Differential expression, and genetic association, of CD58 in Swedish multiple sclerosis patients

Abstract

We report additional genetic and transcriptomic evidence for the role of CD58 (LFA-3) in multiple sclerosis (MS) susceptibility using a Swedish case-control material, with a result that closely mimics that of De Jager et al. (1). This gene was originally selected for further assessment because of implications in MS susceptibility (2), and because of reduced expression in the cerebrospinal fluid (CSF) of MS patients compared to controls investigated using the Affymetrix Human Genome U133 plus 2 arrays, where 2 probe sets for CD58 detected fold changes of 0.65–0.8 (P = 3.1 × 10−3 and 4.4 × 10−2). The current study included 1,077 patients and 1,217 blood-donor controls, all residing in the Stockholm area and of Scandinavian ancestry. Markers from HapMap Phase II were selected to capture most variance around CD58, and Sequenom methodology was utilized to assess genotypes at 12 SNPs. Association was tested by using logistic regression in R, validating the association of several CD58 SNPs. Most notably, the strongest effect was seen by the correlated (r2 of 0.52) alleles rs10924103G and rs12044852A, in analogy with previous results (1), showing odds ratios of 0.73 and 0.72 in multiplicative models (P = 8.3 × 10−5 and 4.3 × 10−4) and an etiological fraction of 45%. Thus, we are able to contribute to the knowledge of CD58 in MS by, in a Swedish material, reporting lowered expression of this costimulatory molecule in the CSF of MS patients, and confirming the genetic association.