Relevance of HLA-DQB1*02 Allele in the Genetic Predisposition of Children with Celiac Disease: Additional Cues from a Meta-Analysis
<i>Background and Objectives:</i> 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-analy...
Main Authors: | , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2019-05-01
|
Series: | Medicina |
Subjects: | |
Online Access: | https://www.mdpi.com/1010-660X/55/5/190 |
id |
doaj-f2768083831345f0ba3449a9305acbde |
---|---|
record_format |
Article |
spelling |
doaj-f2768083831345f0ba3449a9305acbde2020-11-24T21:54:37ZengMDPI AGMedicina1010-660X2019-05-0155519010.3390/medicina55050190medicina55050190Relevance of HLA-DQB1*02 Allele in the Genetic Predisposition of Children with Celiac Disease: Additional Cues from a Meta-AnalysisCristina Capittini0Annalisa De Silvestri1Chiara Rebuffi2Carmine Tinelli3Dimitri Poddighe4Scientific Direction, Clinical Epidemiology and Biometric Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, ItalyScientific Direction, Clinical Epidemiology and Biometric Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, ItalyGrant Office and Scientific Documentation Center, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, ItalyScientific Direction, Clinical Epidemiology and Biometric Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, ItalyDepartment of Medicine, Nazarbayev University School of Medicine, Nur-Sultan City 010000, Kazakhstan<i>Background and Objectives:</i> 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. <i>Materials and Methods:</i> 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. <i>Results:</i> 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). <i>Conclusions:</i> 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.https://www.mdpi.com/1010-660X/55/5/190celiac diseasechildrenHLA-DQB1*02screeningfirst-degree relatives |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Cristina Capittini Annalisa De Silvestri Chiara Rebuffi Carmine Tinelli Dimitri Poddighe |
spellingShingle |
Cristina Capittini Annalisa De Silvestri Chiara Rebuffi Carmine Tinelli Dimitri Poddighe Relevance of HLA-DQB1*02 Allele in the Genetic Predisposition of Children with Celiac Disease: Additional Cues from a Meta-Analysis Medicina celiac disease children HLA-DQB1*02 screening first-degree relatives |
author_facet |
Cristina Capittini Annalisa De Silvestri Chiara Rebuffi Carmine Tinelli Dimitri Poddighe |
author_sort |
Cristina Capittini |
title |
Relevance of HLA-DQB1*02 Allele in the Genetic Predisposition of Children with Celiac Disease: Additional Cues from a Meta-Analysis |
title_short |
Relevance of HLA-DQB1*02 Allele in the Genetic Predisposition of Children with Celiac Disease: Additional Cues from a Meta-Analysis |
title_full |
Relevance of HLA-DQB1*02 Allele in the Genetic Predisposition of Children with Celiac Disease: Additional Cues from a Meta-Analysis |
title_fullStr |
Relevance of HLA-DQB1*02 Allele in the Genetic Predisposition of Children with Celiac Disease: Additional Cues from a Meta-Analysis |
title_full_unstemmed |
Relevance of HLA-DQB1*02 Allele in the Genetic Predisposition of Children with Celiac Disease: Additional Cues from a Meta-Analysis |
title_sort |
relevance of hla-dqb1*02 allele in the genetic predisposition of children with celiac disease: additional cues from a meta-analysis |
publisher |
MDPI AG |
series |
Medicina |
issn |
1010-660X |
publishDate |
2019-05-01 |
description |
<i>Background and Objectives:</i> 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. <i>Materials and Methods:</i> 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. <i>Results:</i> 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). <i>Conclusions:</i> 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. |
topic |
celiac disease children HLA-DQB1*02 screening first-degree relatives |
url |
https://www.mdpi.com/1010-660X/55/5/190 |
work_keys_str_mv |
AT cristinacapittini relevanceofhladqb102alleleinthegeneticpredispositionofchildrenwithceliacdiseaseadditionalcuesfromametaanalysis AT annalisadesilvestri relevanceofhladqb102alleleinthegeneticpredispositionofchildrenwithceliacdiseaseadditionalcuesfromametaanalysis AT chiararebuffi relevanceofhladqb102alleleinthegeneticpredispositionofchildrenwithceliacdiseaseadditionalcuesfromametaanalysis AT carminetinelli relevanceofhladqb102alleleinthegeneticpredispositionofchildrenwithceliacdiseaseadditionalcuesfromametaanalysis AT dimitripoddighe relevanceofhladqb102alleleinthegeneticpredispositionofchildrenwithceliacdiseaseadditionalcuesfromametaanalysis |
_version_ |
1725866774473211904 |