Abstract
Background and Objectives: Celiac disease (CD) is a multifactorial immune-mediated disorder, triggered by the ingestion of gluten in genetically-predisposed subjects carrying MHC-DQ2 and -DQ8 heterodimers, which are encoded by four HLA-DQ allelic variants, overall. This meta-analysis aims at providing further epidemiological support to the predominant relevance of one specific allele, namely HLA-DQB1*02, in the predisposition and genetic risk of CD. Materials and Methods: We performed a search of MEDLINE/PubMed, Embase, Web of Science, and Scopus, retrieving all publications (case–control study, cross-sectional, and retrospective cohort study) on the association between HLA class II polymorphisms and first-degree relatives (FDRs) of children with CD. After a critical reading of the articles, two investigators independently performed data extraction according to the following inclusion criteria: HLA class II genes, any DQ and DR molecules, and CD diagnosed following the current clinical guidelines. A third participant was consulted for discussion to reach an agreement concerning discrepancies. Results: Our search strategy selected 14 studies as being eligible for inclusion, and those were submitted for data extraction and analysis. These studies were published between 1999 and 2016 and, collectively, enrolled 3063 FDRs. Positive and negative likelihood ratios (LR+ and LR−, respectively) for CD diagnosis, according to the presence of the HLA-DQ genotype coding a complete MHC-DQ2 and/or MHC-DQ8 molecules, were 1.449 (CI 1.279–1.642) and 0.187 (CI 0.096–0.362), respectively. If only the isolated presence of HLA-DQB1*02 allele is considered, the pooled estimation of LR+ was 1.659 (CI 1.302–2.155) and, importantly, the LR− still showed a very good discriminatory power of 0.195 (CI 0.068–0.558). Conclusions: Through our differential meta-analysis, comparing the presence of the genotype coding the full MHC-DQ2 and/or DQ8 molecules with the isolated presence of HLA-DQB1*02 allelic variant, we found that the LR− of the latter analysis maintained the same value. This observation, along with previous evidences, might be useful to consider potential cost-effective widened screening strategies for CD in children.
Highlights
Celiac disease (CD) is a multifactorial immune-mediated disorder, triggered by the ingestion of gluten and other gluten-related proteins in genetically predisposed subjects
Protocol meta-analysis, we aimed at quantitatively evaluating the association between HLA-DQ polymorphisms and the susceptibility
We performed a search of PubMed, EMBASE, Web of Science, and Scopus, retrieving all publications on the association between HLA class II polymorphisms and first-degree relatives (FDRs) of CD children
Summary
Celiac disease (CD) is a multifactorial immune-mediated disorder, triggered by the ingestion of gluten and other gluten-related proteins in genetically predisposed subjects. The HLA-DQ alleles, coding α and β chains of the MHC-DQ2 and -DQ8 heterodimers, have been shown to be a necessary, but not sufficient, immunogenetic background for the development of CD These HLA-DQ haplotypes have been estimated to contribute up to 25%–40% of the genetic risk for CD and have been reported to be present in around 35–40% of the general population in North America and Europe, where the prevalence of CD is close to 1% and, probably, even more if only the pediatric population is considered [1,2]. Results: Our search strategy selected 14 studies as being eligible for inclusion, and those were submitted for data extraction and analysis These studies were published between 1999 and 2016 and, collectively, enrolled 3063 FDRs. Positive and negative likelihood ratios (LR+ and LR−, respectively) for CD diagnosis, according to the presence of the HLA-DQ genotype coding a complete MHC-DQ2 and/or MHC-DQ8 molecules, were 1.449 (CI 1.279–1.642) and 0.187
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