HLA-DQ genetics in children with celiac disease

A meta-analysis suggesting a two-step genetic screening procedure starting with HLA-DQ β chains

Annalisa De Silvestri, Cristina Capittini, Dimitri Poddighe, Chiara Valsecchi, Gianluigi Marseglia, Sara Carlotta Tagliacarne, Valeria Scotti, Chiara Rebuffi, Annamaria Pasi, Miryam Martinetti, Carmine Tinelli

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

BackgroundSpecific 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.MethodsAfter 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.ResultsIn 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.ConclusionThe 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.

Original languageEnglish
Pages (from-to)564-572
Number of pages9
JournalPediatric Research
Volume83
Issue number3
DOIs
Publication statusPublished - Mar 1 2018
Externally publishedYes

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HLA-DQ Antigens
Genetic Testing
Celiac Disease
Meta-Analysis
Odds Ratio
Case-Control Studies
Alleles
Genotype
MHC Class II Genes
Population
Publications
Cohort Studies
Pediatrics

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

HLA-DQ genetics in children with celiac disease : A meta-analysis suggesting a two-step genetic screening procedure starting with HLA-DQ β chains. / De Silvestri, Annalisa; Capittini, Cristina; Poddighe, Dimitri; Valsecchi, Chiara; Marseglia, Gianluigi; Tagliacarne, Sara Carlotta; Scotti, Valeria; Rebuffi, Chiara; Pasi, Annamaria; Martinetti, Miryam; Tinelli, Carmine.

In: Pediatric Research, Vol. 83, No. 3, 01.03.2018, p. 564-572.

Research output: Contribution to journalArticle

De Silvestri, A, Capittini, C, Poddighe, D, Valsecchi, C, Marseglia, G, Tagliacarne, SC, Scotti, V, Rebuffi, C, Pasi, A, Martinetti, M & Tinelli, C 2018, 'HLA-DQ genetics in children with celiac disease: A meta-analysis suggesting a two-step genetic screening procedure starting with HLA-DQ β chains', Pediatric Research, vol. 83, no. 3, pp. 564-572. https://doi.org/10.1038/pr.2017.307
De Silvestri, Annalisa ; Capittini, Cristina ; Poddighe, Dimitri ; Valsecchi, Chiara ; Marseglia, Gianluigi ; Tagliacarne, Sara Carlotta ; Scotti, Valeria ; Rebuffi, Chiara ; Pasi, Annamaria ; Martinetti, Miryam ; Tinelli, Carmine. / HLA-DQ genetics in children with celiac disease : A meta-analysis suggesting a two-step genetic screening procedure starting with HLA-DQ β chains. In: Pediatric Research. 2018 ; Vol. 83, No. 3. pp. 564-572.
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abstract = "BackgroundSpecific 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.MethodsAfter 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.ResultsIn 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.ConclusionThe 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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T2 - A meta-analysis suggesting a two-step genetic screening procedure starting with HLA-DQ β chains

AU - De Silvestri, Annalisa

AU - Capittini, Cristina

AU - Poddighe, Dimitri

AU - Valsecchi, Chiara

AU - Marseglia, Gianluigi

AU - Tagliacarne, Sara Carlotta

AU - Scotti, Valeria

AU - Rebuffi, Chiara

AU - Pasi, Annamaria

AU - Martinetti, Miryam

AU - Tinelli, Carmine

PY - 2018/3/1

Y1 - 2018/3/1

N2 - BackgroundSpecific 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.MethodsAfter 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.ResultsIn 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.ConclusionThe 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.

AB - BackgroundSpecific 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.MethodsAfter 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.ResultsIn 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.ConclusionThe 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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