Celiac Disease Risk Allele Frequencies in San Luis (Argentina) and Evaluation of a Saliva Direct PCR Genotyping Approach

Celiac disease (CD) is strongly associated with specific HLA-DQ heterodimers, formed by HLA-DQA1 and HLA-DQB1 proteins. In particular DQ2.5 (DQB1*02 associated to DQA1*05) and DQ8 (DQB1*03:02 with DQA1*03) are present in virtually all celiac patients. HLA-DQB1*02 is considered the main single genetic susceptibility marker and has been reported in 90–95% of CD patients. However, the distribution of these alleles may vary across populations, potentially impacting the performance of genetic screening strategies. In this study, we evaluated the prevalence of HLA-DQ2.5 and DQ8 genotypes in celiac patients (n = 41) and an unbiased general population cohort (n = 60) from San Luis, Argentina, using a PCR-based genotyping approach. In addition, we assessed the feasibility of a simplified saliva direct PCR protocol for large-scale testing. Overall, 95.1% of CD patients carried DQ2.5 and/or DQ8. Notably, 41.5% of patients were DQ8(+)/DQ2.5(−), and 36.6% lacked the DQB1*02 allele, indicating that DQB1*02-based screening alone would have reduced sensitivity in this population. In the general population, 53.3% of individuals carried CD-associated genotypes, with a markedly higher prevalence of DQ8 compared to European cohorts. Genotype distributions deviated from Hardy–Weinberg equilibrium in CD patients but not in the general population. We show that DQB1*03:02 is a reliable proxy for DQ8, allowing simplification of genotyping strategies, whereas DQA1*05 typing remains essential to discriminate DQ2.5 from other lower-risk DQB1*02 carrying heterodimers. We also describe a saliva direct PCR approach showing a performance comparable to purified DNA-based assays. These findings highlight the importance of population-specific genetic data for optimizing CD screening strategies and foster the development of simplified, cost-effective genotyping approaches for large-scale applications.