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Meta-Analysis
. 2019 Feb 14;14(2):e0212329.
doi: 10.1371/journal.pone.0212329. eCollection 2019.

Classical celiac disease is more frequent with a double dose of HLA-DQB1*02: A systematic review with meta-analysis

Judit Bajor  1   2 , Zsolt Szakács  2   3 , Nelli Farkas  3   4 , Péter Hegyi  1   2   3   5 , Anita Illés  1 , Margit Solymár  3 , Erika Pétervári  3 , Márta Balaskó  3 , Gabriella Pár  1 , Patrícia Sarlós  1 , Ákos Szűcs  6 , József Czimmer  1 , Kata Szemes  1 , Orsolya Huszár  5 , Péter Varjú  3 , Áron Vincze  1   2
Affiliations
Meta-Analysis

Classical celiac disease is more frequent with a double dose of HLA-DQB1*02: A systematic review with meta-analysis

Judit Bajor et al. PLoS One. .

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 I2-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, I2 = 0.0%). In pediatric studies, gene dose effect was more prominent (OR = 2.082, 95%CI: 1.189-3.646, I2 = 0.0% and OR = 3.139, 95%CI: 1.142-8.630, I2 = 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, I2 = 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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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Flow chart of meta-analysis.
Fig 2
Fig 2. Odds ratios of classical presentation of CD at diagnosis with double dose vs. single dose of HLA-DQB1*02.
Patients with a double dose of HLA-DQB1*02 had classical CD more frequently compared to those having a single dose. This association was more prominent in children. Heterogeneity of the groups overall: I2 = 0.0%, p = 0.744; heterogeneity of the subgroup of children: I2 = 0.0%, p = 0.609. CI: confidence interval.
Fig 3
Fig 3. Odds ratios of classical presentation of CD at diagnosis with double dose vs. zero dose of HLA-DQB1*02.
A significant gene dose effect was detected in the subgroup of children. Heterogeneity of the groups overall: I2 = 40.7%, p = 0.168; heterogeneity of the subgroup of children: I2 = 0.0%, p = 0.747. CI: confidence interval.
Fig 4
Fig 4. Odds ratios of atrophic histology at diagnosis with double dose vs. single dose of HLA-DQB1*02.
We failed to detect a significant gene dose effect regarding diagnostic histology. Heterogeneity of the groups overall: I2 = 11.8%, p = 0.338; heterogeneity of the subgroup of adults: I2 = 0.0%, p = 0.682; heterogeneity of the subgroup of children: I2 = 71.6%, p = 0.061. CI: confidence interval.
Fig 5
Fig 5. Odds ratios of atrophic histology at diagnosis with double dose vs. zero dose of HLA-DQB1*02.
Patients with a double dose of the allele were more likely to have villous atrophy at diagnosis than those with a single dose of the allele. Heterogeneity of the groups overall: I2 = 21.3%, p = 0.260; heterogeneity of the subgroup of adults: I2 = 0.0%, p = 0.945; heterogeneity of the subgroup of children: I2 = 0.0%, p = 0.542. CI: confidence interval.
Fig 6
Fig 6. Summary of risk of bias in individual studies included in meta-analysis.
Green, red, and blue icons represent low, high, and uncertain risk of bias. Definitions of items are provided in S1 Table.
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