Mendelian Susceptibility to Mycobacterial Diseases MSMD has especially been associated with defects in the IL12B, IL12RB1, IRF8, ISG15, NEMO, IFNGR1, IFNGR2, STAT1, IRF8, and CYBB genes (15-22).
Most patients with IL12B, IL12RB1, NEMO, IFNGR1, IFNGR2 deficiencies present with mycobacterial infections and are diagnosed as a result of investigations for diseases that might cause a predisposition to mycobacterial infections.
Amplification and Sequencing of IFNGR1 Proximal Promoter PCR.
Distribution of the IFNGR1 Promoter Mutation in Different Plasma Levels of IFN-[gamma].
This study also highlights a potential therapeutic role of TH and MH to modulate haematological parameters and the expression of Apaf-1, Caspase-9, IFN-[gamma], IFNGR1, p53, E2, ESR1, TNF-[alpha], COX-2, and Bcl-xL in in vivo breast cancer model.
Immunohistochemical Analysis for Apaf-1, Caspase-9, p53, FASLG, FADD, IFNGR1, TNF-[alpha], COX-2, ESR1, and Bcl-xl in Breast Cancer Masses.
Variants in IFNGR1 often result in susceptibility to environmental mycobacteria (e.g., Mycobacterium avium; immunodeficiency 27a), M.
It is, therefore, perhaps not surprising that the receptor gene IFNGR1 is also highly conserved, illustrated by the fact that only one missense polymorphism (defined as having a frequency >1% worldwide; p.Leu467Pro; frequency 5%) was found by the Exome Aggregation Consortium (ExAC) in 60,706 unrelated individuals .
The investigated target genes were IL10, IL10RA, IL10RB, JAK1, STAT3, SOCS3, IP10, ICAM1, IFNA, IFNARA, IFNAR2, IFNG, IFNGR1
, IFNGR2, STAT1, and IRF1.
The central players of IFN[gamma] signaling via the classical or canonical pathway involve the IFN[gamma], receptor subunits IFNGR1
and IFNGR2, tyrosine kinases JAK1 and JAK2, and STATla transcription factor [1-4].
Downregulation of IFN-[gamma] receptor occurs due to type I IFN-mediated recruitment of transcriptional regulators, early growth response factor 3 (Egr3), and NGFI-A binding protein 1 (Nab1), to the ifngr1
promoter and subsequent gene silencing .
In contrast, mRNA levels of interferon gamma receptor 1 (IFNGR1
), activin A receptor, type 1 (ACVR1), and activated leukocyte cell adhesion molecule (ALCAM) all exhibited downregulation in study subjects of the high-level arsenic exposure group.