title: Allelic expression analysis of the osteoarthritis susceptibility locus that maps to chromosome 3p21 reveals cis-acting eQTLs at GNL3 and SPCS1.
abstract: BACKGROUND
  An osteoarthritis (OA) susceptibility locus has been mapped to chromosome 3p21, to a region of high linkage disequilibrium encompassing twelve genes. Six of these genes are expressed in joint tissues and we therefore assessed whether any of the six were subject to cis-acting regulatory polymorphisms active in these tissues and which could therefore account for the association signal.
  
  
  METHODS
  We measured allelic expression using pyrosequencing assays that can distinguish mRNA output from each allele of a transcript single nucleotide polymorphism. We assessed RNA extracted from the cartilage and other joint tissues of OA patients who had undergone elective joint replacement surgery. A two-tailed Mann-Whitney exact test was used to test the significance of any allelic differences.
  
  
  RESULTS
  GNL3 and SPCS1 demonstrated significant allelic expression imbalance (AEI) in OA cartilage (GNL3, mean AEI = 1.04, p = 0.0002; SPCS1, mean AEI = 1.07, p < 0.0001). Similar results were observed in other tissues. Expression of the OA-associated allele was lower than that of the non-associated allele for both genes.
  
  
  CONCLUSIONS
  cis-acting regulatory polymorphisms acting on GNL3 and SPCS1 contribute to the OA association signal at chromosome 3p21, and these genes therefore merit further investigation.
authors.affiliation: Institute of Cellular Medicine, Musculoskeletal Research Group, Newcastle University, Newcastle-upon-Tyne, UK. fiona.gee@newcastle.ac.uk.
authors.forename: Fiona
authors.initials: F
authors.lastname: Gee
authors.forename: Clare F
authors.initials: CF
authors.lastname: Clubbs
authors.forename: Emma V A
authors.initials: EV
authors.lastname: Raine
authors.forename: Louise N
authors.initials: LN
authors.lastname: Reynard
authors.forename: John
authors.initials: J
authors.lastname: Loughlin
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D022981:Allelic Imbalance; D002356:Cartilage / Q000378:metabolism / Q000473:pathology; D018797:Cell Cycle Proteins; D002893:Chromosomes, Human, Pair 3; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics*; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D010003:Osteoarthritis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics; D040641:Quantitative Trait Loci; D014157:Transcription Factors / Q000235:genetics
chemical_list: D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; C469949:GNL3 protein, human; D008565:Membrane Proteins; D009687:Nuclear Proteins; C102195:PBRM1 protein, human; C575745:POC1A protein, human; D011506:Proteins; D014157:Transcription Factors; C000590229:signal peptidase complex subunit 1, human; D019204:GTP-Binding Proteins