Classical celiac disease is more frequent with a double dose of HLA-DQB102: A systematic review with meta-analysis

Judit Bajor, Zsolt Szakács, Nelli Farkas, P. Hegyi, Anita Illés, Margit Solymár, Erika Pétervári, M. Balaskó, G. Pár, Patrícia Sarlós, Ákos Szűcs, József Czimmer, Kata Szemes, Orsolya Huszár, Péter Varjú, A. Vincze

Research output: Contribution to journalReview article

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Abstract

Background and aims Experimental data suggest that the HLA-DQ2 gene dose has a strong quantitative effect on clinical outcomes and severity of celiac disease (CD). We aimed to conduct a meta-analysis with systematic review to investigate the association between HLA-DQB1*02 gene doses and the characteristics of CD. Methods We searched seven medical databases for studies discussing HLA-DQB1 gene dose in CD and various disease characteristics, such as clinical presentation, histology, age at diagnosis, and comorbidities. Odds ratios (OR, for categorical variables) and weighted mean differences (for age) were calculated to compare patients with a double dose of HLA-DQB1*02 versus those with single and zero doses. Heterogeneity was tested with I 2 -statistics and explored by study subgroups (children and adults). Results Twenty-four publications were eligible for meta-analysis. Classical CD was more frequent with a double versus single dose of the HLA-DQB1*02 allele (OR = 1.758, 95%CI: 1.148–2.692, I 2 = 0.0%). In pediatric studies, gene dose effect was more prominent (OR = 2.082, 95%CI: 1.189–3.646, I 2 = 0.0% and OR = 3.139, 95%CI: 1.142–8.630, I 2 = 0.0% for the comparisons of double versus single and double versus zero dose, respectively). Atrophic histology was more prevalent with a double versus zero dose (OR = 2.626, CI: 1.060–6.505, I 2 = 21.3%). We observed no gene dose effect regarding diarrhea, age at diagnosis, the severity of villous atrophy, and the association with type 1 diabetes mellitus. Conclusion A double dose of HLA-DQB1*02 gene seems to predispose patients to developing classical CD and villous atrophy. Risk stratification by HLA-DQB1*02 gene dose requires further clarification due to the limited available evidence.

Original languageEnglish
Article numbere0212329
JournalPloS one
Volume14
Issue number2
DOIs
Publication statusPublished - Feb 1 2019

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celiac disease
systematic review
Celiac Disease
meta-analysis
Meta-Analysis
Genes
dosage
Histology
Atrophy
genes
Pediatrics
atrophy
histology
Medical problems
Type 1 Diabetes Mellitus
Publications
HLA-DQB1 antigen
Comorbidity
Diarrhea
Alleles

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Classical celiac disease is more frequent with a double dose of HLA-DQB102 : A systematic review with meta-analysis. / Bajor, Judit; Szakács, Zsolt; Farkas, Nelli; Hegyi, P.; Illés, Anita; Solymár, Margit; Pétervári, Erika; Balaskó, M.; Pár, G.; Sarlós, Patrícia; Szűcs, Ákos; Czimmer, József; Szemes, Kata; Huszár, Orsolya; Varjú, Péter; Vincze, A.

In: PloS one, Vol. 14, No. 2, e0212329, 01.02.2019.

Research output: Contribution to journalReview article

Bajor, J, Szakács, Z, Farkas, N, Hegyi, P, Illés, A, Solymár, M, Pétervári, E, Balaskó, M, Pár, G, Sarlós, P, Szűcs, Á, Czimmer, J, Szemes, K, Huszár, O, Varjú, P & Vincze, A 2019, 'Classical celiac disease is more frequent with a double dose of HLA-DQB102: A systematic review with meta-analysis', PloS one, vol. 14, no. 2, e0212329. https://doi.org/10.1371/journal.pone.0212329
Bajor, Judit ; Szakács, Zsolt ; Farkas, Nelli ; Hegyi, P. ; Illés, Anita ; Solymár, Margit ; Pétervári, Erika ; Balaskó, M. ; Pár, G. ; Sarlós, Patrícia ; Szűcs, Ákos ; Czimmer, József ; Szemes, Kata ; Huszár, Orsolya ; Varjú, Péter ; Vincze, A. / Classical celiac disease is more frequent with a double dose of HLA-DQB102 : A systematic review with meta-analysis. In: PloS one. 2019 ; Vol. 14, No. 2.
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abstract = "Background and aims Experimental data suggest that the HLA-DQ2 gene dose has a strong quantitative effect on clinical outcomes and severity of celiac disease (CD). We aimed to conduct a meta-analysis with systematic review to investigate the association between HLA-DQB1*02 gene doses and the characteristics of CD. Methods We searched seven medical databases for studies discussing HLA-DQB1 gene dose in CD and various disease characteristics, such as clinical presentation, histology, age at diagnosis, and comorbidities. Odds ratios (OR, for categorical variables) and weighted mean differences (for age) were calculated to compare patients with a double dose of HLA-DQB1*02 versus those with single and zero doses. Heterogeneity was tested with I 2 -statistics and explored by study subgroups (children and adults). Results Twenty-four publications were eligible for meta-analysis. Classical CD was more frequent with a double versus single dose of the HLA-DQB1*02 allele (OR = 1.758, 95{\%}CI: 1.148–2.692, I 2 = 0.0{\%}). In pediatric studies, gene dose effect was more prominent (OR = 2.082, 95{\%}CI: 1.189–3.646, I 2 = 0.0{\%} and OR = 3.139, 95{\%}CI: 1.142–8.630, I 2 = 0.0{\%} for the comparisons of double versus single and double versus zero dose, respectively). Atrophic histology was more prevalent with a double versus zero dose (OR = 2.626, CI: 1.060–6.505, I 2 = 21.3{\%}). We observed no gene dose effect regarding diarrhea, age at diagnosis, the severity of villous atrophy, and the association with type 1 diabetes mellitus. Conclusion A double dose of HLA-DQB1*02 gene seems to predispose patients to developing classical CD and villous atrophy. Risk stratification by HLA-DQB1*02 gene dose requires further clarification due to the limited available evidence.",
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T1 - Classical celiac disease is more frequent with a double dose of HLA-DQB102

T2 - A systematic review with meta-analysis

AU - Bajor, Judit

AU - Szakács, Zsolt

AU - Farkas, Nelli

AU - Hegyi, P.

AU - Illés, Anita

AU - Solymár, Margit

AU - Pétervári, Erika

AU - Balaskó, M.

AU - Pár, G.

AU - Sarlós, Patrícia

AU - Szűcs, Ákos

AU - Czimmer, József

AU - Szemes, Kata

AU - Huszár, Orsolya

AU - Varjú, Péter

AU - Vincze, A.

PY - 2019/2/1

Y1 - 2019/2/1

N2 - Background and aims Experimental data suggest that the HLA-DQ2 gene dose has a strong quantitative effect on clinical outcomes and severity of celiac disease (CD). We aimed to conduct a meta-analysis with systematic review to investigate the association between HLA-DQB1*02 gene doses and the characteristics of CD. Methods We searched seven medical databases for studies discussing HLA-DQB1 gene dose in CD and various disease characteristics, such as clinical presentation, histology, age at diagnosis, and comorbidities. Odds ratios (OR, for categorical variables) and weighted mean differences (for age) were calculated to compare patients with a double dose of HLA-DQB1*02 versus those with single and zero doses. Heterogeneity was tested with I 2 -statistics and explored by study subgroups (children and adults). Results Twenty-four publications were eligible for meta-analysis. Classical CD was more frequent with a double versus single dose of the HLA-DQB1*02 allele (OR = 1.758, 95%CI: 1.148–2.692, I 2 = 0.0%). In pediatric studies, gene dose effect was more prominent (OR = 2.082, 95%CI: 1.189–3.646, I 2 = 0.0% and OR = 3.139, 95%CI: 1.142–8.630, I 2 = 0.0% for the comparisons of double versus single and double versus zero dose, respectively). Atrophic histology was more prevalent with a double versus zero dose (OR = 2.626, CI: 1.060–6.505, I 2 = 21.3%). We observed no gene dose effect regarding diarrhea, age at diagnosis, the severity of villous atrophy, and the association with type 1 diabetes mellitus. Conclusion A double dose of HLA-DQB1*02 gene seems to predispose patients to developing classical CD and villous atrophy. Risk stratification by HLA-DQB1*02 gene dose requires further clarification due to the limited available evidence.

AB - Background and aims Experimental data suggest that the HLA-DQ2 gene dose has a strong quantitative effect on clinical outcomes and severity of celiac disease (CD). We aimed to conduct a meta-analysis with systematic review to investigate the association between HLA-DQB1*02 gene doses and the characteristics of CD. Methods We searched seven medical databases for studies discussing HLA-DQB1 gene dose in CD and various disease characteristics, such as clinical presentation, histology, age at diagnosis, and comorbidities. Odds ratios (OR, for categorical variables) and weighted mean differences (for age) were calculated to compare patients with a double dose of HLA-DQB1*02 versus those with single and zero doses. Heterogeneity was tested with I 2 -statistics and explored by study subgroups (children and adults). Results Twenty-four publications were eligible for meta-analysis. Classical CD was more frequent with a double versus single dose of the HLA-DQB1*02 allele (OR = 1.758, 95%CI: 1.148–2.692, I 2 = 0.0%). In pediatric studies, gene dose effect was more prominent (OR = 2.082, 95%CI: 1.189–3.646, I 2 = 0.0% and OR = 3.139, 95%CI: 1.142–8.630, I 2 = 0.0% for the comparisons of double versus single and double versus zero dose, respectively). Atrophic histology was more prevalent with a double versus zero dose (OR = 2.626, CI: 1.060–6.505, I 2 = 21.3%). We observed no gene dose effect regarding diarrhea, age at diagnosis, the severity of villous atrophy, and the association with type 1 diabetes mellitus. Conclusion A double dose of HLA-DQB1*02 gene seems to predispose patients to developing classical CD and villous atrophy. Risk stratification by HLA-DQB1*02 gene dose requires further clarification due to the limited available evidence.

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