Prevalence of Celiac Disease Predisposing Genotypes, Including HLA-DQ2.2 Variant, in Brazilian Children

Abstract

-Background -Celiac disease is an autoimmune enteropathy triggered by the ingestion of gluten in genetically susceptible individuals. Almost all celiac patients carry immune recognition genes coding for HLA-DQ2.5 and DQ8 heterodimers. Over the last few years, great importance has been given to HLA-DQ2.2 as probable predisposing variant, although controversies still exist regarding its relevance. Objective -The aim of our study was to determine the possible existence of an association between HLA-DQ2.2 and celiac disease in Brazilian children by analyzing the prevalence of the predisposing variants for celiac disease in a representative group of children of a population in which this determination is still missing. Methods -HLA-DQ typing was performed in samples from a group of celiac (n=100) and non-celiac children (n=110). All samples were tested for the presence of the following variants: DQA1*05-DQB1*02 (DQ2.5), DQA1*03-DQB1*03:02 (DQ8) and DQA1*02:01-DQB1*02:02 (DQ2.2). Fisher`s exact test was used for statistical analysis. Results -In the group of 100 celiac children, 78 (78%) were positive for DQ2, 13 (13 %) were DQ2/DQ8 and 6 (6%) were DQ8 positives. The HLA-DQ pattern in the 110 non-celiac children was as follows: positive for DQ2 in 33 (29.9%) samples, in 2 (1.8 %) was positive for DQ2/DQ8 and in 15 (13.6%) was positive for DQ8. We found significant differences between the distribution of some but not all of the analyzed alleles when comparing celiac and non-celiac children. Conclusion -The genotyping of celiac disease HLA-DQ predisposing alleles showed similarities with HLA-DQ patterns found in both European and non-European populations, which may be a reflection of the miscegenation, which gave origin to the current Brazilian population. No significant association was found between DQ2.2 variant and celiac disease in the studied population.

Distribution of HLA‐DQ risk genotypes for celiac disease in Ethiopian children

“…34 Compared with our study, higher frequencies in the review by Alarida were reported from Mexico (28.3%), Turkey (22%), North India (15.6%) and Iran (12%). 34 Our findings indicate that more than half (51.6%) of the Ethiopian population is carrying any of the DQ2.5, DQ2.2 and DQ8 haplotypes, which was comparable with the Swedish references (55.9%) and other previous studies performed on the general population in Australia (55.9%), 37 Iran (58%), 18 Saudi Arabia (52.7%), 25 but slightly higher than Brazil (43.7%) 38,39 and Denmark (47.7%). 40 Although this study is the largest HLAgenotyped Ethiopian population to date, it is limited by the fact that children included in the present study were enrolled from only one region and therefore may not represent the whole population in Ethiopia.…”

HLA Haplotype Association with Celiac Disease in Albanian Pediatric Patients from Kosovo

“…In our cohort, 5.0% (3/60) of CD patients were HLA-DQ2- and/or HLA-DQ8-negative, which is comparable to the data originating from different countries reporting the percentage of HLA-DQ2/DQ8-negative CD patients between 0 and 10.0% [27, 29, 30, 32]. Two out of three HLA-DQ2/DQ8-negative CD patients were positive for the DQA1 part of the DQ2 heterodimer, carrying the HLA-DRB1 ∗ 11~DQA1 ∗ 05:05~DQB1 ∗ 03:01 haplotype.…”

Frequency of HLA‐DQ, susceptibility genotypes for celiac disease, in Brazilian newborns

“…According to recent studies the most prevalent haplotype found in patients lacking HLA-DQ2.5 and HLA-DQ8 is HLA-DQ2.2 (Mubarak et al, 2013). However, previous studies performed in a smaller Brazilian population sample suggest that HLA-DQ2.2 can only be considered a risk factor when associated with DQ2.5 (Almeida et al, 2016;Selleski et al, 2018).These variants are responsible for only 40% of the genetic risk of CD and are carried by approximately 30% of the general Caucasian population (Megiorni & Pizzuti, 2012), thus suggesting that HLA is only one of the regions that could confer risk of developing this condition. However, the other 60% of the genetic susceptibility to CD is shared by HLA class I and non-HLA genes, each of which is estimated to contribute only with a small risk effect (Trynka et al, 2011;Withoff, Li, Jonkers, & Wijmenga, 2016).…”