Gene variants of adhesion molecules predispose to MS: A case-control study
Abstract
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 (pperm < 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.
How strong is the evidence?
Evidence Hub reads this as a case-control. Its evidence level is 4 of 5 (Low · observational). Observational designs can show an association but not prove cause.
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