What are Susceptibility Genes?

Susceptibility Genes
TSG101 and PEG10 expression in AC using EnVision immunohistochemistry; original magnification, ×200. TSG101- and PEG10-positive reactions were mainly localized in the cytoplasm. (A) Positive TSG101 expression (>25% positive cells) in poorly-differentiated AC. (B) Negative TSG101 expression (<25% positive cells) in well-differentiated AC. (C) Positive PEG10 expression in poorly-differentiated AC. (D) Negative PEG10 expression in well-differentiated AC. TSG101, tumor susceptibility gene 101; PEG10, paternally expressed gene 10; AC, adenocarcinoma.TSG101 and PEG10 are prognostic markers in squamous cell/adenosquamous carcinomas and adenocarcinoma of the gallbladder. Liu Z, Yang Z, Liu D, Li D, Zou Q, Yuan Y, Li J, Liang L, Chen M, Chen S - Oncology letters (2014). Not Altered. CC.

Susceptibility genes or genetic predisposition is an increased likelihood of developing a particular disease based on a person’s genetic makeup.

Examples of susceptibility genes include:

  • HLA genes (HLA-B27)
  • Non-MHC genes
  • PTPN22
  • NOD2
  • NLR

Genetic issues that may lead to autoimmunity:

HLA-B27, also known as human leukocyte antigen B27, is a protein found on the surface of white blood cells that aids the body’s immune system in distinguishing between its own cells and foreign substances. It is found in people who have autoimmune disorder such as arthritis.

PTPN22 polymorphisms or the protein tyrosine phosphatase non-receptor type 22, is a missense polymorphism that inhibits spontaneous T-cell activation and development, as well as inactivating T-cell receptor-associated kinases and their substrates.

NOD2 polymorphism is a substitution mutation (Arginine – Glycine), or a frameshift mutation, resulting to a diminished function of its ability to detect bacteria and trigger immune response.

IL-2 polymorphisms is a single nucleotide polymorphism that affects its regulatory function in the immune system.

CD25 mutation is due to an insertion and substitution in the gene leading to the formation of a stop codon which terminates its regulation and activity in the immune system

AIRE mutation causes autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). This causation is due to the missense mutation of the gene that shortens it and makes it inactive compromising its role as an autoimmune regulator and a central contributor to central tolerance.

CTLA4 mutation occurs as a heterozygous nonsense mutation, gene splicing, or missense mutation that decreases the expression of CTLA4 protein which is responsible for the negative regulation of immunity.

PD1 mutation negates the suppressive effect of the gene on T-cell acivation

FAS mutation leads to the accumulation of lymphocytes after an immune response is triggered due to the interference to the initiation of apoptosis

FASL mutation in the exon site causes defect in apoptosis function resulting to autoimmune lymphoproliferative syndrome

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Last updated on May 27, 2022