Abstract
Background
Specific HLA-DQ genes have been recognized as necessary - but not sufficient - factors for the occurrence of Celiac Disease (CD). Through a meta-analysis, evaluating the distribution of CD-related HLA genotypes in children, we aimed at providing insights for a potential widened screening strategy.
Methods
After a systematic search on the association between class II HLA genes and CD in children, 46 publications were obtained and assessed for eligibility. A total of 13 eligible studies were submitted to data extraction and analysis (10 case–control studies and 3 cohort studies). Case–control studies collectively enrolled 740 CD patients and 943 controls.
Results
In the population-stratified analysis, the following alleles conferred a significantly increased risk for CD: HLA-DQB1*02 (odds ratio [OR]=10.28) and HLA-DQB1*03:02 (OR=2.24). By drafting a risk gradient to develop CD according to HLA genetic background, the highest risk is confirmed to exist for DQ2/DQ2 homozygous subjects, regardless of the ethnicities (OR=5.4). Actually, the genotype DQ2/β2 showed basically the same risk (OR=5.3). Indeed, no differences have been found in CD risk between DQ2/β2 and DQ2/DQ2, as well as between DQ8/β2 and DQ2/DQ8, and between β2/DQX and DQ2/X.
Conclusion
The HLA-DQB1*02:01 allele is present in more than 90% CD children. In the perspective of a widened pediatric population screening for CD, a double-step process might be suggested: HLA-DQB1*02:01 might be investigated first and, only if this result is positive, children might be candidate for a prospective serologic screening, as a second step.
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This study was supported by the Fondazione IRCCS Policlinico San Matteo (Pavia, Italy), through research funds of the project no. 870-rcr2016-50.
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De Silvestri, A., Capittini, C., Poddighe, D. et al. HLA-DQ genetics in children with celiac disease: a meta-analysis suggesting a two-step genetic screening procedure starting with HLA-DQ β chains. Pediatr Res 83, 564–572 (2018). https://doi.org/10.1038/pr.2017.307
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DOI: https://doi.org/10.1038/pr.2017.307
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