HLA DQ Gene Dosage and Risk and Severity of Celiac Disease

Joseph A. Murray, S. Breanndan Moore, Carol T. van Dyke, Brian D. Lahr, Ross A. Dierkhising, Alan R. Zinsmeister, L. Joseph Melton, Cynthia M. Kroning, Mounif El-Yousseff, Albert J. Czaja

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Abstract

Background & Aims: Celiac disease (CD) is a chronic inflammatory disorder of the small intestine that is strongly associated with certain HLA molecules encoded by DQA and DQB genes. The aim of this study was to examine the role of DQA and DQB alleles in determining the risk for and the age of onset and severity of CD in an American population. Methods: High-resolution class 2 HLA genotyping was performed in a population-based sample (n = 84) of southeastern Minnesota residents with CD and a comparable control group (n = 102) to determine the contribution of DQA and DQB alleles to disease risk. Logistic regression modeling was used to examine the relative and absolute risks of CD. Results: Ninety-seven percent of CD patients carried both of the HLA alleles, DQA1*05 and DQB1*02. Those who carried a second allele of DQB1*02 were 5 times more likely to have CD than those with just one (95% confidence interval, 1.4-18.1). The carriage of 2 copies of DQB1*02 did not predict either an earlier age of onset or severity of disease. Conclusions: Both HLA alleles DQA1*05 and DQB1*02 are associated with a greatly increased risk of CD, although the latter has the greater effect. Carrying 2 copies of DQB1*02 was associated with an even greater risk for disease but did not predict an earlier age of onset and diagnosis or disease severity. Assessing the copy number of the DQB1*02 allele might allow for the stratification of disease risk.

Original languageEnglish (US)
Pages (from-to)1406-1412
Number of pages7
JournalClinical Gastroenterology and Hepatology
Volume5
Issue number12
DOIs
StatePublished - Dec 2007

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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    Murray, J. A., Moore, S. B., van Dyke, C. T., Lahr, B. D., Dierkhising, R. A., Zinsmeister, A. R., Melton, L. J., Kroning, C. M., El-Yousseff, M., & Czaja, A. J. (2007). HLA DQ Gene Dosage and Risk and Severity of Celiac Disease. Clinical Gastroenterology and Hepatology, 5(12), 1406-1412. https://doi.org/10.1016/j.cgh.2007.08.013