Abstract
Background and aimsExperimental 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.MethodsWe 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).ResultsTwenty-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.ConclusionA 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.
Highlights
Celiac disease (CD) is an immune-mediated systemic disorder triggered by gluten that occurs in genetically susceptible individuals [1, 2]
The HLA-DQ2 heterodimer consists of an α and a β subunit encoded by HLA-DQA1 05 and HLA-DQB1 02 alleles on chromosome 6, respectively [3]
Five studies [22, 23, 38, 43, 47] were included in the comparison of classical vs. non-classical CD regarding double vs. single dose of HLA-DQB1 02; of them, four [22, 23, 38, 43] were included in the analysis regarding double vs. zero dose of HLA-DQB1 02
Summary
Celiac disease (CD) is an immune-mediated systemic disorder triggered by gluten that occurs in genetically susceptible individuals [1, 2]. DQ2.2 molecules are structurally similar to DQ2.5, but the latter’s gluten peptide-binding properties are less prominent [3, 4, 6] Those with DQ2.2 haplotype are at high risk of CD but only if they are DQ2.2/2.5 or DQ2.2/DQ7 heterozygotes. In the latter case, functional DQ2.5 molecules can be assembled from α and β chains encoded separately on different chromosomes (DQA1 0505 and DQB1 0202, respectively); this constitution is called ‘DQ2 in trans’ [2, 5, 7, 8]. 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.
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