Genetic Risk Factors for Celiac Disease


I read with great interest the article by Dr. Rashid and colleagues,1 as it provided valuable information to oral health care providers on celiac disease (CD). The authors state that CD is hereditary and caused by an autoimmune mechanism in those who are genetically susceptible to the disease.1 In addition, they state that serologic screening is recommended for all those at high risk for the disease, such as first- and second-degree relatives of patients with CD and others with autoimmune disorders (e.g., type 1 diabetes mellitus, thyroiditis and Down syndrome).1 Finally, the authors mention that highly sensitive and specific serologic tests are available to screen for CD. The tests currently recommended are the serum immunoglobulin A (IgA) tissue transglutaminase (TTG) antibody test and the IgA-endomysial antibody (EMA) test.1

In my opinion, the authors neglected to discuss human leukocyte antigen (HLA) typing to identify specific genetic risk factors associated with CD. Two HLA molecules, specifically HLA-DQ2 and HLA-DQ8, have been identified as genetic risk factors for CD.2,3 Published reports state that 90%–95% of patients with CD carry the serologically defined HLA-DQ2 heterodimer, while the remaining 5%–10% who are HLA-DQ2-negative demonstrate an HLA-DQ8 heterodimer.3 In addition, inheritance of specific HLA alleles may influence disease phenotype and prognosis.3

Patients demonstrating homozygosity for HLA-DQ2 may be at risk for developing more severe complications related to CD.2,3 CD is highly unlikely in cases where both HLA-DQ2 and HLA-DQ8 are absent, which may assist in diagnostic evaluation for this disease.2

It should be noted that CD is a multigenic disorder with non-HLA alleles contributing genetic polymorphisms to the disease.2 Also, the practical clinical application of HLA typing has yet to be fully determined and may be most useful in screening high-risk groups for CD (as described by the authors) or cases where the diagnosis of CD remains uncertain (i.e., non-specific histologic changes demonstrated on biopsy).3 Currently, HLA typing may be considered as an adjunctive serologic test to standard TTG and EMA analysis for patients with suspected CD.3

I commend the authors on their informative manuscript regarding CD and hope this letter clarifies and elaborates on the genetic aspects of CD alluded to in the article.

Dr. Eric Stoopler
Associate professor of oral medicine
University of Pennsylvania
Philadelphia, PA


  1. Rashid M, Zarkadas M, Anca A, Limeback H. Oral manifestations of celiac disease: a clinical guide for dentists. J Can Dent Assoc. 2011;77:b39.
  2. Tack GJ, Verbeek WHM, Schreurs MWJ, Mulder CJJ. The spectrum of celiac disease: epidemiology, clinical aspects and treatment. Nat Rev Gastroenterol Hepatol. 2010;7(4):204-13.
  3. Cassinotti A, Birindelli S, Clerici M, Trabattoni D, Lazzaroni M, Ardizzone S, et al.. HLA and autoimmune digestive disease: a clinically oriented review for gastroenterologists. Am J Gastroenterol. 2009;104(1):195-217.


One of the Authors Responds

Cite this as: J Can Dent Assoc 2011;77:b112

We appreciate Dr. Stoopler's comments on our article on celiac disease (CD).1 He has highlighted an important aspect of the genetics of CD by pointing out the 2 HLA markers (HLA-DQ2 and HLA-DQ8) that have been identified as genetic risk factors for CD.

There are multiple factors involved in the pathogenesis of CD, including genes and environment. Genetics certainly plays an important role. Almost all patients with CD will be positive for HLA-DQ2 or HLA-DQ8. However, about 30% of the North American population carries one of these HLA types, of which only a very small number will ever develop CD.2 Therefore, the presence of the markers does not confirm CD, but their absence virtually rules out CD as a diagnosis. In other words, HLA-DQ2 or HLA-DQ8 testing carries a high negative predictive value for CD.

In contrast to serological testing, HLA typing is expensive and is not routinely available. At this time, it cannot be recommended as a test to screen for CD. Efforts are underway to make HLA-DQ2/DQ8 testing available on a routine commercial basis. It is likely that in the near future one may be able to order this test to identify individuals who are positive and at risk of developing CD and to reassure those who are negative. HLA testing will supplement serological testing in these clinical situations.

Perhaps we could have written more on the genetics of CD in our JCDA article, but there were space limitations. Our Introduction was kept brief and specific to the dental community so our focus was on enamel defects and oral lesions related to CD. However, there are several good review articles available in the literature on the genetic risk factors of CD.3,4

Dr. Mohsin Rashid
Associate professor of pediatrics and medical education
Dalhousie University
Halifax, NS


  1. Rashid M, Zarkadas M, Anca A, Limeback H. Oral manifestations of celiac disease: a clinical guide for dentists. J Can Dent Assoc. 2011;77:b39.
  2. Rostom A, Dube C, Cranney A, Saloojee N, Sy R, Garritty C, et al. Celiac disease. Evid Rep Technol Assess (Summ). 2004;(104):1-6.
  3. Freeman HJ, Chopra A, Clandinin MT, Thomson ABR. Recent advances in celiac disease. World J Gastroenterol. 2011;17(18):2259-72.
  4. Rostom A, Murray JA, Kagnoff MK. American Gastroenterological Association (AGA) Institute technical review on the diagnosis and management of celiac disease. Gastroenterology. 2006;131(6):1981-2002.