HLADQ Gene: Gluten Sensitivity From 23andme Ancestry DNA Raw Data

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.

Does your 23andme, Ancestry DNA, FTDNA raw data have HLA DQ gene variant information?

CHIP Version	HLA DQ SNPs
23andMe (Use your 23andme raw data to know your HLA DQ Variant)
v1 23andme	Present
v2 23andme	Present
v3 23andme	Present
v4 23andme	Present
V5 23andme (current chip)	Present
AncestryDNA (Use your ancestry DNA raw data to know your HLA DQ Variant)
v1 ancestry DNA	Present
V2 ancestry DNA (current chip)	Present
Family Tree DNA (Use your FTDNA raw data to know your HLA DQ Variant)
OmniExpress microarray chip	Present

Genotype HLA DQ(rs7454108)	Phenotype
AA	[Advantage] More likely to be gluten tolerant
AG	Moderate risk for gluten intolerance
GG	[Limitation] More likely to be gluten intolerant

Genotype HLA DQ 2.5 (rs2187668)	Phenotype
CC	[Advantage] More likely to be gluten tolerant
CT	Moderate risk for gluten intolerance
TT	[Limitation] More likely to be gluten intolerant

Genotype HLA DQ 2.2 (rs7775228)	Phenotype
AA	[Advantage] More likely to be gluten tolerant
AG	Moderate risk for gluten intolerance
GG	[Limitation] More likely to be gluten intolerant

Genotype HLA DQ 2.2 (rs4713586)	Phenotype
AA	[Advantage] More likely to be gluten tolerant
AG	Moderate risk for gluten intolerance
GG	[Limitation] More likely to be gluten intolerant

Genotype HLA DQ7 (rs4639334)	Phenotype
GG	[Advantage] More likely to be gluten tolerant
AG	Moderate risk for gluten intolerance
AA	[Limitation] More likely to be gluten intolerant

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.

Know Your Genes: HLADQ “The Gluten Intolerance Gene”

Association with Gluten Intolerance:

Does your 23andme, Ancestry DNA, FTDNA raw data have HLA DQ gene variant information?

References:

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