Interferon‐γ and interleukin‐12 production in relation to gene polymorphisms in bacillus Calmette–Guérin osteitis

Abstract

Background: Interferon-c (IFN-c) and interleukin-12 (IL-12) play a crucial role in the defense against mycobacteria, and in the response to bacillus Calmette-Gu erin (BCG) vaccination. We have previously reported clinical and outcome data of 222 BCG osteitis cases diagnosed in 1960-1988 in Finland. The immunological and genetic reports have been based on 132 blood samples obtained in 2007-2008. Methods: We compared IFNc rs2430561 and rs35314021, IL12A rs568408 and rs2243115, and IL12B rs3212227 single-nucleotide polymorphisms (SNP) between 132 BCG osteitis patients and 99 population-based controls. In addition, stimulated production of IFN-c and IL-12 in cell culture was evaluated in relation to the presence of IFNc and IL12 wild versus variant genotypes, respectively. Results: The distributions of IFNc rs2430561, IFNc rs35314021, IL12A rs568408, IL12A rs2243115 and IL12B rs3212227 SNP did not differ between BCG osteitis patients and Finnish population-based controls. For IFNc rs2430561, IFNc rs35314021 and IL12A rs2243115, the negative result was confirmed by comparing the minor allele frequencies (MAF) in BCG osteitis cases with those in the publicly available genome aggregation database, including data for 3,472 Finnish persons. Instead, for IL12A rs568408 and IL12B rs3212227, the comparison of MAF in BCG osteitis cases with those in population-based and in aggregation-based controls gave conflicting results. The presence of the wild versus variant genotype had no significant association with IL-12 or IFN-c production in BCG-stimulated cell cultures. Conclusion: IFNc gene polymorphisms did not show any association with BCG osteitis after newborn vaccination.

The sixty‐year story of Finnish Bacillus Calmette‐Guérin (BCG) osteitis

“…Fresh whole blood samples were obtained from 132 former Finnish BCG osteitis patients when they were 21‐49 years old, and we were able to reveal a group of subjects with low ex vivo IFN‐γ and/or IL‐12 production in BCG‐stimulated cell cultures 21 . However, the studied polymorphisms in the IFNγ , IL12A or IL12B genes did not differ between BCG osteitis cases and population controls nor between low IFN‐γ or IL‐12 producers and normal producers in the BCG osteitis cohort 26 …”

“…21 However, the studied polymorphisms in the IFNγ, IL12A or IL12B genes did not differ between BCG osteitis cases and population controls nor between low IFN-γ or IL-12 producers and normal producers in the BCG osteitis cohort. 26 Instead, IL17A gene variations were associated with osteitis risk in the Finnish BCG cohort. The rs2275913 polymorphism was associated with an increased BCG osteitis risk in the genotype analyses 27 and the rs4711998, rs8193036 and rs2275913 polymorphisms in the haplotype analyses.…”