Association of MBL2, TLR1, TLR2, and TLR6 Polymorphisms with Production of IFN-γ and IL-12 in BCG Osteitis Survivors.

Interferon-gamma (IFN-γ) is a key cytokine in defense against mycobacteria, including Bacillus Calmette-Guérin (BCG). Mannose-binding lectin (MBL) and Toll-like receptors (TLRs) are pattern-recognizing molecules of innate immunity. The aim of the present study was to investigate the relationship between polymorphisms in MBL, TLR1, TLR2, and TLR6 encoding genes and stimulated IFN-γ and interleukin-12 (IL-12) ex vivo production in BCG osteitis survivors.,Data on single nucleotide polymorphisms (SNPs) in the MBL2 gene and TLR1, TLR2, and TLR6 genes were available from 132 former BCG osteitis patients, and data on ex vivo IFN-γ and IL-12 production were available from 115 and 118 patients, respectively. The present study is a secondary analysis of these available data. In an earlier study, we were able to characterize low IFN-γ and low IL-12 producers after BCG+IL-12 or BCG+IFN-γ stimulations, respectively.,Three patients had the homozygous variant MBL2 genotype, and one of them was a low IFN-γ producer (both concentration and response <5 percentile). The heterozygous variant MBL2 genotype showed no association with IFN-γ or IL-12 production. The TLR2 variant genotype was present in 14 subjects; 28.6% of them were low IFN-γ producers vs. 7.8% of those 103 with the TLR2 wild genotype (p=0.037). TLR1 or TLR6 polymorphisms had no significant associations with stimulated ex vivo IFN-γ or IL-12 production.,Preliminary evidence was found that variant genotypes of the MBL2 gene (if homozygous) and variant genotypes of the TLR2 gene (only heterozygotes present) are associated with low IFN-γ production.