What is Celiac? Past, Present and Genetic Risk

What is Celiac? Past, Present and Genetic Risk

Created On
Dec 07 2020
Last Updated
Jul 19 2022

Despite affecting almost 1% of population (i.e., over 3 million in US alone), very few individuals diagnose for celiac (coeliac) disease.

That’s mainly because the symptoms of gluten intolerance vary significantly, from no signs for years to immediate reactions of rashes, vomiting, diarrhea, and abdominal pain.

How Common is Celiac Disease?

Celiac is compared to an iceberg–only the tip is visible–majority of cases are hidden and undiagnosed. Few studies that tried to quantify the regional occurrence of celiac in various geographical regions include:

  1. An Italian study found 1 in 184 students as celiac positive–and 6 out of 7 were previously undiagnosed. Of these 17,000 middle school students, found 7.5% (or 1289) were positive for the initial IgA, IgG blood test and 0.5% (or 82) were positive for celiac.

  2. A Swedish study of approx. 1900 adults showed 1 in 254 had celiac disease.

  3. In a US study 1 in 250 people were positive for celiac.

  4. An Irish study found a higher ratio of 1 in 122 people with celiac, although with a relatively smaller dataset.

  5. Study of 2500 healthy individuals in Tunisia, in North Africa, found 1 in 355 had celiac disease.

  6. The highest ever occurrence of 5.7% was reported in Algeria among the Saharawi tribes of Sahara desert. They have a high frequency of DQ2 genes and recently changed their dietary habits due to the war.

  7. A review of non-western countries have identified celiac across Africa, India, East Asia, Latin America, Middle East, South America, and Australia.


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History of Celiac

  • First described in Greece during second century AD by Aretaeus of Cappadocia.

  • In 1786 William Buchanan of Edinburgh and in 1888, Samuel Gee of St. Bartholomew’s Hospital in London described the modern day celiac symptoms.

  • Sydney Hass, in 1924, demonstrated success in treating children with a banana-rich diet that excluded bread and sugar.

  • During World War II, Dutch pediatrician WK Dicke and his colleagues connected wheat to celiac. The health of children improved dramatically when wheat, barley, and rye were in short supply but symptoms returned after the war.

  • In 1954, Dr Paulley was the first physician to appreciate the role of biopsy in celiac diagnosis.

  • Falchuk in 1972 confirmed the genetic association of celiac to a particular gene. Subsequently, several groups in 1980s conclusively connect DQ2 genes (or DQ8 in small cases) to all celiac patients; Sollid (in 1989) specifically points out the association of celiac with DQ haplotypes.

  • In 1998, Dietrich in Berlin and Sulkanen in Finland developed today’s highly sensitive tTG antibody celiac test.


What Causes Gluten Intolerance?

Celiac is activated in genetically susceptible individuals by the ingestion of gluten.

The response is due to two specific amino acids called proline and glutamine that are found in wheat, rye, and barley. Broadly speaking, many celiac disease-activating proteins are called “gluten”. However, strictly speaking gluten is the scientific name for the disease-activating proteins only in wheat.

Gluten in wheat has two major protein fractions called gliadins and glutenins, both of which contain the celiac-activating proteins. The closely related proteins in barley and rye are hordeins and secalins, respectively. Wheat, rye, and barley are related in their origin.

Oats is more distantly related and the equivalent proteins, called avenins, are extremely rare to cause celiac, especially in moderation.

Rice, corn, sorghum, Job’s tears, millet, and tef are even more distantly related and not known to cause celiac.  

Why gluten even matters?

It’s not the gluten, it’s the excess proline content in wheat, rye, and barley that makes the body hard to digest it.

One theory is that large chunks of proteins inside the smaller intestine remain without full digestion and break down into smaller peptide ingredients. These undigested peptides cross the intestinal lining where they find the appropriate pathways to react.

An enzyme called trans-glutaminase will ionize the proline and glutamine.

What is the path to gluten sensitivity?

  • High proline content in wheat, barley, and rye make it harder to digest and break down in the intestine.

  • The tissue trans-glut-aminase enzyme converts the undigested protein into a form that binds to the antibodies

  • The DQ2, DQ8 genes produce antibodies that bind with the gluten peptide molecules


Is Gluten Intolerance or Celiac Disease a Genetic Condition?

Almost 50% of first relatives are affected and a genetic test for DQ2 or DQ8 genes can help assess their risk. These genes are required for developing gluten intolerance, although not everyone testing positive may have celiac.

Historic signs of genetic pre-disposition to celiac

  • Although about 1% of the population has celiac, almost 5-15% of family members show gluten intolerance in affected families.

  • In 70-75% of identical twins, both were affected if one of them had celiac (e.g., in a Spanish study). This is much higher than other auto-immune diseases of Type 1 diabetes (36%), Crohn’s disease (33%), and multiple sclerosis (25%).

  • Almost 90-95% or more patients carry DQ2.

  • 5-10% also carry DQ8.

  • Combined DQ2 and DQ8 are present in almost 100% of patients.

  • Higher the DQ2 molecules in the DQ system, higher the chances of celiac; only about 2% has DQB1 genes, they may be almost 25% of known celiac cases.

  • Almost 40% of the western population has DQ2 or DQ8 genes but only about 1% have celiac.

  • Over 39 genes now relate to celiac disease but most have much lower correlation.

  • Celiac is rare in Japan where the DQ alleles are also rare (only two cases as of 2006).

How do genes contribute to celiac disease?

The antigens produced by the DQ2 or DQ8 genes bind with the gluten. The body’s defensive T-cells than recognize these bound antigens. Before binding, however, the gluten requires an enzyme called trans-glutanase to convert to a DQ2 or DQ8 friendly form.

The antibodies this enzyme produces are the markers for IgA test to diagnose celiac disease.

The DQ2 and DQ8 genes account for approximately 40% of the genetic risk. Thus far, the search for the other associated genes has identified a total of 39 genes. But most have much lower risks than the DQ genes.

A standard diagnosis includes testing for IgA antibodies developed in the body against an enzyme called trans-glut-aminase (tTG) responsible for binding with gluten.

Those testing positive will likely have intestinal walls damaged and should be confirmed with a biopsy.

One challenge for IgA-tTG test is that approx. 2.6% celiac patients have 10-15 times higher deficiency for the IgA antibodies.

A very small group only develops IgG antibodies. The IgG test is highly specific and helps avoid any false negatives. These deficient groups might be difficult to diagnose.

There is no known cure for celiac. A lifelong adherence to gluten-free diet is the only therapy as of 2019.