The Blau syndrome gene is not a major risk factor for sarcoidosis

Background, A genetic predisposition to sarcoidosis has long been postulate d, although no specific susceptibility genes are known. Candidate genes for the two granulomatous inflammatory disorders with clinical similarities to sarcoidosis, Blau syndrome and Crohn's disease, have been localized to a 4 0 centimorgan region spanning the chromosome 16 centromere. Patients and me thods: Using a sample of 35 African-American sibling pairs, who both had cl inically confirmed sarcoidosis, we tested for genetic linkage between the 1 6p12-q21 interval (the likely location of the Blau syndrome gene) and sarco idosis. Results: We found no evidence for linkage to any of the eight marke rs we tested in the 16p12-q21 interval. Ninety percent of the 16p12-q21 reg ion had a LOD score < -2 for a dominant gene conferring a relative risk of 3 or greater for sarcoidosis. One hundred percent of the region had a LOD s core < -2 for a dominant gene with a relative risk of 3.5 or greater or rec essive gene with relative risk of 2.5 or greater. Based on simulation resul ts we could not exclude a dominant gene with relative risk < 5 at the 0.05 significance level, nor a recessive gene with relative risk < 3, over the e ntire 16p12-q21 interval. Conclusions: While the clinical similarities betw een Blau Syndrome and sarcoidosis suggest genetic homogeneity between the d isorders, we found no evidence for linkage of sarcoidosis to the Blau syndr ome locus. Our exclusion results suggest that the Blau Syndrome gene does n ot have a major effect on sarcoidosis susceptibility.