HLA DQ Gene Dosage and Risk and Severity of Celiac Disease

Overview

Journal Clin Gastroenterol Hepatol

Specialty Gastroenterology

Date 2007 Oct 9

PMID 17919990

Citations 33

Authors

Joseph A Murray

S Breanndan Moore

Carol T Van Dyke

Brian D Lahr

Ross A Dierkhising

Alan R Zinsmeister

L Joseph Melton 3rd

Cynthia M Kroning

Mounif El-Yousseff

Albert J Czaja

Affiliations

Soon will be listed here.

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.

Citing Articles

Association of HLA-DQ4/5 genotype polymorphisms with celiac disease in a group of children in Southwest Iran: A case-control study.

Keshtkari A, Danaei M, Mollaali M Health Sci Rep. 2024; 7(7):e2242.

PMID: 39011150 PMC: 11246975. DOI: 10.1002/hsr2.2242.

IgA nephropathy.

Stamellou E, Seikrit C, Tang S, Boor P, Tesar V, Floege J Nat Rev Dis Primers. 2023; 9(1):67.

PMID: 38036542 DOI: 10.1038/s41572-023-00476-9.

Cytological, molecular, cytogenetic, and physiological characterization of a novel immortalized human enteric glial cell line.

Zanoletti L, Valdata A, Nehlsen K, Faris P, Casali C, Cacciatore R Front Cell Neurosci. 2023; 17:1170309.

PMID: 37153631 PMC: 10158601. DOI: 10.3389/fncel.2023.1170309.

The Evolving Landscape of Biomarkers in Celiac Disease: Leading the Way to Clinical Development.

Smithson G, Siegelman J, Oki T, Maxwell J, Leffler D Front Immunol. 2021; 12:665756.

PMID: 33897715 PMC: 8060282. DOI: 10.3389/fimmu.2021.665756.

Refractory Celiac Disease Type II: A Case Report and Literature Review.

Chibbar R, Nostedt J, Mihalicz D, Deschenes J, McLean R, Dieleman L Front Med (Lausanne). 2020; 7:564875.

PMID: 33344468 PMC: 7746862. DOI: 10.3389/fmed.2020.564875.

References

Hoffenberg E, MacKenzie T, Barriga K, Eisenbarth G, Bao F, Haas J . A prospective study of the incidence of childhood celiac disease. J Pediatr. 2003; 143(3):308-14. DOI: 10.1067/s0022-3476(03)00282-8. View

Fasano A, Berti I, Gerarduzzi T, Not T, Colletti R, Drago S . Prevalence of celiac disease in at-risk and not-at-risk groups in the United States: a large multicenter study. Arch Intern Med. 2003; 163(3):286-92. DOI: 10.1001/archinte.163.3.286. View

Zubillaga P, Vidales M, Zubillaga I, Ormaechea V, Garcia-Urkia N, Vitoria J . HLA-DQA1 and HLA-DQB1 genetic markers and clinical presentation in celiac disease. J Pediatr Gastroenterol Nutr. 2002; 34(5):548-54. DOI: 10.1097/00005176-200205000-00014. View

Melton 3rd L . History of the Rochester Epidemiology Project. Mayo Clin Proc. 1996; 71(3):266-74. DOI: 10.4065/71.3.266. View

Lewis C, Book L, Black J, Sawitzke A, Cannon-Albright L, Zone J . Celiac disease and human leukocyte antigen genotype: accuracy of diagnosis in self-diagnosed individuals, dosage effect, and sibling risk. J Pediatr Gastroenterol Nutr. 2000; 31(1):22-7. DOI: 10.1097/00005176-200007000-00007. View

King A, Ciclitira P . Celiac disease: strongly heritable, oligogenic, but genetically complex. Mol Genet Metab. 2000; 71(1-2):70-5. DOI: 10.1006/mgme.2000.3067. View

Hoffenberg E, Emery L, Barriga K, Bao F, Taylor J, Eisenbarth G . Clinical features of children with screening-identified evidence of celiac disease. Pediatrics. 2004; 113(5):1254-9. DOI: 10.1542/peds.113.5.1254. View

Sollid L, McAdam S, Molberg O, Quarsten H, Louka A, Lundin K . Genes and environment in celiac disease. Acta Odontol Scand. 2001; 59(3):183-6. DOI: 10.1080/000163501750266792. View

Johnson T, Diamond B, Memeo L, Negulescu H, Hovhanissyan Z, Verkarre V . Relationship of HLA-DQ8 and severity of celiac disease: comparison of New York and Parisian cohorts. Clin Gastroenterol Hepatol. 2004; 2(10):888-94. DOI: 10.1016/s1542-3565(04)00390-8. View

10.

Murray J, Van Dyke C, Plevak M, Dierkhising R, Zinsmeister A, Melton 3rd L . Trends in the identification and clinical features of celiac disease in a North American community, 1950-2001. Clin Gastroenterol Hepatol. 2004; 1(1):19-27. DOI: 10.1053/jcgh.2003.50004. View

11.

Sollid L, Thorsby E . The primary association of celiac disease to a given HLA-DQ alpha/beta heterodimer explains the divergent HLA-DR associations observed in various Caucasian populations. Tissue Antigens. 1990; 36(3):136-7. DOI: 10.1111/j.1399-0039.1990.tb01816.x. View

12.

. Revised criteria for diagnosis of coeliac disease. Report of Working Group of European Society of Paediatric Gastroenterology and Nutrition. Arch Dis Child. 1990; 65(8):909-11. PMC: 1792502. DOI: 10.1136/adc.65.8.909. View

13.

Margaritte-Jeannin P, Babron M, Bourgey M, Louka A, Clot F, Percopo S . HLA-DQ relative risks for coeliac disease in European populations: a study of the European Genetics Cluster on Coeliac Disease. Tissue Antigens. 2004; 63(6):562-7. DOI: 10.1111/j.0001-2815.2004.00237.x. View

14.

Farrell R, Kelly C . Celiac sprue. N Engl J Med. 2002; 346(3):180-8. DOI: 10.1056/NEJMra010852. View

15.

Koning F, Schuppan D, Cerf-Bensussan N, Sollid L . Pathomechanisms in celiac disease. Best Pract Res Clin Gastroenterol. 2005; 19(3):373-87. DOI: 10.1016/j.bpg.2005.02.003. View

16.

Pena-Quintana L, Torres-Galvan M, Deniz-Naranjo M, Ortigosa-Castillo L, Ramos-Varela J, Calvo-Hernandez F . Assessment of the DQ heterodimer test in the diagnosis of celiac disease in the Canary Islands (Spain). J Pediatr Gastroenterol Nutr. 2003; 37(5):604-8. DOI: 10.1097/00005176-200311000-00019. View

17.

Kaukinen K, Partanen J, Maki M, Collin P . HLA-DQ typing in the diagnosis of celiac disease. Am J Gastroenterol. 2002; 97(3):695-9. DOI: 10.1111/j.1572-0241.2002.05471.x. View

18.

Mearin M, Biemond I, Pena A, Polanco I, Vazquez C, Schreuder G . HLA-DR phenotypes in Spanish coeliac children: their contribution to the understanding of the genetics of the disease. Gut. 1983; 24(6):532-7. PMC: 1420005. DOI: 10.1136/gut.24.6.532. View

19.

Ploski R, Ascher H, Sollid L . HLA genotypes and the increased incidence of coeliac disease in Sweden. Scand J Gastroenterol. 1996; 31(11):1092-7. DOI: 10.3109/00365529609036892. View

20.

Poland G, Ovsyannikova I, Jacobson R, Vierkant R, Jacobsen S, Pankratz V . Identification of an association between HLA class II alleles and low antibody levels after measles immunization. Vaccine. 2001; 20(3-4):430-8. DOI: 10.1016/s0264-410x(01)00346-2. View