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Stratifying risk for celiac disease in a large at-risk United States population by using HLA alleles.
Clin Gastroenterol Hepatol 2009; 7(9):966-71CG

Abstract

BACKGROUND & AIMS

Susceptibility to celiac disease (CD) is related to HLA-DQ2 and DQ8 alleles and the heterodimers they encode. The objective of this study was to stratify risk for CD on the basis of HLA-DQ genotype.

METHODS

DNA from 10,191 subjects who are at risk for CD was analyzed for HLA-DQ haplotypes. Individuals with CD were identified as those who tested positive for anti-endomysial immunoglobulin A (EMA+) in an immunofluorescence assay.

RESULTS

Samples homozygous for DQ2.5 (HLA-DQA1 05-DQB1 02) or DQ2.2/DQ2.5 (HLA-DQA1 05-DQB1 02 and HLA-DQA1 0201-DQB1 02) comprised 5.38% of the total; 28.28% of these were EMA+ (95% confidence interval [CI], 24.55-32.26). Of the samples that were DQ2.5 heterozygous (HLA-DQA1 05-DQB1 02); 9.09% were EMA+ (95% CI, 7.82-10.51). Among samples in which HLA-DQ8 (HLA-DQA1 03-DQB1 0302) was detected, 8.42% of homozygotes (95% CI, 3.71-15.92) and 2.11% of heterozygotes (95% CI, 1.43-3.00) were EMA+. Samples with DQ2.2/DQ8 or DQ2.5/DQ8 comprised 5.08% of the total, and 11.78% of these were EMA+ (95% CI, 9.13-14.87). HLA-DQ2 and HLA-DQ8 were absent in 4283 samples (42.03% of the total); 0.16% of these samples were EMA+ (95% CI, 0.07-0.34).

CONCLUSIONS

High-resolution, sequence-specific oligonucleotide probe typing with 35 DQA1-specific and 37 DQB1-specific probes of DNA from more than 10,000 subjects was used to stratify risk of CD in an at-risk U.S. population. DQ2 homozygosity (DQ2.5/DQ2.2+2.5) increased risk for CD, estimated by the rate of EMA positivity, compared with the entire sample population and other DQ genotypes. These data suggest a quantitative relationship between the type/proportion of DQ heterodimers and the risk of CD and identify potential immunotherapeutic targets.

Authors+Show Affiliations

Department of Pediatrics, Women's and Children's Hospital, University of Southern California Keck School of Medicine, Los Angeles, California 90033, USA. pietzak@usc.eduNo 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

19500688

Citation

Pietzak, Michelle M., et al. "Stratifying Risk for Celiac Disease in a Large At-risk United States Population By Using HLA Alleles." Clinical Gastroenterology and Hepatology : the Official Clinical Practice Journal of the American Gastroenterological Association, vol. 7, no. 9, 2009, pp. 966-71.
Pietzak MM, Schofield TC, McGinniss MJ, et al. Stratifying risk for celiac disease in a large at-risk United States population by using HLA alleles. Clin Gastroenterol Hepatol. 2009;7(9):966-71.
Pietzak, M. M., Schofield, T. C., McGinniss, M. J., & Nakamura, R. M. (2009). Stratifying risk for celiac disease in a large at-risk United States population by using HLA alleles. Clinical Gastroenterology and Hepatology : the Official Clinical Practice Journal of the American Gastroenterological Association, 7(9), pp. 966-71. doi:10.1016/j.cgh.2009.05.028.
Pietzak MM, et al. Stratifying Risk for Celiac Disease in a Large At-risk United States Population By Using HLA Alleles. Clin Gastroenterol Hepatol. 2009;7(9):966-71. PubMed PMID: 19500688.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Stratifying risk for celiac disease in a large at-risk United States population by using HLA alleles. AU - Pietzak,Michelle M, AU - Schofield,Timothy C, AU - McGinniss,Matthew J, AU - Nakamura,Robert M, Y1 - 2009/06/23/ PY - 2008/12/12/received PY - 2009/05/21/revised PY - 2009/05/23/accepted PY - 2009/6/9/entrez PY - 2009/6/9/pubmed PY - 2009/10/23/medline SP - 966 EP - 71 JF - Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association JO - Clin. Gastroenterol. Hepatol. VL - 7 IS - 9 N2 - BACKGROUND & AIMS: Susceptibility to celiac disease (CD) is related to HLA-DQ2 and DQ8 alleles and the heterodimers they encode. The objective of this study was to stratify risk for CD on the basis of HLA-DQ genotype. METHODS: DNA from 10,191 subjects who are at risk for CD was analyzed for HLA-DQ haplotypes. Individuals with CD were identified as those who tested positive for anti-endomysial immunoglobulin A (EMA+) in an immunofluorescence assay. RESULTS: Samples homozygous for DQ2.5 (HLA-DQA1 05-DQB1 02) or DQ2.2/DQ2.5 (HLA-DQA1 05-DQB1 02 and HLA-DQA1 0201-DQB1 02) comprised 5.38% of the total; 28.28% of these were EMA+ (95% confidence interval [CI], 24.55-32.26). Of the samples that were DQ2.5 heterozygous (HLA-DQA1 05-DQB1 02); 9.09% were EMA+ (95% CI, 7.82-10.51). Among samples in which HLA-DQ8 (HLA-DQA1 03-DQB1 0302) was detected, 8.42% of homozygotes (95% CI, 3.71-15.92) and 2.11% of heterozygotes (95% CI, 1.43-3.00) were EMA+. Samples with DQ2.2/DQ8 or DQ2.5/DQ8 comprised 5.08% of the total, and 11.78% of these were EMA+ (95% CI, 9.13-14.87). HLA-DQ2 and HLA-DQ8 were absent in 4283 samples (42.03% of the total); 0.16% of these samples were EMA+ (95% CI, 0.07-0.34). CONCLUSIONS: High-resolution, sequence-specific oligonucleotide probe typing with 35 DQA1-specific and 37 DQB1-specific probes of DNA from more than 10,000 subjects was used to stratify risk of CD in an at-risk U.S. population. DQ2 homozygosity (DQ2.5/DQ2.2+2.5) increased risk for CD, estimated by the rate of EMA positivity, compared with the entire sample population and other DQ genotypes. These data suggest a quantitative relationship between the type/proportion of DQ heterodimers and the risk of CD and identify potential immunotherapeutic targets. SN - 1542-7714 UR - https://www.unboundmedicine.com/medline/citation/19500688/Stratifying_risk_for_celiac_disease_in_a_large_at_risk_United_States_population_by_using_HLA_alleles_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1542-3565(09)00482-0 DB - PRIME DP - Unbound Medicine ER -