Interferon-γ (+874 T/A) and interleukin-10 (−1082 G/A) genes polymorphisms are associated with active tuberculosis in the Algerian population of Oran's city

Abstract

Background and aimsPolymorphisms within genes encoding the cytokines involved in anti-tuberculosis immunity have been widely studied and sometimes associated with an increased risk of developing the active form of tuberculosis (TB). This study analyzes for the first time the impact of two polymorphisms, namely IFNG+874 T/A and IL10-1082 G/A, in the Algerian population where tuberculosis is moderately endemic. MethodsThis case–control study included 104 healthy controls and 141 active TB patients: 75 extrapulmonary (EPTB) and 66 pulmonary (PTB). They were all genotyped by refractory mutational system-PCR amplification. In order to measure the functional impact of IFNG+874 T/A on the production rate of IFN-γ, 43 patients performed a QuantiFERON®Gold In-tube test. ResultsThe IFNG+874 AA genotype was associated with a higher risk of developing EPTB (OR = 2.52; 95%CI = 1.23–5.18; p = 0.012) while the IFNG+874 TA genotype was associated with a greater protection (OR = 0.34, 95%CI = 0.16–0.74; p = 0.006) which was further characterized by a high production of IFN-γ (p = 0.001). Similarly, the allele A of SNP IL10-1082 G/A, especially in its homozygous form (AA), were overrepresented in PTB patients (p = 0.010 and 0.019, respectively). The combination of both susceptibility genotypes (AA/AA) was strongly associated with risk of development of active TB (OR = 8.58; 95% C.I = 1.95–37.70, p = 0.004). This susceptibility combination was only significant in men regarding PTB (OR = 11.05; 95% C.I = 1.32–92.72, p = 0.027). Additionally, IFNG+874 TA and IL10-1082G∗ genotypes combination was mostly encountered in men controls and conferred the highest protection rate against EPTB (OR = 0.25; 95% C.I = 0.08–0.76, p = 0.015). ConclusionThese two cytokines genes polymorphisms are associated with active TB susceptibility in the Algerian population. They act synergistically in terms of protection and susceptibility regarding the two forms of the disease. Moreover, these associations were more marked among males suggesting a potential role of gender.