Relevance of HLA-DQB1*02 allele in the genetic predisposition of children with celiac disease: Additional cues from a meta-analysis

TY - JOUR

T1 - Relevance of HLA-DQB1*02 allele in the genetic predisposition of children with celiac disease

T2 - Additional cues from a meta-analysis

AU - Capittini, Cristina

AU - De Silvestri, Annalisa

AU - Rebuffi, Chiara

AU - Tinelli, Carmine

AU - Poddighe, Dimitri

PY - 2019/5/1

Y1 - 2019/5/1

N2 - 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.

AB - 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.

KW - Celiac disease

KW - Children

KW - First-degree relatives

KW - HLA-DQB102

KW - Screening

UR - http://www.scopus.com/inward/record.url?scp=85066848913&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85066848913&partnerID=8YFLogxK

U2 - 10.3390/medicina55050190

DO - 10.3390/medicina55050190

M3 - Review article

C2 - 31121940

AN - SCOPUS:85066848913

VL - 55

JO - Medicina

JF - Medicina

SN - 1010-660X

IS - 5

M1 - 190

ER -