Abstract
BackgroundMultiple sclerosis is a chronic inflammatory, demyelinating disease of the central nervous system. Recent genome-wide studies have revealed more than 110 single nucleotide polymorphisms as associated with susceptibility to multiple sclerosis, but their functional contribution to disease development is mostly unknown.ResultsConsistent allelic imbalance was observed for rs907091 in IKZF3 and rs11609 in IQGAP1, which are in strong linkage disequilibrium with the multiple sclerosis associated single nucleotide polymorphisms rs12946510 and rs8042861, respectively. Using multiple sclerosis patients and healthy controls heterozygous for rs907091 and rs11609, we showed that the multiple sclerosis risk alleles at IKZF3 and IQGAP1 are expressed at higher levels as compared to the protective allele. Furthermore, individuals homozygous for the multiple sclerosis risk allele at IQGAP1 had a significantly higher total expression of IQGAP1 compared to individuals homozygous for the protective allele.ConclusionsOur data indicate a possible regulatory role for the multiple sclerosis-associated IKZF3 and IQGAP1 variants. We suggest that such cis-acting mechanisms may contribute to the multiple sclerosis association of single nucleotide polymorphisms at IKZF3 and IQGAP1.Electronic supplementary materialThe online version of this article (doi:10.1186/s12863-016-0367-4) contains supplementary material, which is available to authorized users.
Highlights
Multiple sclerosis is a chronic inflammatory, demyelinating disease of the central nervous system
We investigate three single nucleotide polymorphisms (SNPs) in Multiple sclerosis (MS) associated regions for the presence of allelic imbalance (AI); (i) the MS-associated SNP rs11052877, which lies in the coding region of cluster of differentiation 69 (CD69), (ii) the rs907091 SNP in the coding region of IKAROS family zinc finger 3 (IKZF3) and in strong linkage disequilibrium (LD) with the MSassociated rs12946510 and (iii) the rs11609 SNP located in the coding region of IQGAP1and in strong LD with the MS-associated rs8042861
Patients and controls A total of 140 MS patients were available for the study, of whom 92 were heterozygous for at least one of the three SNPs studied; i.e. rs11052877 (CD69), rs907091 (IKZF3) and rs11609 (IQGAP1), and included in the analyses
Summary
Multiple sclerosis is a chronic inflammatory, demyelinating disease of the central nervous system. Recent genome-wide studies have revealed more than 110 single nucleotide polymorphisms as associated with susceptibility to multiple sclerosis, but their functional contribution to disease development is mostly unknown. Through recent large genome - wide association studies (GWASs) followed up by genome-wide analyses of immune-related loci, more than 110 non-HLA genetic variants were. Genetic variants may have an influence on the expression of target genes, and the MS-association of the polymorphisms identified through the genetic screens is likely to be the result of such regulatory properties. Analysis to unravel whether MS-associated SNPs exert cis-acting regulation is an important step in MS research.
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