Celiac Genes
Celiac disease is intolerance to gluten that affects the small intestinal lining when foods containing gluten are in included in the diet1.
People with celiac feel abdomen pain, bloating, diarrhea, fatigue, and mouth sores2. If continued, they have may suffer from weight loss, lower bone mineral density, iron and vitamin D deficiency, and short stature.
When gluten comes into contact with the lining of small intestine, it causes inflammation and damages the surface. This damage of the surface causes low fluid secretion to digest the food resulting in mal-absorption and eventual destruction of this intestinal lining.
The actual problem3 starts with high proline—large chunks of certain proteins in some foods—mainly wheat, barley, and rye, that are harder to digest and break down in the intestine.
An enzyme called tissue trans-glut-aminase converts these undigested protein fragments into a form that binds to certain antibodies.
The DQ2, DQ8 genes4 produce these antibodies that bind with the gluten peptide molecules. Therefore, these antibody producing genes are necessary to cause gluten intolerance.
Although essential, presence of these genes is not a guarantee of testing positive for celiac—reasons for that are not yet understood.
The gluten from diet binds to the cells through a dimer—a two-armed molecule5 with alpha and beta chains that are formed by the specific genes inside the cells. Both arms might be made from the genes inherited from either parent or both parents.
That’s is the reason why celiac runs within families. About 50% of first relatives to those with the DQ2 or DQ8 genes might be affected.
Although about 1% of population in US and Europe likely has celiac, almost 5-15% of family members show gluten sensitivity in affected families.
Studies of identical twins6 show that in 70-75% cases, both were affected if one of them had celiac. That’s more than auto-immune diseases7 of Type 1 diabetes (36%), Crohn's disease (33%), and multiple sclerosis (25%).
Almost 90-95% or more celiac positive cases carry DQ2. In 5-10% cases, they also carry DQ8. This combination of DQ2 and DQ8 covers almost 100% of patients.
It is extremely rare to find celiac disease (0.04%) in people who do not have the relevant genes. Therefore, a negative result is extremely valuable.
Certain genes are dominant. For example, a higher chance of DQ2 genes in the overall DQ system increases the chances of celiac. Studies show that only about 2% positive cases have DQB1 genes—the one forming beta chain of dimer—but they may be almost 25% of known celiac cases.
In general, almost 40% of the western population has DQ2 or DQ8 genes but only about 1% are celiac positive. Over 39 genes8 now relate to celiac disease but most have much lower correlation.
In 2012, the New England Journal of Medicine suggested9, "testing for HLA-DQ2 and HLA-DQ8 may be useful in at-risk persons (e.g., family members of a patient with celiac disease)". Such testing has a "high-negative predictive value, which means that the disease is very unlikely to develop in persons who are negative for both HLA-DQ2 and HLA-DQ8". In fact, "Up to 97% of cases", the HLA phenotypes are prerequisite for celiac.
A 2019 Mayo Clinic study10 had similar conclusion calling for screening of family members.
We cannot control our genes, but with a few simple steps we can test to learn if we have inherited them.
