What is the Celiac Disease Genotyping Test?
The celiac disease genotyping test will determine if you carry one or more of the alleles (HLA-DQA1*05, HLA-DQB1*02, HLA-DQB1*0302) associated with an increased risk of developing celiac disease. It is important to note that individuals who test positive for one or more of these alleles are at an increased risk, but not all individuals who carry these alleles will develop celiac disease. However, this genotyping analysis is very useful to exclude a possible celiac diagnosis if none of these alleles are detected, as there is a less than 0.04% chance of developing celiac disease in people that don’t have one or more of these at-risk alleles.
What are the HLA-DQA1 and HLA-DQB1 Genes?
There are more than 200 HLA genes, which are located on chromosome 6 and encode components of the human leukocyte antigen (HLA) complex. The HLA complex is an important part of the immune system, helping distinguish between harmless proteins (from self, diet or environment) and harmful foreign proteins from viruses and bacteria. The protein encoded by the HLA-DQA1 and HLA-DQB1 genes form a complex together to display foreign proteins to the immune system in order to trigger a response against the foreign invader. This HLA-DQA1 + HLA-DQB1 complex is also important to develop self-tolerance in children. However, in celiac-affected people, this complex also binds to and displays the harmless gliadin fraction from gluten, initiating an aberrant immune response.
Variation in the HLA-DQA1 and HLA-DQB1 Genes
HLA genes vary significantly between individuals and several hundred different versions (or alleles) of the HLA-DQA1 and HLA-DQB1 genes have been identified. Each allele is allocated a particular number and specific HLA alleles are associated with various health conditions. The majority (90-95%) of celiac-affected individuals carry the DQ2 heterodimer, which is complex formed from HLA-DQA1*05 and HLA-DQB1*02. 5-10% of celiac-affected individuals carry the DQ8 heterodimer, which is a complex formed from HLA-DQB1*03.02 and HLA-DQA1*03. These complexes recognize the gliadin fraction from gluten and display this foreign protein to the immune system, initiating an immune response.
Patients that have the high-risk HLA-DQB1*02 allele and also have the high-risk HLA-DQA1*05 allele have the DQ2 haplotype (or more specifically the DQ2.5 haplotype) and are at the greatest risk of developing celiac disease and experiencing severe complications.
The high-risk HLA-DQB1*0302 allele is always inherited with one of the HLA-DQA1*03 alleles due to linkage disequilibrium and this produces the DQ8 haplotype. Those with the DQ8 haplotype have an increased risk of celiac disease but the risk is not as high as those that carry the DQ2 haplotype.
Celiac Disease Genotyping Test Specifications
None. This test can be taken at any age.
Buccal swabs. The test kit contains buccal swabs and instructions for collecting a buccal swab sample from inside the mouth.
Four buccal swabs, rubbed inside the mouth against the cheek for 15 seconds.
1 – 2 weeks.
Sequence Based Typing (SBT)
DNA test kits do not have an expiry date and can be used at any time. Once the DNA sample is collected, it must be returned to the laboratory for testing within three months of collection. No refrigeration is required. Store at room temperature.
It is important to remember that the presence of one or more of these at-risk alleles (HLA-DQA1*05, HLA-DQB1*02, HLA-DQB1*0302) does not mean that an individual will definitely develop celiac disease. Each allele does increase the risk but there are many individuals that have these alleles and never develop celiac disease. Alleles other that HLA-DQA1*05, HLA-DQB1*02 and HLA-DQB1*0302 will not be identified. An increased risk of celiac disease and an accurate diagnosis are also dependent on a variety of genetic and non-genetic factors that are not detected by this assay.
Next, Understanding Your Celiac Disease DNA Test Results »
Liu E et al. (2014). Risk of Pediatric Celiac Disease According to HLA Haplotype and Country. N Engl J Med. 371: 42-49.
Megiorni F, Mora B, Bonamico M, Barbato M, Nenna R, Maiella G, Mazzilli MC (2009). HLA-DQ and risk gradient for celiac disease. Hum Immunol 70(1): 55-59.
Pietzak MM, Schofield TC, McGinniss MJ, Nakamura RM (2009).Stratifying risk for celiac disease in a large at-risk United States population by using HLA alleles. Clin Gastroenterol Hepatol. 7(9): 966-71.