title: Allelic imbalance of multiple sclerosis susceptibility genes IKZF3 and IQGAP1 in human peripheral blood.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  Consistent 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.
  
  
  CONCLUSIONS
  Our 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.
authors.affiliation: Department of Neurology, Oslo University Hospital, Oslo, Norway. keshari.pankaj@gmail.com.|Institute of Clinical Medicine, University of Oslo, Oslo, Norway. keshari.pankaj@gmail.com.
authors.forename: Pankaj K
authors.initials: PK
authors.lastname: Keshari
authors.affiliation: Department of Neurology, Oslo University Hospital, Oslo, Norway.|Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Hanne F
authors.initials: HF
authors.lastname: Harbo
authors.affiliation: Norwegian Multiple Sclerosis Registry and Biobank, Department of Neurology, Haukeland University Hospital, Bergen, Norway.|KG Jebsen Centre for MS-research, Department of Clinical Medicine, University of Bergen, Bergen, Norway.
authors.forename: Kjell-Morten
authors.initials: KM
authors.lastname: Myhr
authors.affiliation: Norwegian Multiple Sclerosis Registry and Biobank, Department of Neurology, Haukeland University Hospital, Bergen, Norway.|KG Jebsen Centre for MS-research, Department of Clinical Medicine, University of Bergen, Bergen, Norway.
authors.forename: Jan H
authors.initials: JH
authors.lastname: Aarseth
authors.affiliation: Department of Neurology, Oslo University Hospital, Oslo, Norway.|Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Steffan D
authors.initials: SD
authors.lastname: Bos
authors.affiliation: Department of Neurology, Oslo University Hospital, Oslo, Norway.
authors.forename: Tone
authors.initials: T
authors.lastname: Berge
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D022981:Allelic Imbalance; D016022:Case-Control Studies; D005260:Female; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D060005:Genotyping Techniques; D006801:Humans; D051740:Ikaros Transcription Factor / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000175:diagnosis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012680:Sensitivity and Specificity; D055815:Young Adult; D020703:ras GTPase-Activating Proteins / Q000235:genetics*
chemical_list: C106285:IKZF3 protein, human; C101203:IQ motif containing GTPase activating protein 1; D020703:ras GTPase-Activating Proteins; D051740:Ikaros Transcription Factor
keywords: Allele specific expression; CD69; IKZF3; IQGAP1; Multiple sclerosis; eQTL