Retrospective Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Pediatr. Jul 9, 2022; 11(4): 351-359
Published online Jul 9, 2022. doi: 10.5409/wjcp.v11.i4.351
Frequency of celiac disease and distribution of HLA-DQ2/DQ8 haplotypes among siblings of children with celiac disease
Yasin Sahin, Serdar Mermer
Yasin Sahin, Department of Pediatric Gastroenterology, Mersin Training and Research Hospital, Mersin 33240, Mersin, Turkey
Serdar Mermer, Department of Medical Genetics, Mersin Training and Research Hospital, Mersin 33240, Mersin, Turkey
Author contributions: Sahin Y designed the study, analyzed the data, interpreted the data and wrote the manuscript; Mermer S designed the study and collected and analyzed the data; All authors had read and approved the final manuscript.
Institutional review board statement: The current study was approved by the Local Ethics Committee (Toros University, Mersin, Turkey, 17.06.2020/41).
Informed consent statement: Written informed consent was not obtained as the study is retrospective. However, the Local Ethics Committee approved the current study.
Conflict-of-interest statement: All the authors declare that they have no conflict of interest.
Data sharing statement: No additional data are available.
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Yasin Sahin, MD, Associate Professor, Department of Pediatric Gastroenterology, Mersin Training and Research Hospital, Korukent Mah. 96015 Sok. Mersin Entegre Sağlık Kampüsü 33240 Toroslar/Mersin, Mersin 33240, Mersin, Turkey. ysahin977@gmail.com
Received: January 10, 2022
Peer-review started: January 10, 2022
First decision: March 8, 2022
Revised: March 18, 2022
Accepted: June 3, 2022
Article in press: June 3, 2022
Published online: July 9, 2022
Processing time: 176 Days and 23.4 Hours
ARTICLE HIGHLIGHTS
Research background

Celiac disease (CD) is a systemic autoimmune disease triggered by gluten intake in genetically susceptible individuals. It is a multifactorial disease, but genetic factors play a major role in its etiology. It has been known that human leucocyte antigen (HLA)-DQ2/DQ8 genotypes are one of the most important predisposing genetic factors. The risk of developing CD in siblings of celiac patients is quite high because of having the same HLA genotypes and environmental triggers such as gut microbiome.

Research motivation

Although there are many studies on the frequency of CD in first-degree relatives of celiac patients, the number of studies investigating the frequency of CD and the distribution of HLA-DQ2/DQ8 in siblings of celiac patients is rare. Because of that, we aimed to evaluate the frequency of CD and the distribution of HLA-DQ2/DQ8 haplotypes in siblings of celiac patients.

Research objectives

To investigate the frequency of CD and the distribution of HLA-DQ2/DQ8 haplotypes in siblings of celiac patients.

Research methods

The current study was carried out between February 2017 and June 2020. Biopsy-proven celiac patients and their siblings were included in the study. CD was diagnosed according to the European Society for Paediatric Gastroenterology, Hepatology and Nutrition 2012 guidelines. In total, 57 celiac patients and their 112 siblings were included in the study. All siblings were on a gluten-containing diet. The HLA genotyping, tissue transglutaminase antibody IgA antibody test, and total IgA test were performed in all participants. Gastroduodenoscopy was performed in all patients with tissue transglutaminase antibody positivity. Four biopsies from the duodenum and at least one biopsy from the bulb were obtained. All intestinal biopsy specimens were evaluated according to the modified Marsh-Oberhuber classification.

Research results

HLA-DQ2/DQ8 alleles were detected in 98.2% of patients with CD and 90.2% of siblings of celiac patients. Tissue transglutaminase antibody IgA test was found to be positive in 16 siblings. CD was diagnosed in 12 siblings by intestinal biopsy. Seven of those twelve celiac patients had anemia, six of them had growth retardation, and four of them had no symptoms.

Research conclusions

The prevalence of CD was found to be 10.7% in siblings of celiac patients in our study, and this rate was 22.7 times higher than the general population. One-third of the siblings diagnosed with CD was asymptomatic. We detected HLA-DQ alleles in 98.2% of celiac patients and 100% in siblings diagnosed with CD. Thus, CD has been shown to be associated with HLA-DQ2 and HLA-DQ8 genotypes. In addition, 1 of the 2 siblings was diagnosed with CD 1 year later and the other 4 years later.

Research perspectives

According to the current study, we suggest that the siblings of celiac patients should be followed up with clinical findings as well as HLA analysis and serological examination. Since the risk of developing CD is much higher in asymptomatic siblings, we recommend that siblings should be screened for CD even if they are asymptomatic.