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Interferon gamma (IFN-?) and interleukin 10 (IL-10) are believed to play opposing roles in host immunity against mycobacterial infection. IFN-?activates macrophages, while IL-10 downregulates the expression of T helper type 1 cytokines, MHC class II antigens and costimulatory molecules on macrophages. Associations of IFN-?-179 (G/T),+874 (A/T),+875 miscrosatellite CA repeats and+4766 (C/T), and IL-10-1082 (A/G),-819 (C/T) and-592 (C/A) with tuberculosis (TB) were investigated in 385 HIV-negative patients and 451 controls in a Hong Kong Chinese population. The frequency of a low IFN-?-producing+874 A/A genotype was significantly over-represented in the patient group (P<0.001, OR=3.79, 95%CI=1.93-7.45). We identified 10 alleles in the IFN-?CA repeats and observed a significant difference in allele frequency distribution between patients and controls (P<0.001). By grouping alleles into 12 and non-12 CA repeats, the non-12/non-12 genotype yielded a similar significant result (P<0.001, OR=4.56, 95%CI=2.21-9.43) as observed in+874 A/A genotype. Weak associations of the IL-10 GCC/-genotype (P=0.04) and the low IFN-?-producing A/A genotype (P=0.06) with TB relapse/extrapulmonary cases were found. This study suggests the possible role of interferon gamma in TB susceptibility.Genes and Immunity (2005) 6, 358-363. doi:10.1038/sj.gene.6364189 Published online 7 April 2005 [ABSTRACT FROM AUTHOR]