The involvement of the HLA ‐ DQB 1 alleles in the risk and the severity of Iranian coeliac disease patients

Summary Coeliac disease ( CD ) is a highly prevalent autoimmune disorder that is triggered by the ingestion of wheat gluten and related proteins in genetically susceptible individuals. The CD is associated with human leucocyte antigen ( HLA ) genes particularly with HLA ‐ DQ alleles encoding HLA ‐ DQ 2 and DQ 8 proteins. To define risk and severity alleles for CD , a total of 120 definite CD patients and 100 healthy controls were genotyped for HLA ‐ DQB 1 gene. HLA ‐ DQB 1 genotyping was performed in all patients and controls using PCR ‐ SSP technique, and to evaluate the clinical relevance of testing for HLA ‐ DQB 1 and determining absolute risk of disease, prevalence‐corrected positive predictive value and prevalence‐corrected negative predictive value (Pc PPV and Pc NPV ) were calculated. Our results for a first time show that DQB 1*02:00 and DQB 1*03:02 alleles and DQB 1*02:01/03:02 genotype very significantly associated with increased risk of patients with CD , and DQB 1*03:01,4 allele provides protection against CD in Iranian patients. Furthermore, the Pc PPV for DQB *02:01 and 03:02 alleles in CD were 0.014 and 0.012, respectively, and the highest absolute risk presented by DQB *0201/0302 genotype (Pc PPV  = 0.079) and 98% of patients with CD carried DQB 1*02:01/x or DQB 1*03:02/x genotype. The results also clearly demonstrated that the DQB 1*02:01 allele significantly associated with severity of CD , while DQB 1*03:02 allele associated with mild form of CD . These results suggest that clinically suspected individuals for CD and first‐degree relatives of patients with CD to be screened for HLA ‐ DQB *0201 and DQB *0302 alleles for possible early diagnosis and treatments.