Association of HLA‐DQ4/5 genotype polymorphisms with celiac disease in a group of children in Southwest Iran: A case‐control study

TL;DR

This study explores the link between specific HLA-DQ4/5 genotypes and celiac disease in children from Southwest Iran, finding a strong association.

Contribution

The study identifies a novel association between HLA-DQ4/5 genotypes and celiac disease in a specific Iranian population.

Findings

The DQ4a*4b allele was most frequent in celiac disease samples (78%) with significant statistical association.

HLA-DQ4/DQ5 genotypes showed higher prevalence in celiac patients compared to controls (odds ratio = 6.5).

Significant associations were found between HLA-DQ4/5 genotypes and age (>9.5) and female gender.

Abstract

Celiac disease (CD) has proinflammatory and pathogenic immune responses to gluten in intestinal tissue, leading to structural changes in the mucosa of the small intestine. The association of human leukocyte antigen (HLA)‐DQ2 and DQ8 genotypes with CD has been previously reported. This test has a negative predictive value close to 100%, so its main purpose is to rule out the detection of CD completely or almost completely. There is limited information regarding HLA‐DQ4/5 in CD. This study was conducted to determine the HLA‐DQ4/5 genotypes in a group of Southwestern Iranian children with CD.

We conducted a case‐control study in Southwest Iran involving 100 participants, employing a nonprobabilistic sampling method. Samples were taken from participants' oral buccal mucosa at Imam Sajjad Hospital of Yasuj, Iran. Then DNA was extracted from these samples and used to determine the frequency of HLA‐DQ4/5 genotypes through Sequence‐Specific Primer‐Polymerase Chain Reaction assay. SPSS 20 was utilized for statistical analyses.

Fifty diagnosed patients with CD (high anti‐tissue transglutaminase [tTG]‐IgA level [upper limit of normal] with pathological findings of Marsh III) and 50 non‐CD individuals (normal anti‐tTG‐IgA level and normal total IgA level) were enrolled in the study from August 5, 2022 to October 15, 2023. Findings showed that the DQ4a*4b allele has the highest frequency in the CD samples (78%, p < 0.01) followed by the DQ5a*5b allele (12%, p < 0.01). Additionally, there was a higher prevalence of DQ4/DQ5 in patients with CD compared to controls (odds ratio = 6.5, confidence interval = 0.84 to 69.46, p < 0.01). Furthermore, a significant association was found among HLA DQ4/5 genotype, age (>9.5) (p < 0.01), and gender (female) (p < 0.05).

The observed significant differences among HLA‐DQ4 and HLA‐DQ5 in Iranian CD samples against controls and the high value of the relative risks showed the significant function of the studied alleles in the prevalence of CD in Iranian patients.