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Analysis of HLA and non-HLA alleles can identify individuals at high risk for celiac disease.
Gastroenterology. 2009 Sep; 137(3):834-40, 840.e1-3.G

Abstract

BACKGROUND & AIMS

Celiac disease (CD) is a common chronic disorder of the small intestine, resulting from aberrant cellular responses to gluten peptides, and often remains undiagnosed. It is a complex genetic disorder, although 95% of the patients carry the risk heterodimer human leukocyte antigen (HLA)-DQ2. Genome-wide association studies on CD have identified 9 non-HLA loci that also contribute to CD risk, most of which are shared with other immune-related diseases. Our aim is to predict the genetic risk for CD using HLA and non-HLA risk alleles.

METHODS

We selected 10 independent polymorphisms in 2,308 cases and 4,585 controls from Dutch, UK, and Irish populations and categorized the individuals into 3 risk groups, based on their HLA-DQ2 genotype. We used the summed number of non-HLA risk alleles per individual to analyze their cumulative effect on CD risk, adjusting for gender and population group in logistic regression analysis. We validated our findings in 436 Italian cases and 532 controls.

RESULTS

CD cases carried more non-HLA risk alleles than controls: individuals carrying > or = 13 risk alleles had a higher CD risk (odds ratio, 6.2; 95% confidence interval, 4.1-9.3) compared with those carrying 0-5 risk alleles. Combining HLA and non-HLA risk genotypes in one model increases sensitivity by 6.2% compared with using only HLA for identification of high-risk individuals with slight decrease in specificity.

CONCLUSIONS

We can use non-HLA risk factors for CD to improve identification of high-risk individuals. Our risk model is a first step toward better diagnosis and prognosis in high-risk families and population-based screening.

Authors+Show Affiliations

Department of Genetics, University Medical Centre of Groningen, University of Groningen, Groningen, The Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19454285

Citation

Romanos, Jihane, et al. "Analysis of HLA and non-HLA Alleles Can Identify Individuals at High Risk for Celiac Disease." Gastroenterology, vol. 137, no. 3, 2009, pp. 834-40, 840.e1-3.
Romanos J, van Diemen CC, Nolte IM, et al. Analysis of HLA and non-HLA alleles can identify individuals at high risk for celiac disease. Gastroenterology. 2009;137(3):834-40, 840.e1-3.
Romanos, J., van Diemen, C. C., Nolte, I. M., Trynka, G., Zhernakova, A., Fu, J., Bardella, M. T., Barisani, D., McManus, R., van Heel, D. A., & Wijmenga, C. (2009). Analysis of HLA and non-HLA alleles can identify individuals at high risk for celiac disease. Gastroenterology, 137(3), 834-40, e1-3. https://doi.org/10.1053/j.gastro.2009.05.040
Romanos J, et al. Analysis of HLA and non-HLA Alleles Can Identify Individuals at High Risk for Celiac Disease. Gastroenterology. 2009;137(3):834-40, 840.e1-3. PubMed PMID: 19454285.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Analysis of HLA and non-HLA alleles can identify individuals at high risk for celiac disease. AU - Romanos,Jihane, AU - van Diemen,Cleo C, AU - Nolte,Ilja M, AU - Trynka,Gosia, AU - Zhernakova,Alexandra, AU - Fu,Jingyuan, AU - Bardella,Maria Teresa, AU - Barisani,Donatella, AU - McManus,Ross, AU - van Heel,David A, AU - Wijmenga,Cisca, Y1 - 2009/05/18/ PY - 2009/02/17/received PY - 2009/05/07/revised PY - 2009/05/13/accepted PY - 2009/5/21/entrez PY - 2009/5/21/pubmed PY - 2009/9/16/medline SP - 834-40, 840.e1-3 JF - Gastroenterology JO - Gastroenterology VL - 137 IS - 3 N2 - BACKGROUND & AIMS: Celiac disease (CD) is a common chronic disorder of the small intestine, resulting from aberrant cellular responses to gluten peptides, and often remains undiagnosed. It is a complex genetic disorder, although 95% of the patients carry the risk heterodimer human leukocyte antigen (HLA)-DQ2. Genome-wide association studies on CD have identified 9 non-HLA loci that also contribute to CD risk, most of which are shared with other immune-related diseases. Our aim is to predict the genetic risk for CD using HLA and non-HLA risk alleles. METHODS: We selected 10 independent polymorphisms in 2,308 cases and 4,585 controls from Dutch, UK, and Irish populations and categorized the individuals into 3 risk groups, based on their HLA-DQ2 genotype. We used the summed number of non-HLA risk alleles per individual to analyze their cumulative effect on CD risk, adjusting for gender and population group in logistic regression analysis. We validated our findings in 436 Italian cases and 532 controls. RESULTS: CD cases carried more non-HLA risk alleles than controls: individuals carrying > or = 13 risk alleles had a higher CD risk (odds ratio, 6.2; 95% confidence interval, 4.1-9.3) compared with those carrying 0-5 risk alleles. Combining HLA and non-HLA risk genotypes in one model increases sensitivity by 6.2% compared with using only HLA for identification of high-risk individuals with slight decrease in specificity. CONCLUSIONS: We can use non-HLA risk factors for CD to improve identification of high-risk individuals. Our risk model is a first step toward better diagnosis and prognosis in high-risk families and population-based screening. SN - 1528-0012 UR - https://www.unboundmedicine.com/medline/citation/19454285/Analysis_of_HLA_and_non_HLA_alleles_can_identify_individuals_at_high_risk_for_celiac_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0016-5085(09)00772-0 DB - PRIME DP - Unbound Medicine ER -