What genetic mutations are commonly associated with anaphylaxis?

From the Guidelines

Genetic mutations in the KIT gene, particularly the D816V mutation, as well as mutations in the TPSAB1 gene causing hereditary alpha-tryptasemia, are commonly associated with anaphylaxis, as they affect mast cell function and regulation. Several other genetic factors have been implicated in anaphylaxis risk, including mutations in the MRGPRX2 gene, which affects mast cell activation, and variants in the IL4, IL13, and IL4RA genes that regulate IgE production 1. Additionally, mutations in the FCER1A gene, which encodes the high-affinity IgE receptor, can increase susceptibility to severe allergic reactions, while mutations in the SERPING1 gene (causing hereditary angioedema) and carboxypeptidase A3 (CPA3) gene can contribute to anaphylactic reactions 1.

Some key points to consider when evaluating the genetic basis of anaphylaxis include:

• The role of mast cell function and regulation in anaphylaxis, with genetic mutations affecting these processes being particularly relevant 1
• The importance of considering multiple genetic factors, as anaphylaxis is a complex condition with multiple potential causes 1
• The need for personalized approaches to anaphylaxis prevention and management, taking into account an individual's specific genetic profile and risk factors 1

In terms of specific genetic mutations, the KIT gene D816V mutation is a well-established risk factor for anaphylaxis, particularly in the context of mastocytosis 1. Hereditary alpha-tryptasemia, caused by mutations in the TPSAB1 gene, is another condition that can increase the risk of anaphylaxis 1. Other genetic factors, such as variants in the IL4, IL13, and IL4RA genes, may also play a role in anaphylaxis risk, although the evidence for these associations is less clear 1.

Overall, a comprehensive understanding of the genetic basis of anaphylaxis is essential for developing effective prevention and management strategies, and further research is needed to fully elucidate the relationships between genetic mutations and anaphylaxis risk 1.

From the Research

Genetic Mutations Associated with Anaphylaxis

• Hereditary angioedema (HAE) is a disorder caused by a mutation in the C1 esterase inhibitor gene, specifically the SERPING1 gene, which encodes C1-INH 2, 3, 4, 5, 6
• The most common types of HAE are type I and type II, resulting from a mutation in the SERPING1 gene, with type I characterized by a deficiency in C1-INH 2, 3, 4, 6
• Other genetic mutations associated with HAE include:
  • Kininogen-1 (KNG1) 2, 5
  • Plasminogen gene (PLG) 2, 5
  • Myoferlin gene mutation (MYOF) 2, 5
  • Heparan sulfate-glucosamine 3-sulfotransferase 6 (HS3ST6) 2, 5
  • Mutation in Hageman factor (factor XII) 2, 5
  • Angiopoietin-1 (ANGPT1) 2, 5
• These mutations can lead to abnormal levels of C1-INH and high levels of bradykinin, resulting in clinical presentations such as nonpitting angioedema and abdominal pain 2, 3, 4