Linkage between Toll‐like receptor (TLR) 2 promotor and intron polymorphisms: functional effects and relevance to sarcoidosis

Summary The intracellular pathogens Propionibacterium acnes and Mycobacterium tuberculosis have been leading suspects as the cause of sarcoidosis, a systemic disorder characterized by the formation of non‐caseating granulomas. Toll‐like receptor (TLR) 2 is important in the innate immune response against both pathogens, and is therefore of interest in sarcoidosis research. In the present study, three single nucleotide polymorphisms and one dinucleotide repeat polymorphism in the TLR‐2 gene were genotyped in 419 sarcoidosis patients, divided into a study cohort and a validation cohort, and 196 healthy controls. In the study cohort we found a significant increase in prevalence of the AA‐genotype at promotor location −16934 in patients with chronic disease compared to patients with acute/self‐remitting sarcoidosis (34·5% versus 15·9%, respectively, P = 0·006, Pc = 0·019). These results could not be confirmed in our validation cohort, implicating a possible role for TLR‐2 genetics in only a small percentage of sarcoidosis patients. Furthermore, linkage was found between the promotor polymorphism −16934 A/T and the number of GT repeats in intron 1 (P