The Gluten Gene: Unlocking the Understanding of Gluten Sensitivity and Intolerance

Abstract

Wheat flour is one of the most important food ingredients containing several essential nutrients including proteins. Gluten is one of the major protein components of wheat consisted of glutenin (encoded on chromosome 1) and gliadin (encoded on chromosome 1 and 6) and there are around hundred genes encoding it in wheat. Gluten proteins have the ability of eliciting the pathogenic immune responses and hypersensitivity reactions in susceptible individuals called “gluten-related disorders (GRDs)”, which include celiac disease (CD), wheat allergy (WA), and non-celiac gluten sensitivity (NCGS). Currently removing gluten from the diet is the only effective treatment for mentioned GRDs and studies for the appropriate and alternative therapeutic approaches are ongoing. Accordingly, several genetic studies have focused on breeding wheat with low immunological properties through gene editing methods. The present review considers genetic characteristics of gluten protein components, focusing on their role in the incidence of gluten-related diseases, and genetic modifications conducted to produce wheat with less immunological properties.

Keywords:

• gliadin
• glutenin
• genetic loci
• wheat allergy
• celiac disease
• non-celiac gluten sensitivity

Abbreviations

ATIs, Alpha-amylase/Trypsin Inhibitors; CD, Celiac Disease; CRISPR, Clustered Regularly Interspersed Short Palindromic Repeats; DH, Dermatitis herpetiformis; ETG, Epidermal Transglutaminase; FABP2, Fatty Acid-Binding Protein 2; FODMAPs, Fermentable Oligosaccharides, Disaccharides, Monosaccharides, and Polyols; g, Gram; GWASs, Genome-Wide Association Studies; HMW, High Molecular Weight; IELs, Intraepithelial Lymphocytes; IgE, Immunoglobulin E; IL, Interleukin; kDa, Kilodalton; LMW, Low Molecular Weight; NCGS, Non-Celiac Gluten Sensitivity; P, Proline; PAF, Platelet Activator Factor; PAT, Phosphinothricin Acetyltransferase; PI, Isoelectric Point; Q, Qlutamine; RNAi, RNA interference; sgRNA, single guide RNA; SR-GS, Self-Reported Gluten Sensitive; TALENs, Transcription Activator-Like Effectors Nucleases; Th2, T helper type 2; tTG, Tissue Transglutaminase; WA, Wheat Allergy; WDEIA, Wheat-Dependent Exercise-Induced Anaphylaxis; ZFNs, Zinc-Finger Nucleases.

Author Contributions

All authors made a significant contribution to the work reported in all of the following areas: took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

Dr Robert P Anderson reports personal fees from consultancies for GSK (Wilmington, DE, USA; since 2019), Allero Therapeutics BV (Rotterdam, Netherlands; since 2020), Takeda Pharmaceutical Company Ltd/Millennium Pharmaceuticals (Cambridge MA USA; since 2019), Kanyos Bio Inc (Cambridge MA USA; since 2019), Atheneum Partners GmbH (Berlin, Germany; since 2019), being an ImmusanT Inc, CSO, employee until September 2019, principal and founder of Specific Pharma Consulting, and founder and part-owner of Novoviah Pharmaceuticals Pty Ltd, outside the submitted work; in addition, Dr Robert P Anderson has multiple patents licensed to ImmusanT (patents lodged from 2009 to 2019 relating diagnosis, and treatment of coeliac disease) and BTG International (patents lodged from 2009 to 2019 relating diagnosis, treatment, and modification of gluten for coeliac disease). The authors declare that they have no other potential conflicts of interest for this work.

Additional information

Funding

There is no funding to report.