Celiac disease is a systemic immune disease which causes inflammation of the small bowel and villous damage when a genetically susceptible individual ingests gluten. Over 95% of individuals with celiac disease have specific celiac disease-associated alleles in the HLA-DQA1 and HLA-DQB1 genes (HLA-DQA1*05, HLA-DQB1*02 and HLA-DQB1*0302).
The presence of celiac disease-associated HLA alleles implies an increased risk for celiac disease, but is not diagnostic of celiac disease as only a subset of individuals with these alleles will develop celiac disease. However, individuals who test negative for the celiac disease-associated alleles HLA-DQA1*05, HLA-DQB1*02 and HLA-DQB1*0302 can essentially exclude a diagnosis of celiac disease and have almost no lifetime risk of developing celiac disease (less than 0.04% chance), regardless of whether or not they ingest gluten.
The celiac disease-associated alleles HLA-DQA1*05, HLA-DQB1*02 and HLA-DQB1*0302 and the heterodimers formed by pairs of these alleles, DQ2 (encoded by HLA-DQA1*05 and HLA-DQB1*02) and/or DQ8 (encoded by HLA-DQA1*03 and HLA-DQB1*0302) can be detected through the celiac disease DNA test.
Summary of Possible Genotypes
Negative, no celiac disease-associated alleles detected
If an individual has tested negative for all of the celiac disease-associated alleles (HLA-DQA1*05, HLA-DQB1*02 and HLA-DQB1*0302), then a diagnosis of celiac disease can essentially be excluded. An absence of celiac disease-associated alleles reduces the lifetime risk of developing celiac disease to well below 0.04%, independent of diet. Individuals who test negative for celiac disease-associated alleles will not pass a celiac disease-associated allele to the next generation.
Positive, celiac disease-associated alleles detected
If an individual has tested positive for one or more than one copies of the celiac disease-associated alleles HLA-DQA1*05, HLA-DQB1*02 and HLA-DQB1*0302, then a diagnosis of celiac disease cannot be ruled out. Relatives of individuals who have tested positive for one or more celiac disease-associated alleles are also at risk for being positive. The presence of the celiac disease-associated alleles implies an increased risk for celiac disease, but is not diagnostic of celiac disease as only a subset of individuals with these alleles will develop celiac disease. The estimated risk for developing celiac disease for each genotype is listed in the table below:
PATIENT GENOTYPE (CELIAC DISEASE-ASSOCIATED ALLELES) |
CELIAC DISEASE RISK* |
|---|---|
| DQ2 and DQ8 | 1:7 |
| DQ2 and Homozygous HLA-DQB1*02 | 1:10 |
| DQ2 and DQ2 | 1:10 |
| DQ8 and DQ8 | 1:12 |
| DQ8 and HLA-DQB1*02 | 1:24 |
| Homozygous HLA-DQB1*02 | 1:26 |
| DQ2 | 1:35 |
| DQ8 | 1:89 |
| Heterozygous HLA-DQB1*02 | 1:210 |
| HLA-DQA1*05 | 1:1842 |
| No HLA celiac disease-associated alleles detected | Not at risk of developing celiac disease, less than 1:2518 |
