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Know Your Genes: HLADQ “The Gluten Intolerance Gene”

Gluten Intolerance

The Human Leukocyte Antigen system (HLA) gene is associated with the synthesis of Major Histocompatibility Complex (MHC), which are cell surface proteins that are associated with the regulation of the immune system. There are six single nucleotide polymorphisms of this gene complex, HLA DQ(rs7454108), HLA DQ 2.5 (rs2187668), HLA DQ 2.2 (rs7775228, rs2395182, rs4713586) and HLA DQ7 (rs4639334) which have been shown to be associated with gluten intolerance.

Association with Gluten Intolerance:

Farming and agriculture introduced humans to new proteins about 10,000 years ago. Gluten is one such protein present in wheat, which makes bread light and springy as it traps steam and carbon-di-oxide when the dough rises during baking. However, this protein cannot be completely broken down into amino acids like other proteins are. Instead it is broken down to the peptides- gliadin and glutenin. People with certain variants of the gene have been shown to react to these peptides, giving rise to classic symptoms of gluten intolerance like diarrhea, stomach cramps, tiredness and abdominal bloating.

Celiac disease is a severe form of gluten intolerance and it is found to affect 1% of the population. Non-celiac gluten sensitivity is a mild form of gluten intolerance. In India, more than 10% of the population has gluten intolerance.

The HLA DQ genes have been shown to be strong genetic predictors of celiac disease. In a study conducted to assess the genetic predisposition to gluten intolerance, nearly all the patients with celiac disease had the risk allele in the HLA DQ2 and the HLA DQ8 gene, with the absence of these variants in 100% of people without celiac disease.
In a study conducted to analyze the human leukocyte antigen alleles, people with the G variant of HLA DQ(rs7454108), T variant of HLA DQ 2.5 (rs2187668), G variant of HLA DQ 2.2 (rs7775228), T variant of HLA DQ 2.2 (rs2395182), G variant of  HLA DQ 2.2 (rs4713586) and A variant of HLA DQ7 (rs4639334) were shown to be associated with predicting a reaction to gluten in the diet.

Genotype

   HLA DQ(rs7454108)    

Phenotype

AA
  • [Advantage] More likely to be gluten tolerant
AG
  • Moderate risk for gluten intolerance
GG

 

Genotype

HLA DQ 2.5 (rs2187668)

Phenotype

CC
  • [Advantage] More likely to be gluten tolerant
CT
  • Moderate risk for gluten intolerance
TT

 

Genotype

HLA DQ 2.2 (rs7775228)

Phenotype

AA
  • [Advantage] More likely to be gluten tolerant
AG
  • Moderate risk for gluten intolerance
GG

 

Genotype

HLA DQ 2.2 (rs4713586)

Phenotype

AA
  • [Advantage] More likely to be gluten tolerant
AG
  • Moderate risk for gluten intolerance
GG

 

Genotype

   HLA DQ7 (rs4639334)  

Phenotype

GG
  • [Advantage] More likely to be gluten tolerant
AG
  • Moderate risk for gluten intolerance
AA

How can this information be used?

It is important to choose an appropriate diet based on the genetic profile

 

For people with Risk Variant (Gluten Intolerant)

  • People with gluten intolerance should completely avoid gluten in their food. There are many gluten free products available in the market.
  • Rice is gluten free, which could be the reason behind the low prevalence of gluten intolerance among South Indians.
  • People with moderate risk should watch out for symptoms associated with gluten intolerance and avoid it from the diet, only if there are symptoms.

 

For people with Normal Variant (Gluten Tolerant)

  • Continue to include gluten in the diet as there is minimal risk associated with developing gluten intolerance.


References
:

  1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2386975/
  2. http://celiacindia.org.in/
  3. https://www.ncbi.nlm.nih.gov/pubmed/26603490
  4. https://www.ncbi.nlm.nih.gov/pubmed/27278238
  5. http://www.grupoaran.com/mrmUpdate/lecturaPDFfromXML.asp?IdArt=4621240&TO=RVN&Eng=1
  6. https://www.geneticliteracyproject.org/2015/07/14/facts-behind-celiac-disease-and-gluten-intolerance/
  7. https://www.ncbi.nlm.nih.gov/pubmed/18184122
  8. http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0002270

Related Links:

  1. https://www.xcode.in/dna-and-nutrition/over-10-indians-suffer-from-gluten-intolerance-are-you-one-of-them
  2. https://www.xcode.in/dna-and-health/world-osteoporosis-day-2016-osteoporosis-could-be-linked-to-gluten-intolerance
  3. https://www.xcode.in/product/gluten-intolerance-genetic-assessment

 

Find out which variation of the gene you carry and more at www.xcode.in

Nutrigenetics, fitness genetics, health genetics are all nascent but rapidly growing areas within human genetics. The information provided herein is based on preliminary scientific studies and it is to be read and understood in that context.”

Amrita Surendranath
Amrita Surendranath
Amrita has a Masters in Human Genetics which fuelled her passion for genes and their diktats. She loves converting genetic research into exciting scientific news with a punch. 10 years on, her interesting insights have covered a range of topics that include cancer, diabetes, nutrition, fitness and more. A pulse on what’s interesting aids in decoding laboratory data into useful science that could empower people into molding healthier lifestyles.