Association of interferon gamma and interleukin 10 genes with tuberculosis in Hong Kong Chinese

Abstract

Interferon gamma (IFN-γ) and interleukin 10(IL-10) are believed to play opposing roles in host immunity against mycobacterial infection. IFN-γ 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-γ - 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-γ-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-γ 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-γ-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. © 2005 Nature Publishing Group. All rights reserved.