Therefore, we can conclude that there is no association between the CARD15 gene and the development or a special phenotype of sarcoidosis in our cohort.
This is the first report of a CARD15 mutation-positive patient with Blau syndrome who exhibited interstitial lung disease, a feature historically considered absent from Blau syndrome, while typical of the adult form of sarcoidosis.
Analysis of exon 4 of the CARD15 gene containing mutations associated with Blau syndrome was performed by polymerase chain reaction and sequencing of genomic DNA from 52 patients with histologically verified sarcoidosis.
The frequency of CARD15 mutations is not increased in ethnic Danish patients with sarcoidosis, and heterozygosity for such mutations apparently has no influence on the course of disease.
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.
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.
The aim of this work was to determine the frequencies of the three major NOD2/CARD 15 gene mutations (R702W, G908R and 1007fsinC) in a series of 76 subjects affected by IPF, and to compare them with those found in three groups of controls: a group with sarcoidosis (a disorder in which an involvement of the NOD2/CARD15 gene has already been investigated and rejected in different ethnic groups; 67 subjects) and two groups of healthy subjects (218 and 208 subjects, respectively), matched for gender, age, and ethnicity.