Analysis of an interferon-gamma gene dinucleotide-repeat polymorphism in Nordic multiple sclerosis patients

The proinflammatory cytokine interferon (IFN)-gamma has been shown to influ ence the course of multiple sclerosis (MS). The IFN-gamma (IFNG) contains a multiallelic dinucleotide repeat in intron I. To investigate whether allel es at this locus influence susceptibility to MS, we performed linkage and f amilial association analyses on 100 sibling pairs from four Nordic countrie s and case-control association analysis on 220 intermediately disabled spor adic MS patients and 266 controls. To determine the effect of the polymorph ism on disease outcome, we compared genotype frequencies in the most and le ast disabled octiles of a total cohort of 913 cases. We also measured IFN-g amma mRNA levels in unstimulated peripheral blood mononuclear cells from 46 MS patients and 27 controls grouped according to IFNG intron I genotype. B oth nonparametric linkage analysis and transmission disequilibrium testing of the 100 sibling Pairs produced negative results. Genotype frequencies fo r intermediate-MS patients did not differ significantly from those for cont rols; nor did genotype frequencies in the benign-MS octile differ significa ntly from those in the severe-MS octile. Comparison of IFN-gamma mRNA level s in genotype-conditioned subgroups revealed no significant differences. Th us, alleles at the IFNG intron I dinucleotide repeat appear to affect neith er MS susceptibility and severity nor IFN-gamma mRNA expression in vivo.