Systematic Review
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 28, 2020; 26(12): 1365-1381
Published online Mar 28, 2020. doi: 10.3748/wjg.v26.i12.1365
Carrier frequency of HLA-DQB1*02 allele in patients affected with celiac disease: A systematic review assessing the potential rationale of a targeted allelic genotyping as a first-line screening
Dimitri Poddighe, Chiara Rebuffi, Annalisa De Silvestri, Cristina Capittini
Dimitri Poddighe, Department of Medicine, School of Medicine, Nazarbayev University, Nur-Sultan 010000, Kazakhstan
Chiara Rebuffi, Grant Office and Scientific Documentation Center, Fondazione IRCCS Policlinico San Matteo, Pavia 27100, Italy
Annalisa De Silvestri, Cristina Capittini, Scientific Direction, Clinical Epidemiology and Biometric Unit, Fondazione IRCCS Policlinico San Matteo, Pavia 27100, Italy
Cristina Capittini, Department of Biology and Biotechnology "Lazzaro Spallanzani", University of Pavia, Pavia 27100, Italy
Author contributions: Poddighe D conceived this manuscript; Poddighe D and Capittini C wrote this manuscript; Rebuffi C, Poddighe D, Capittini C and De Silvestri A all contributed and performed the systematic search and literature analysis.
Supported by the Nazarbayev University Faculty Development Competitive Research Grant 2020-2022, No. 240919FD3912.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
PRISMA 2009 Checklist statement: The authors prepared the manuscript according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Dimitri Poddighe, MD, MSc, Medical Specialist in Pediatrics; Assistant Professor, Department of Medicine, School of Medicine, Nazarbayev University, Kerei-Zhanibek Street 5/1, Nur-Sultan 010000, Kazakhstan. dimitri.poddighe@nu.edu.kz
Received: December 19, 2019
Peer-review started: December 19, 2019
First decision: January 12, 2020
Revised: March 10, 2020
Accepted: March 22, 2020
Article in press: March 22, 2020
Published online: March 28, 2020
Processing time: 99 Days and 19 Hours
ARTICLE HIGHLIGHTS
Research background

Celiac Disease (CD) is an immune-mediated disorder in which the HLA immunogenetic background (DQ2 and DQ8 heterodimers) is well known. This genetic factor is necessary – but not sufficient – to develop CD. Basically, almost 100% of CD patients are carriers of the aforementioned HLA-DQ background and several studies emphasized the main role of the HLA-DQB1*02 allele in such a genetic predisposition.

Research motivation

CD is underdiagnosed in both developing and developed countries, due to several aspects: Indeed, many patients present mild and/or atypical symptoms, without the presence of any recognized risk factors. Therefore, the possibility and feasibility of widened screening strategies to identify CD patients is still debated and this study might provide some additional insights, in order to find novel screening strategies.

Research objectives

Our aim was to define and assess the carrier frequency of the specific allelic variant HLA-DQB1*02 (coding the β chain of DQ2 heterodimer) in the population of patients diagnosed with CD.

Research methods

In order to achieve our aim, we performed a systematic review, according to the PRISMA guidelines, by retrieving all original articles (case series, case–control, cross-sectional, and retrospective cohort studies) describing CD patients’ HLA-DQB1 genotype in detail. Any original articles, in which CD patients’ HLA-DQB1 genotype was described in such a way and detail that the number of HLA-DQB1*02 carriers could be clearly defined (within the total of the respective CD population), were considered.

Research results

As a result of our literature search, 38 studies were finally included in the present systematic review, since those provided details of the HLA-DQB1 genotype in such a way that could allow to assess the HLA-DQB1*02 carrier frequency among CD patients. Among 4945 HLA-DQ genotyped CD patients, the HLA-DQB1*02 carrier frequency resulted to be 94.94%, meaning that only 5.06% of CD population was completely lacking this allelic variant. If only the CD pediatric population is considered, similar figures are obtained: Only 5.31% is lacking a copy of this allelic variant. Finally, if we consider only the studies whereby the prevalence of CD patients also affected with type 1 diabetes mellitus (DM1) was supposed or clearly established to be very low, the frequency of non-HLA-DQB1*02 carriers among CD patients dropped up to 3.65%.

Research conclusions

According to the findings of this systematic review, < 4%-5% of CD-predisposed children may be lost through a preliminary evaluation of the presence/absence of HLA-DQB1*02 allele, regardless of the presence of other HLA-DQB1 and HLA-DQA1 CD-predisposing alleles.

Research perspectives

A cost-effective and widened screening approach may be very helpful in both developed and developing countries, if a sustainable strategy could be implemented through a low-cost targeted genetic test for the HLA-DQB1*02 allelic presence, along with appropriate algorithms for serological screening in individuals resulting to be genetically predisposed to CD.