title: Relationship between SNPs and expression level for candidate genes in rheumatoid arthritis.
abstract: OBJECTIVE
  The study of polymorphisms of genes differentially expressed may lead to the identification of putative causal genetic variants in multifactorial diseases such as rheumatoid arthritis (RA). Based on preceding transcriptomic results, we genotyped 10 single nucleotide polymorphisms (SNPs) belonging to six genes (S100A8, RNASE2, PGLYRP1, RUNX3, IL2RB, and LY96) showing the highest fold change (> 1.9) when level of expression was compared between RA patients and controls. These SNPs were then analysed to evaluate their role in RA.
  
  
  METHODS
  The relationship between gene expression and genotypes of SNPs was first investigated by Kruskal-Wallis and Mann-Whitney tests in RA patients and controls. The genetic association of these SNPs with RA were then analysed using family-based association tests in trio families.
  
  
  RESULTS
  We found that RNASE2 gene expression was related to rs2013109 genotypes in 14 RA patients (p = 0.030). The association study in a discovery sample of 200 French trio families revealed a significant association with RA for one SNP, PGLYRP1-rs2041992 (p = 0.019); this association was stronger in trios where RA patients carried the HLA-DRB1 shared epitope (SE) (p = 0.003). However, this association was not found in a replication sample of 240 European trio families (p = 0.6).
  
  
  CONCLUSIONS
  Family-based association tests did not reveal an association between RA and any SNP of the candidate genes tested. However, RNASE2 gene expression was differentially expressed in RA patients considering a sequence polymorphism. This result led us to highlight the potential disease-specific regulation for this candidate gene in RA.
authors.affiliation: GenHotel-EA3886, Evry-Val d'Essonne University, Evry-Genopole , France.
authors.forename: M
authors.initials: M
authors.lastname: Fodil
authors.forename: V H
authors.initials: VH
authors.lastname: Teixeira
authors.forename: V
authors.initials: V
authors.lastname: Chaudru
authors.forename: P
authors.initials: P
authors.lastname: Hilliquin
authors.forename: S
authors.initials: S
authors.lastname: Bombardieri
authors.forename: A
authors.initials: A
authors.lastname: Balsa
authors.forename: R
authors.initials: R
authors.lastname: Westhovens
authors.forename: P
authors.initials: P
authors.lastname: Barrera
authors.forename: H
authors.initials: H
authors.lastname: Alves
authors.forename: P
authors.initials: P
authors.lastname: Migliorin
authors.forename: T
authors.initials: T
authors.lastname: Bardin
authors.forename: F
authors.initials: F
authors.lastname: Cornelis
authors.forename: A
authors.initials: A
authors.lastname: Boudjema
authors.forename: E
authors.initials: E
authors.lastname: Petit-Teixeira
mesh_terms: D000328:Adult; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D040501:Calgranulin A / Q000235:genetics; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics; D016207:Cytokines / Q000235:genetics*; D047208:Eosinophil-Derived Neurotoxin / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D053646:Interleukin-2 Receptor beta Subunit / Q000235:genetics; D051218:Lymphocyte Antigen 96 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D059467:Transcriptome; D055815:Young Adult
chemical_list: D040501:Calgranulin A; D050677:Core Binding Factor Alpha 3 Subunit; D016207:Cytokines; D005819:Genetic Markers; C508020:IL2RB protein, human; D053646:Interleukin-2 Receptor beta Subunit; C495377:LY96 protein, human; D051218:Lymphocyte Antigen 96; C491878:PGLYRP1 protein, human; C493729:Runx3 protein, human; D047208:Eosinophil-Derived Neurotoxin; C479221:RNASE2 protein, human