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A single nucleotide polymorphism (SNP), +874T/A, in the first intron of the interferon-gamma (IFN-gamma) gene, has presented associations with human susceptibility to tuberculosis (TB) in some ethnic populations, but not in others. In this population-based case-control study with adult TB patients from Houston, Texas, we found no significant differences of + 874T/A genotypic frequencies between cases and ethnically-matched controls or between advanced forms of TB disease (extra-pulmonary involvement or presence of cavitary disease) and pulmonary TB. Given possible sample size limitations, our results suggest that the IFN-gamma +874T/A mutation has no association with TB susceptibility or TB disease severity.

Screening for latent tuberculosis infection (LTBI) with Mantoux tuberculin skin test (TST) has many limitations, including false-positive results due to exposure to Mycobacterium other than tuberculosis (TB) and BCG vaccination. A total of 474 adult inmates in a county jail were screened for LTBI using TST and a new ESAT-6/CFP-10 peptide-based whole-blood gamma interferon (IFN-gamma) assay. LTBI prevalence was 9.0 and 5.4% as determined by TST and IFN-gamma assay, respectively. Overall, agreement between test results was 90% (kappa = 0.25). Positive TST results were significantly associated with increased age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.01 to 1.08), African-American ethnicity (OR, 4.97; 95% CI, 1.58 to 15.68), foreign birth (OR, 20.20; 95% CI, 4.21 to 97.02) and prior incarceration (OR, 6.19; 95% CI, 1.48 to 25.95). Positive IFN-gamma assay results were significantly associated with African-American ethnicity (OR, 5.58; 95% CI, 1.16 to 26.74). Factors associated with statistically significant discordance between TST and IFN-gamma assay results were African-American ethnicity (OR, 0.29; 95% CI, 0.11 to 0.77), foreign birth (OR, 0.23; 95% CI, 0.07-0.80), and prior incarceration (OR, 0.06; 95% CI, 0.01-0.50). Among subjects born in the United States, African-American ethnicity was the only variable significantly associated with positive test results for both TST (OR, 4.26; 95% CI, 1.38 to 13.16) and IFN-gamma assay (OR, 5.74; 95% CI, 1.19 to 27.75) and remained associated with statistically significant discordance between TST and IFN-gamma assay results. The reactivity of the new IFN-gamma assay is unaffected by prior BCG vaccination or serial TSTs but may be diminished in African-Americans. Future longitudinal studies are needed to assess the sensitivity and specificity of this new assay in detecting LTBI.

Setting: Houston Tuberculosis Initiative (HTI) and Baylor College of Medicine, Houston, Texas., Objective: To further explore the association between the polymorphisms of NRAMP1 and human susceptibility/resistance to tuberculosis (TB), specifically to determine whether the reported association shown for blacks and Asians holds true for Caucasian populations., Design: In a case-control study, 135 adult Caucasian TB patients and 108 adult Caucasian HIV-seronegative non-TB controls were analyzed for the association between the polymorphisms in NRAMP1 gene and clinical TB., Results: Heterozygote at 5'(GT)n, a dinucleotide repeat polymorphism in the promoter of NRAMP1, was observed at significantly higher frequencies among HIV-negative patients with pulmonary TB (41.6%; OR 2.02; 95%CI 1.11-3.64), extra-pulmonary TB (66.7%; OR 4.80; 95%CI 1.34-17.15), and HIV-seropositive TB patients (50%; OR 3.77; 95%CI 1.33-10.66) in comparison with the controls (27.8%). Homozygotes (GT)(10,10) were over-represented among HIV-positive TB patients (18.2%; OR 6.86; 95%CI 1.55-30.21) compared to the controls (5.5%)., Conclusion: These findings suggest that the 5'(GT)n polymorphism of NRAMP1 modifies TB susceptibility in this Caucasian population, and could possibly be related to the site of infection among HIV-negative individuals and HIV-coinfected TB.