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. CONCLUSION: 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.
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 sarcoidosispatients 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. CONCLUSION: 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: M Veltkamp; P A H M Wijnen; C H M van Moorsel; G T Rijkers; H J T Ruven; M Heron; O Bekers; A M E Claessen; M Drent; J M M van den Bosch; J C Grutters Journal: Clin Exp Immunol Date: 2007-06-12 Impact factor: 4.330
Authors: Jessica L Werner; Sylvia G Escolero; Jeff T Hewlett; Tim N Mak; Brian P Williams; Yoshinobu Eishi; Gabriel Núñez Journal: Am J Respir Cell Mol Biol Date: 2017-01 Impact factor: 6.914
Authors: M Veltkamp; C H M Van Moorsel; G T Rijkers; H J T Ruven; J M M Van Den Bosch; J C Grutters Journal: Clin Exp Immunol Date: 2010-08-19 Impact factor: 4.330
Authors: M Schürmann; R Kwiatkowski; M Albrecht; A Fischer; J Hampe; J Müller-Quernheim; E Schwinger; S Schreiber Journal: Clin Exp Immunol Date: 2008-04-16 Impact factor: 4.330
Authors: H L Rosenzweig; M M Jann; T T Glant; T M Martin; S R Planck; W van Eden; P J S van Kooten; R A Flavell; K S Kobayashi; J T Rosenbaum; M P Davey Journal: J Leukoc Biol Date: 2009-01-07 Impact factor: 4.962
Authors: Z Daniil; V Mollaki; F Malli; A Koutsokera; K M Antoniou; P Rodopoulou; K Gourgoulianis; E Zintzaras; G Vassilopoulos Journal: Mol Biol Rep Date: 2013-05-11 Impact factor: 2.316