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

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.

The prevalence of HPA‐1a alloimmunization and the potential risk of FNAIT depend on both the DRB3*01:01 allele and associated DR‐DQ haplotypes

“…In addition to this, other HLA alleles and haplotypes have also been associated with different diseases. One such well‐known association is the linkage between DQB1*02 and celiac disease, where the disease also is shown to be more frequent with a double dose of DQB1*02 45 …”

Response to Letter to the Editor: Relevance of HLA‐DQB1*02 allele in predisposing to coeliac disease

“…The role of risk stratification based on HLA gene dose has not been fully understood, and results of studies vary and, sometimes, oppose each other. Our recently published meta-analysis showed a significant association between HLA-DQB1*02 and the clinical phenotype of coeliac disease: classical clinical presentation proved to be more frequent in patients with a double dose of HLA-DQB1*02 (Bajor, Szakács, Farkas, et al, 2019).…”

“…Their serological results and the severity of villous atrophy were similar to those with single and double doses.The role of risk stratification based on HLA gene dose has not been fully understood, and results of studies vary and, sometimes, oppose each other. Our recently published meta-analysis showed a significant association between HLA-DQB1*02 and the clinical phenotype of coeliac disease: classical clinical presentation proved to be more frequent in patients with a double dose of HLA-DQB1*02 (Bajor, Szakács, Farkas, et al, 2019).We share the opinion of Dr. Poddighe on the importance of developing screening strategies in populations at risk (Poddighe, 2018). Indeed, the two-step HLA-based screening strategy can be cost-effective, but one must act with caution because this strategy does not identify patients with DQ8 comprising 5%-10% of coeliac population.…”

Vaccinations and Immune Response in Celiac Disease

“…CD develops in genetically predisposed subjects who, in response to multiple environmental factors, manifest an immune reaction that is triggered by the ingestion of gluten [ 2 ]. Genetic predisposition is closely related to the presence of human leukocyte antigen (HLA)-DQ2 or DQ8 [ 3 ]. Recently, the European Society of Paediatric Gastroenterology, Hepatology and Nutrition updated and expanded evidence-based guidelines for diagnosing CD.…”