Sarcoidosis and NOD1 variation with impaired recognition of intracellular Propio

September 14, 2006

Biochim Biophys Acta. 2006 Jul 25; [Epub ahead of print] Links

Sarcoidosis and NOD1 variation with impaired recognition of

intracellular Propionibacterium acnes.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.

Age Dimension Research Center, National Institute of Advanced

Industrial Science and Technology, Tsukuba 305-8566, Japan.

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-kappaB 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-kappaB 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.

PMID: 16935475 [PubMed - as supplied by publisher]

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