Concordance between IFNγ gene +874 A/T polymorphism and interferon-γ expression in a TB-endemic indigenous setting

Abstract

Introduction: Interferon-γ (IFN-γ) plays a crucial role in resistance to mycobacterial diseases; accordingly, variants of the gene encoding this cytokine may be associated with elevated risk of contracting pulmonary tuberculosis (TB). Methods: Blood samples were collected from 135 Warao indigenous individuals with newly diagnosed sputum culture-positive TB. Of these, 24 were diagnosed with active tuberculosis (ATB). The study comprised 111 participants, who were grouped as follows: 1) 14 tuberculin skin test (TST)-positive Warao indigenous individuals and 4 that were QuantiFERON-TBGold In-Tube (QFT-IT) test-positive, collectively comprising the latent TB infection group (LTBI), n = 18), and 2) healthy controls who were QFT-ITand TST-negative, comprising the control group (CTRL, n = 93). Detection of the IFN γ gene (IFNG) +874A/T polymorphism was performed via PCR and quantification of IFNG expression via qPCR. Results: Relative to indigenous and white Americans, ATB and CTRL groups had a higher frequency of the IFNG SNP (+874A): 23 (95.8%) and 108 (97.3%), respectively. Indigenous Warao individuals homozygous for the IFNG (+874) A allele exhibited 3.59-fold increased risk of developing TB (95% confidence interval, 2.60-4.96, p =0.0001). A decreased frequency of the AT genotype was observed in individuals with pulmonary TB (4.16%) and controls (0.90%). The frequency of the TT genotype was decreased among controls (1.80%); none of the patients with TB were found to have this genotype. The differences in IFNG expression between the groups, under unstimulated and stimulated conditions, were not statistically significant. Conclusions: Preliminary results demonstrate concordance between IFNG +874 A/A genotype and low expression of IFNG.

Association of IFN-γ +874 A/T SNP and hypermethylation of the -53 CpG site with tuberculosis susceptibility

“…Thus, AA genotype or A allele have been associated with low levels of IFN-g production, otherwise TT genotype or T allele are associated with higher production of this cytokine, and AT genotype with intermediate levels (Pravica et al, 2000). A significant association between this SNP and TB has been described in several populations around the world, as in the Sicilian, Brazilian, Chinese, Egyptian children, Spanish, Warao indigenous, South Indian and Iranian population (Lio et al, 2002;Lopez-Maderuelo et al, 2003;Tso et al, 2005;Amim et al, 2008;Mosaad et al, 2010;Bhanothu et al, 2015;Beiranvand et al, 2016;Araujo et al, 2017). Moreover, +874 A/ T IFNG polymorphism has been associated with TB and extrapulmonary TB susceptibility in meta-analysis studies (Pacheco et al, 2008;Wei et al, 2017;Mandal et al, 2019;Areeshi et al, 2021).…”

Prognostic value of TNF-a-308 and IFN-g-874 single nucleotide polymorphisms and their plasma levels in patients with aplastic anemia

“…IFN-γ is a key pro-inflammatory cytokine that has a defensive role in host resistance against cancer and also contributes towards essential disease pathology. The IFN-γ gene contains two common polymorphisms, 874 A/T and 875 C/A, which may have functional products following gene transcription [12].…”

Influence of single‐nucleotide polymorphisms in the IFNG towards susceptibility to tuberculosis in a Pakistani population

“…Considerable variation exists in the allele frequencies of cytokine gene polymorphisms among different populations (Bagheri, Abdi-Rad, Omrani, & Khalkhali, 2006), and therefore, unsurprisingly, genetic polymorphisms associated with TB have yielded conflicting results in different ethnic groups (Takiff, 2007). The IFNG polymorphism (+874 T/A) is the most studied polymorphism in terms of its association with TB disease sites and severity (Araujo et al, 2017;Leandro et al, 2013;Wei et al, 2017). However, to the best of our knowledge, the association between this SNP and drug resistance or drug sensitivity among TB patients has not been investigated.…”