TY - JOUR
T1 - HLA-DQ genetics in children with celiac disease
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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U2 - 10.1038/pr.2017.307
DO - 10.1038/pr.2017.307
M3 - Article
AN - SCOPUS:85042701220
VL - 83
SP - 564
EP - 572
JO - Pediatric Research
JF - Pediatric Research
SN - 0031-3998
IS - 3
ER -