ITGA4 polymorphisms and susceptibility to multiple sclerosis

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.