title: CARD15/NOD2, CD14, and toll-like receptor 4 gene polymorphisms in Greek patients with sarcoidosis.
abstract: BACKGROUND
  Sarcoidosis, similarly to Crohn's disease (CD), is a complex inflammatory disease of unknown etiology. The belief that a genetic susceptibility to the development of sarcoidosis exists was derived from observations of familial clustering of sarcoidosis cases and racial differences in disease prevalence. Taking into account the remarkable similarity in the immunopathophysiology of sarcoidosis and CD, and in further exploring the genetic background of sarcoidosis, we study gene polymorphisms known for their implication in CD. These polymorphisms are in the CARD15/NOD2 gene (R702W, G908R and 3020insC), as well as mutations in the promoter of the CD14 gene (T/C at position -159) and in the TLR4 gene (Asp299Gly and Thr399Ile).
  
  
  METHODS
  DNA was obtained from 100 sarcoidosis patients and 150 healthy individuals. Genotyping was performed by allele specific PCR or by PCR-RFLP analysis.
  
  
  RESULTS
  Although CARD 15/NOD2 mutations were more frequent in cases than in controls, the difference was significant only for the G908R polymorphism (p = 0.024). Interestingly, the same was recorded with reference to the T allele (p = 0.002) and TT genotype (p = 0.017) frequencies of the CD14 promoter. No differences were observed in the 299Gly and 399Ile allele frequencies between patients and controls. Finally, the co-existence of a mutation in the CARD15/NOD2 and the CD14 genes was associated with sarcoidosis at a higher level of significance than any of these mutations separately.
  
  
  CONCLUSIONS
  Our results suggest that the G908R mutation of the CARD15/NOD2 gene, as well as the T allele and TT genotype of the CD14 promoter are associated with increased susceptibility for developing sarcoidosis.
authors.affiliation: Department of Histology-Embryology, School of Medicine, University of Athens, Athens, Greece. mgazouli@med.uoa.gr
authors.forename: Maria
authors.initials: M
authors.lastname: Gazouli
authors.forename: Aimilios
authors.initials: A
authors.lastname: Koundourakis
authors.forename: John
authors.initials: J
authors.lastname: Ikonomopoulos
authors.forename: Elias J
authors.initials: EJ
authors.lastname: Gialafos
authors.forename: Aggeliki
authors.initials: A
authors.lastname: Rapti
authors.forename: Vassilis G
authors.initials: VG
authors.lastname: Gorgoulis
authors.forename: Christos
authors.initials: C
authors.lastname: Kittas
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D005787:Gene Frequency; D006115:Greece / Q000453:epidemiology; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000235:genetics*; D009154:Mutation; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012507:Sarcoidosis / Q000453:epidemiology / Q000235:genetics*; D051197:Toll-Like Receptor 4 / Q000235:genetics*
chemical_list: D018950:Lipopolysaccharide Receptors; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4