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

Abstract

Interferon gamma (IFN-g) and interleukin 10 (IL-10) are believed to play opposing roles in host immunity against mycobacterial infection. IFN-g 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-g À179 (G/T), þ 874 (A/T), þ 875 miscrosatellite CA repeats and þ 4766 (C/T), and IL-10 À1082 (A/G), À819 (C/T) and À592 (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-g-producing þ 874 A/A genotype was significantly over-represented in the patient group (Po0.001, OR ¼ 3.79, 95% CI ¼ 1.93-7.45). We identified 10 alleles in the IFN-g CA repeats and observed a significant difference in allele frequency distribution between patients and controls (Po0.001). By grouping alleles into 12 and non-12 CA repeats, the non-12/non-12 genotype yielded a similar significant result (Po0.001, OR ¼ 4.56, 95% CI ¼ 2.21-9.43) as observed in þ 874 A/A genotype. Weak associations of the IL-10 GCC/À genotype (P ¼ 0.04) and the low IFN-g-producing A/A genotype (P ¼ 0.06) with TB relapse/extrapulmonary cases were found. This study suggests the possible role of interferon gamma in TB susceptibility.

Independent and joint effects of the IL-6 and IL-10 gene polymorphisms in pulmonary tuberculosis among the Chinese Han population

“…For example, in Cambodia, the -1082 A>G polymorphism was found to be associated with susceptibility to TB (Delgado et al, 2002;Ben-Selma et al, 2011), whereas no significance could be inferred from the -819 C>T gene polymorphism (Ma et al, 2010). The IL-10 gene polymorphism was considered to be a potential risk factor for TB in the Hong Kong Chinese population (Tso et al, 2005). However, this was not observed in studies of Gambian (Delgado et al, 2002), Egyptian children (Mosaad et al, 2010), and Macedonian (Trajkov et al, 2009) populations.…”

Analysis of interleukin-10 gene polymorphisms and hepatitis C susceptibility in Pakistan

“…IL-10/ GTA: ATA diplotype were more common in controls than in patients so individuals with this genetic makeup are less likely to develop HCV. Previous investigations have shown that IL-10/GCC: GCC or haplotypes having the G allele correlate with higher levels of IL-10 production after stimulation, which leads to the suppression of IFN-α and hence favors the development of HCV [14,28]. Contradictory to our results, IL-10 haplotypes and diplotypes were not distributed differently between healthy controls and HCV cases in different reports from Japan, Caucasian and Italy, the results may be differ due to different ethnicity of studied populations [24,26,27,29,30].…”

Association between RANTES functional polymorphisms and tuberculosis in Hong Kong Chinese

“…2 Studies of the concordance rate of TB among monozygotic and dizygotic twins supported the importance of host genetic factors in determining the development of disease. 3 Our group has previously identified the association between interleukin-12B (IL12B) 4 and interferon-gamma (IFN-g) 5 genetic polymorphisms and TB. We reason that functional polymorphisms of those key cytokine genes which regulate the human immune response against MTB will influence the individual's susceptibility to developing clinical disease after infection.…”