Gene variants of adhesion molecules predispose to MS: A case-control study.

Objective: To examine the effect of variants in genes encoding molecules that are implicated in leukocyte trafficking into the CNS on the development of MS.

Methods: A total of 389 Greek MS cases and 336 controls were recruited by 3 MS centers in Cyprus and Greece. In total, 147 tagging single nucleotide polymorphisms across 9 genes encoding for P-selectin ( SELP ), integrins ( ITGA4 , ITGB1 , and ITGB7 ), adhesion molecules ( ICAM1 , VCAM1 , and MADCAM1) , fibronectin 1 ( FN1 ), and osteopontin ( SPP1 ) were genotyped. The clinical end point of the study was diagnosis of MS according to the 2005 revised McDonald criteria. Permutation analysis was used for adjusting for multiple comparisons.

Results: Overall, 21 variants across SELP , ITGA4 , ITGB1 , ICAM1 , VCAM1 , MADCAM1 , FN1 , and SSP1 genes were each associated with MS ( p perm < 0.05). The most significant were rs3917779 and rs2076074 ( SELP ), rs6721763 ( ITGA4 ), and rs1250258 ( FN1 ), all with a permutation p value of less than 1e-004.

Conclusions: The current study provides preliminary evidence that variants across genes encoding adhesion molecules, responsible for lymphocyte adhesion and trafficking within the CNS, are implicated in the risk of developing MS.