Edited: This was originally posted as two entries, now combined to have all the information in one spot.
One of my main reasons for getting 23andMe testing done was to figure out if I could possibly have celiac disease. I went gluten-free about five years ago and have felt so much better that I didn’t want to go back to eating gluten in order to get the testing done for celiac. You see, the ‘Catch-22’ of getting diagnosed for celiac disease is that you have to be eating gluten for a while before getting tested. So I was hoping that the genetic testing would rule out the possibility of celiac for me (and my family).
First a little background information...
Celiac disease (spelled coeliac in Britain) is an autoimmune disorder in which gluten causes damage to the villi in the small intestines. Gluten is a protein found in wheat, barley, rye, and spelt. There are many resources on the internet with great information about celiac disease and the symptoms involved. Celiac.org is a good starting point for anyone wanting to learn more.
Genetic component to Celiac…
There isn’t one gene polymorphism that causes everyone who has it to get celiac disease, but there are polymorphisms that must be present in order for a person to be susceptible to celiac disease. So if the polymorphism isn’t present, you can nearly always rule out the disease.
Virtually everyone with celiac disease has either the HLA-DQ2 or HLA-DQ8 alleles. Specifically, 90-95% of people with celiac disease have HLA-DQ2.5, and 5 – 10% of people have HLA DQ8. (Some studies also list HLA 2.2 as a possibility for celiac as well.) Almost 25% of the population has HLA-DQ2.5, and that percentage grows to about 30% when adding in HLA DQ8. [ref] There are a couple of single nucleotide polymorphisms (SNPs) that you can look at (listed below) to determine if you have those HLA types. With only about 1% of the population having celiac disease, you can see that just having the HLA type doesn’t mean that you will get celiac disease.
So looking at your genetic polymorphisms could help you rule out celiac disease, but not tell you if you have it.
***This information all comes with the disclaimer that you should always talk with your doctor for a diagnosis. Seriously! Your doctor can order tests such as blood test or a small intestine biopsy to accurately diagnose or rule out celiac disease.***
A little science background…
So what is an HLA serotype? Serotypes, discovered in 1933 by Rebecca Lancefield, are variations within species (bacteria and viruses) or among immune cells of people. The typing is based on their cell surface antigens. In humans, the human leukocyte antigen (HLA) determines the serotype; the HLA serotype is sometimes used in determining transplant matches.
One HLA type is HLA-DQ, which is a protein found on antigen presenting cells. DQ is involved in the immune system through stimulating T-cells which then signal B-cells to produce antibodies. The HLA-DQ recognizes foreign antigens from pathogens, but it also recognizes common self-antigens. This is where the problem begins when the HLA-DQ loses it tolerance to self-proteins, triggering autoimmune diseases such as celiac, lupus, and type 1 diabetes.
SNP’s involved in Celiac:
Approximately 90-95% of celiac patients have HLA-DQ2.5, which can be determined from the SNP rs2187668 (T). [ref] The SNP is fairly common and found in about 25% of European caucasians. So, again, having the SNP does not mean that you have Celiac, only that it is possible for you to have it or develop it at some point.
|Check your 23andMe results for rs2187668:
HLA-DQ8 alone is found in about 5-10% percentage of Celiac patients.
|Check your 23andMe results for rs7454108:
The SNPs above cover most people with celiac, but not quite all. The HLA-DQ2.2 variant, found by itself in a very small percentage of celiac cases, can not be completely determined with the current version of 23andMe data.
Other genes involved in celiac….
Since about 1% of those with European ancestry receive a diagnosis of celiac while 30% have the HLA types for it, something else must also be involved in a person’s risk for celiac. Recent studies have looked into other genetic traits, as well as environmental aspects such as duration of breastfeeding, timing of the introduction of wheat to an infant’s diet, and types of bacteria in the gut.
Below are a few of the current studies on possible genetic causes of celiac disease.
A large 2011 study looked at genetic differences between over 12,000 individuals with celiac compared to approximately the same number without celiac disease. This study identified quite a few polymorphisms that influence the risk of celiac disease. Look at Table 2 in the study to see the SNPs and their risk.
A sibling study from 2011 found three SNPs to be significant in increasing the risk of celiac disease among siblings where one sibling had been diagnosed with celiac. The A-alleles of rs1464510, rs842647, and rs2816316 increased the risk of celiac disease in siblings in conjunction with the HLA type. See Table 2 in the study.
|Check your 23andMe results for rs1464510:
|Check your 23andMe results for rs842647:
|Check your 23andMe results for rs2816316:
An August 2015 meta analysis showed that a T-allele (23andMe orientation) on rs917997 increased the risk of celiac disease by 5%, The same study showed that a T-allele on rs6441961 increased the risk of celiac by 6%.
|Check your 23andMe results for rs917997:
|Check your 23andMe results for rs6441961:
A Finish study from 2012 found that FUT2 non-secretors are at an increased risk of celiac disease. The AA genotype for rs601338 determines a non-secretor. The odds ratio for non-secretors for celiac is 1.28. (Non-secretors are also resistant to the Norovirus.)
|Check your 23andMe results for rs601338:
It seems that there is quite a bit of research going on right now into why one person with HLA DQ2.5 will have celiac disease while another won’t ever get it. For anyone who is interested in further researching the topic, a PubMed search of “Celiac polymorphism” currently returns over 1800 results. One other aspect that has recently been studied is the effect of the gut microbiome. A 2015 paper in the journal, Nutrients, summed up the current research into the gut microbe connection. Another 2015 article in the American Journal of Pathology is worth reading and tantalizing. It is exciting to see how close we are to finally understanding this disease.