A gene dosage effect of the DQA1*0501/DQB1*0201 allelic combination influences the clinical heterogeneity of celiac disease.

This study reports the HLA-DR and DQ molecular characterization of 62 CD patients of Sardinian descent. Patients were divided in two groups (36 in group I and 26 in group II) according to the clinical features at the disease onset. Among the patients of group I, having the fully expressed form of CD and a mean age of 3 years at disease onset, a significant increase of DRB10301, DQA10501, DQB10201 homozygotes, encoding in cis two DQ (alpha 10501, beta 10201) susceptibility heterodimers, was observed when compared either with the patients of group II (pIII < 0.012) or with healthy individuals (pI < 10(-6)). On the other hand, in the patients of group II, presenting oligosymptomatic forms and a mean age of 5.7 years at the disease onset, the haplotype combinations encoding in cis or in trans only one DQ (alpha 10501, beta 10201) heterodimer were significantly increased in comparison either with the patients of group I (pIII < 0.026) or with controls (pII < 10(-6)). These findings suggest that a double dose of DQA10501, DQB10201 genes may predispose a person to an earlier onset and to more severe disease manifestations. Genotype analysis showed that only three patients (all in group I) failed to form in trans or in cis the DQ (alpha 10501, beta 10201) heterodimer and carried the DQA10101,DQB10501 haplotype, suggesting its possible role in CD susceptibility. In addition, a significant increment of DQB10501 gene (pc < 0.0065) was found comparing the frequency of DQB1 alleles in CD patients and healthy controls, after exclusion of DQB1*0201 chromosomes.(ABSTRACT TRUNCATED AT 250 WORDS)