Sarcoidosis and NOD1 variation with impaired recognition of intracellular Propionibacterium acnes

Tsuyoshi Tanabe, Ikuo Ishige, Yoshimi Suzuki, Yukie Aita, Asuka Furukawa, Yuki Ishige, Keisuke Uchida, Takashige Suzuki, Tamiko Takemura, Soichiro Ikushima, Masaru Oritsu, Tetsuji Yokoyama, Yukari Fujimoto, Koichi Fukase, Naohiro Inohara, Gabriel Nunez, Yoshinobu Eishi

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Abstract

Sarcoidosis is a systemic granulomatous disease of unknown etiology. NOD2 mutations have been shown to predispose to granulomatous diseases, including Crohn's disease, Blau syndrome, and early-onset sarcoidosis, but not to adult sarcoidosis. We found that intracellular Propionibacterium acnes, a possible causative agent of sarcoidosis, activated NF-κB in both NOD1- and NOD2-dependent manners. Systematic search for NOD1 gene polymorphisms in Japanese sarcoidosis patients identified two alleles, 796G-haplotype (156C, 483C, 796G, 1722G) and 796A-haplotype (156G, 483T, 796A, 1722A). Allelic discrimination of 73 sarcoidosis patients and 215 healthy individuals showed that the frequency of 796A-type allele was significantly higher in sarcoidosis patients and the ORs were significantly elevated in NOD1-796G/A and 796A/A genotypes (OR [95% CI] = 2.250 [1.084, 4.670] and 3.243 [1.402, 7.502], respectively) as compared to G/G genotype, showing an increasing trend across the 3 genotypes (P = 0.006 for trend). A similar association was found when 52 interstitial pneumonia patients were used as disease controls. Functional studies showed that the NOD1 796A-allele was associated with reduced expression leading to diminished NF-κB activation in response to intracellular P. acnes. The results indicate that impaired recognition of intracellular P. acnes through NOD1 affects the susceptibility to sarcoidosis in the Japanese population.

Original languageEnglish
Pages (from-to)794-801
Number of pages8
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1762
Issue number9
DOIs
Publication statusPublished - 2006 Sep
Externally publishedYes

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Keywords

  • Granulomatous disease
  • NF-κB
  • NOD2
  • TLR2

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine
  • Biophysics

Cite this

Tanabe, T., Ishige, I., Suzuki, Y., Aita, Y., Furukawa, A., Ishige, Y., Uchida, K., Suzuki, T., Takemura, T., Ikushima, S., Oritsu, M., Yokoyama, T., Fujimoto, Y., Fukase, K., Inohara, N., Nunez, G., & Eishi, Y. (2006). Sarcoidosis and NOD1 variation with impaired recognition of intracellular Propionibacterium acnes. Biochimica et Biophysica Acta - Molecular Basis of Disease, 1762(9), 794-801. https://doi.org/10.1016/j.bbadis.2006.07.006