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Effective detection of human leukocyte antigen risk alleles in celiac disease using tag single nucleotide polymorphisms.
PLoS One. 2008 May 28; 3(5):e2270.Plos

Abstract

BACKGROUND

The HLA genes, located in the MHC region on chromosome 6p21.3, play an important role in many autoimmune disorders, such as celiac disease (CD), type 1 diabetes (T1D), rheumatoid arthritis, multiple sclerosis, psoriasis and others. Known HLA variants that confer risk to CD, for example, include DQA1*05/DQB1*02 (DQ2.5) and DQA1*03/DQB1*0302 (DQ8). To diagnose the majority of CD patients and to study disease susceptibility and progression, typing these strongly associated HLA risk factors is of utmost importance. However, current genotyping methods for HLA risk factors involve many reactions, and are complicated and expensive. We sought a simple experimental approach using tagging SNPs that predict the CD-associated HLA risk factors.

METHODOLOGY

Our tagging approach exploits linkage disequilibrium between single nucleotide polymorphism (SNPs) and the CD-associated HLA risk factors DQ2.5 and DQ8 that indicate direct risk, and DQA1*0201/DQB1*0202 (DQ2.2) and DQA1*0505/DQB1*0301 (DQ7) that attribute to the risk of DQ2.5 to CD. To evaluate the predictive power of this approach, we performed an empirical comparison of the predicted DQ types, based on these six tag SNPs, with those executed with current validated laboratory typing methods of the HLA-DQA1 and -DQB1 genes in three large cohorts. The results were validated in three European celiac populations.

CONCLUSION

Using this method, only six SNPs were needed to predict the risk types carried by >95% of CD patients. We determined that for this tagging approach the sensitivity was >0.991, specificity >0.996 and the predictive value >0.948. Our results show that this tag SNP method is very accurate and provides an excellent basis for population screening for CD. This method is broadly applicable in European populations.

Authors+Show Affiliations

Department of Medical Genetics, University Medical Centre Utrecht, Utrecht, 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
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18509540

Citation

Monsuur, Alienke J., et al. "Effective Detection of Human Leukocyte Antigen Risk Alleles in Celiac Disease Using Tag Single Nucleotide Polymorphisms." PloS One, vol. 3, no. 5, 2008, pp. e2270.
Monsuur AJ, de Bakker PI, Zhernakova A, et al. Effective detection of human leukocyte antigen risk alleles in celiac disease using tag single nucleotide polymorphisms. PLoS ONE. 2008;3(5):e2270.
Monsuur, A. J., de Bakker, P. I., Zhernakova, A., Pinto, D., Verduijn, W., Romanos, J., Auricchio, R., Lopez, A., van Heel, D. A., Crusius, J. B., & Wijmenga, C. (2008). Effective detection of human leukocyte antigen risk alleles in celiac disease using tag single nucleotide polymorphisms. PloS One, 3(5), e2270. https://doi.org/10.1371/journal.pone.0002270
Monsuur AJ, et al. Effective Detection of Human Leukocyte Antigen Risk Alleles in Celiac Disease Using Tag Single Nucleotide Polymorphisms. PLoS ONE. 2008 May 28;3(5):e2270. PubMed PMID: 18509540.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effective detection of human leukocyte antigen risk alleles in celiac disease using tag single nucleotide polymorphisms. AU - Monsuur,Alienke J, AU - de Bakker,Paul I W, AU - Zhernakova,Alexandra, AU - Pinto,Dalila, AU - Verduijn,Willem, AU - Romanos,Jihane, AU - Auricchio,Renata, AU - Lopez,Ana, AU - van Heel,David A, AU - Crusius,J Bart A, AU - Wijmenga,Cisca, Y1 - 2008/05/28/ PY - 2008/01/30/received PY - 2008/04/03/accepted PY - 2008/5/30/pubmed PY - 2008/9/3/medline PY - 2008/5/30/entrez SP - e2270 EP - e2270 JF - PloS one JO - PLoS ONE VL - 3 IS - 5 N2 - BACKGROUND: The HLA genes, located in the MHC region on chromosome 6p21.3, play an important role in many autoimmune disorders, such as celiac disease (CD), type 1 diabetes (T1D), rheumatoid arthritis, multiple sclerosis, psoriasis and others. Known HLA variants that confer risk to CD, for example, include DQA1*05/DQB1*02 (DQ2.5) and DQA1*03/DQB1*0302 (DQ8). To diagnose the majority of CD patients and to study disease susceptibility and progression, typing these strongly associated HLA risk factors is of utmost importance. However, current genotyping methods for HLA risk factors involve many reactions, and are complicated and expensive. We sought a simple experimental approach using tagging SNPs that predict the CD-associated HLA risk factors. METHODOLOGY: Our tagging approach exploits linkage disequilibrium between single nucleotide polymorphism (SNPs) and the CD-associated HLA risk factors DQ2.5 and DQ8 that indicate direct risk, and DQA1*0201/DQB1*0202 (DQ2.2) and DQA1*0505/DQB1*0301 (DQ7) that attribute to the risk of DQ2.5 to CD. To evaluate the predictive power of this approach, we performed an empirical comparison of the predicted DQ types, based on these six tag SNPs, with those executed with current validated laboratory typing methods of the HLA-DQA1 and -DQB1 genes in three large cohorts. The results were validated in three European celiac populations. CONCLUSION: Using this method, only six SNPs were needed to predict the risk types carried by >95% of CD patients. We determined that for this tagging approach the sensitivity was >0.991, specificity >0.996 and the predictive value >0.948. Our results show that this tag SNP method is very accurate and provides an excellent basis for population screening for CD. This method is broadly applicable in European populations. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/18509540/Effective_detection_of_human_leukocyte_antigen_risk_alleles_in_celiac_disease_using_tag_single_nucleotide_polymorphisms_ L2 - http://dx.plos.org/10.1371/journal.pone.0002270 DB - PRIME DP - Unbound Medicine ER -