Interleukin-10 and Tumor Necrosis Factor-α Gene Polymorphisms in Tuberculosis

Abstract

Tuberculosis (TB), caused by Mycobacterium tuberculosis, is an infectious disease in humans killing nearly three million people and eight million cases annually. The cytokines TNF-alpha and IL-10 have been implicated in the pathogenesis of TB. Certain single nucleotide polymorphisms within the promoter region of the IL10 and TNF genes have been associated with altered levels of circulating IL10 and TNF-alpha. We analyzed TNF-alpha (-308 G/A, -238 G/A, -376 G/A) and IL10 (-1,082 G/A, -819 C/T, -592 C/A) polymorphisms in 128 patients with TB and 80 healthy subjects using by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). A significant association was found between TB and -1,082 G allele (Pc: 0.000, O.R 2.22, 95% CI 1.45-3.41). Significant difference was observed in IL10 GCC and ACC haplotypes distribution between TB and control subjects (Pc: 0.000, O.R 2.22, 95% CI 1.45-3.41; Pc: 0.004, O.R 0.53, 95% CI 0.35-0.81). No statistically significant association was found between IL-10 -819 C/T, TNF-alpha 308 G/A, -238 G/A, -376 G/A polymorphisms, functional TNFalpha/IL-10 genotypes and TB. Our findings suggest that IL-10 1082 G/A alleles or haplotypes containing these alleles may influence the Th1/Th2 balance and hence may play a role in TB susceptibility and increase risk of developing disease. This polymorphism may be one of the many genetic factors affecting disease outcome.

The NRAMPI, VDR and TNF-α gene polymorphisms in Iranian tuberculosis patients: the study on host susceptibility

“…Although, the polymorphisms in position,-238, and -308 have been extensively studied in tuberculosis [24,25]. Previous studies demonstrated no association of particular allele or genotype of TNF-α with TB in different Asians, i.e., Indian, Turkish and Thai population [6,16,26]. In this study, only TNF-α-308A allele was associated with pulmonary TB (Table 1).…”

“…In TNF-α promoter gene (-238 and -308) two SNPs have been described, and the presence of A at -308 has been associated with the high TNF-α production [6,15,19].Today, several polymorphisms have been found in TNF gene at position -1031, -863, -857, -575, -376, -308, -244, -238, and +70 [19]. Although, the polymorphisms in position,-238, and -308 have been extensively studied in tuberculosis [24,25].…”

“…This suggest that besides the Mycobacteria itself, the host genetic factors may determine the differences in host susceptibility to TB [3]. Recently, a number of genes have been investigated in various case control studies, among which the natural resistance-associated macrophage protein (NRAMP1, also called as solute carrier 11a1; Slc11a1), vitamin-D receptor (VDR) and tumor necrosis factor-alpha (TNF-α) genes are thought to be important in the intracellular killing of Mycobacteria [4][5][6]. The NRAMP1 is the human homologue of the mouse Nramp1 gene, and is present on human chromosome 2q35 [7,8].…”

“…The TNF-α gene that encodes the cytokines TNF-α is located within the class III region of the MHC. TNF-α is an important mediator in the inflammatory response against TB and its production controlled both transcriptionally and post transcriptionally [6,11,12]. Polymorphisms in the NRAMP1, VDR and TNF-α genes have been associated in susceptibility to tuberculosis in different ethnic groups [13][14][15], but the results have been inconclusive.…”

Biomedical Importance of Host Genetic Factors in Infectious Diseases

“…Haplotype -308A-238G have been reported as a protective factor for TB, but susceptibility factor for RA, SLE, and primary SS; opposite association of TNF polymorphism with autoimmunity and TB, suggested that autoimmune diseases are a consequence of natural selection for enhanced TB resistance. Ates et al, (2008), detected TNF-(-308 G/A, -238 G/A, -376 G/A) and IL10 (-1,082 G/A, -819 C/T, -592 C/A) polymorphisms in patients with TB and healthy controls. A significant association was found between TB and -1,082 G allele.…”