Assessment of distribution of human leukocyte antigen-DQ risk genotyping among cases of clinically suspected celiac disease: A descriptive observational study

Abstract Background: Celiac disease is an immune-mediated enteropathy triggered by gluten ingestion in genetically susceptible individuals. Human leukocyte antigen (HLA)-DQ genotypes, particularly HLA-DQ2.5 and HLA-DQ8, are recognized as major genetic determinants of disease susceptibility. Evaluating HLA-DQ status in clinically suspected cases may aid in early diagnosis, especially where serology or histopathology is inconclusive. Objective: To determine the frequency and distribution of HLA-DQ genotypes among clinically suspected celiac disease patients and to assess their association with demographic, clinical, and serological characteristics. Materials and Methods: A hospital-based descriptive observational study was conducted on 204 newly suspected celiac disease patients. Clinical profiles, hematological parameters, and immunoglobulin A (IgA) anti-endomysial antibodies (IgA-EMA) results were recorded. Genomic DNA extracted from peripheral blood was analyzed for HLA-DQ2.5, DQ2, DQ8, and combined genotypes using allele-specific polymerase chain reaction. Statistical correlations were examined between HLA genotypes and age, sex, serology, and family history. Results: HLA-DQ2.5 (DRB1 * 03–DQA1 * 05:01–DQB1 * 02:01) was the predominant allele, observed in 37.3% of patients, followed by HLA-DQ8 in 15.2% and isolated DQ2 in 12.3%. Combined genotypes (DQ2.5/DQ2, DQ2.5/DQ8, and DQ2/DQ8) were present in smaller proportions. DQ2.5 was significantly associated with patients aged <30 years ( P = 0.031), suggesting earlier phenotypic expression in genetically predisposed individuals. A significant association was also noted between DQ2.5 and tTG-IgA positivity ( P = 0.043), indicating alignment between genetic susceptibility and autoimmune serological response. No statistically significant association was observed between HLA genotype and family history. Conclusion: HLA-DQ2.5 is the predominant genetic susceptibility marker among clinically suspected celiac disease patients and shows significant association with younger age and positive tTG-IgA serology. HLA typing is particularly useful as an exclusion tool and enhances diagnostic accuracy when integrated with clinical and serological assessment.