Interferon-γ Gene (T874A and G2109A) Polymorphisms Are Associated With Microscopy-positive Tuberculosis

Genetic susceptibility to tuberculosis includes several unknown yet different loci each contributing to a small extent. Intronic polymorphisms within the interferon- g (IFN-g) gene IFNG Tþ 874A and IFNG Gþ 2109A correlate with the IFN-g production in vitro, and the frequency of potential high IFN-g producers was previously reported by others to be lower in patients than in controls from Sicily. The aim of this study was to determine whether there is an association between polymorphisms in the IFN-g gene and predisposition to tuberculosis. We analysed two IFNG SNPs (Tþ 874A and Gþ 2109A) in patients (n¼ 253) hospitalized in Rijeka (Croatia) and controls (n¼ 519) from the same area. One fifth of the controls were healthy contacts of the diseased, and the rest were blood donors. IFNG alleles, their predicted haplotypes or genotypes were not associated with disease susceptibility. Thus, we could not reproduce results from Sicilian case-control study. However, T/Tþ 874 (possible high IFN-g producer) and þ 874A/A (putative low producer) genotypes were associated with microscopically positive– negative forms of disease. Haplotypes (Tþ 874A and Gþ 2109A) based on a prediction by software PHASE and subsequent genotype analysis corroborated these findings. Patients had significantly higher frequency of genotypes without T at þ 874 (AA/AA ; AA/AG and AG/AG) in microscopy or bacterial culture-positive groups compared with their negative counterparts.These data suggest an association with disease severity rather than susceptibility to tuberculosis in Croatian Caucasian population.