Neuroimmunology, 189(1-2), 151-157. https://doi.org/10.1016/j.jneuroim.2007.07.006