From the Guidelines
Testing for celiac genes is recommended if celiac testing is negative, as a negative genetic test can effectively rule out celiac disease, especially if you still have symptoms suggestive of the condition. The genetic test looks for HLA-DQ2 and HLA-DQ8 genes, which are present in about 95% of people with celiac disease 1. A negative genetic test can effectively rule out celiac disease, as it's very unlikely to have the condition without these genes. However, having these genes doesn't mean you have celiac disease—about 30-40% of the general population carries them but only about 1% develops the condition. Consider genetic testing if you've already started a gluten-free diet (which can affect standard celiac tests), have a family history of celiac disease, or have persistent symptoms despite negative antibody tests.
Some key points to consider:
- HLA-DQ2 and HLA-DQ8 genes are strongly associated with celiac disease, and their absence can help rule out the condition 1.
- Genetic testing may be useful in select patients, such as those with Down syndrome, equivocal small-bowel histologic findings, or those following a gluten-free diet without prior testing for celiac disease 1.
- A negative result for HLA DQ2 and DQ8 can confirm that celiac disease is not present, and prevent unnecessary further diagnostic workup or gluten challenge 1.
- It's essential to carefully interpret genetic test results, considering all possible alleles associated with celiac disease, and to discuss the results with a healthcare provider to determine the best course of action 1.
In terms of specific scenarios where genetic testing may be beneficial, consider the following:
- If you've already started a gluten-free diet and have persistent symptoms, genetic testing can help determine if celiac disease is still a possibility 1.
- If you have a family history of celiac disease and negative antibody tests, genetic testing can help assess your risk of developing the condition 1.
- If you have symptoms suggestive of celiac disease but negative celiac testing, genetic testing can help rule out the condition or identify potential genetic risk factors 1.
Ultimately, genetic testing for celiac disease should be considered on a case-by-case basis, taking into account individual symptoms, medical history, and previous test results, and in consultation with a healthcare provider 1.
From the Research
Celiac Disease and HLA Genetic Testing
- Celiac disease is a common inflammatory disease triggered by dietary gluten in genetically susceptible individuals, with the strongest genetic susceptibilities being class II human leukocyte antigen (HLA) genes known as HLA-DQ2 and DQ8 2.
- HLA genetic testing has a high negative predictive value for celiac disease, but a low positive predictive value, making it useful for ruling out the disease in at-risk populations 3, 4.
Testing for Celiac Gene when Celiac Testing is Negative
- A negative HLA result usually obviates the need for further celiac testing, including endoscopy and gluten challenge 3.
- However, rare cases of celiac disease have been reported in individuals with negative HLA testing, highlighting the importance of considering other diagnostic criteria 3.
- The presence of HLA-DQ2 and/or DQ8 is not sufficient to diagnose celiac disease, and other factors such as clinical symptoms, intestinal biopsy, and antibody testing should also be considered 5, 6, 4.
Clinical Utility of HLA Testing
- HLA testing can be a valuable tool in the diagnosis of celiac disease, particularly in patients with inconclusive initial evaluations 3.
- The diagnostic yield of HLA testing varies widely depending on the clinical indication, with highest yields in patients with intraepithelial lymphocytosis and normal IgA tissue transglutaminase antibody 3.
- DQ2/DQ8 typing is an effective test to exclude celiac disease from the differential diagnosis of a patient with celiac symptoms 6.