A study of Italian pediatric celiac disease patients confirms that the primary HLA association is to the DQ(α1 ∗0501, β1 ∗0201) heterodimer

Abstract

Celiac disease (CD) has been recently reported to be primarily associated with the DQ(α1 ∗0501, β1 ∗0201) heterodimer encoded in cis on DR3 haplotype and in trans in DR5, 7 heterozygous individuals. The high incidence of DR5, 7 heterozygotes, reflecting the high frequency of the DR5 allele in Italy, makes the analysis of the Italian CD patients critical. Polymerase chain reaction-amplified DNA from 50 CD patients and 50 controls, serologically typed for DR and DQw antigens, was hybridized with five DQA1-specific oligonucleotide probes detecting DQA1 ∗0101 + 0102 + 0103, DQA1 ∗0201, DQA1 ∗0301 + 0302, DQA1 ∗0401 + 0501 and DQA1 ∗0501 and a DQB1-sequence-specific oligonucleotide probe recognizing DQB1 ∗0201 allele. As expected by the DR-DQ disequilibria, DQA1 ∗0201 [62% in patients versus 26% in controls, relative risk (RR) = 5] and DQA1 ∗0501 (96% versus 56%, RR = 19) show positive association with the disease. Of CD patients, 92% (50% DR3 and 42% DR5,7) compared to 18% of the controls carry both DQA1 ∗0501 and DQB1 ∗0201 alleles, so that the combination confers an RR of 52, higher than both the risks of the single alleles ( DQA1 ∗0501 RR = 19, DQB1 ∗ 0201 RR = 30 ), confirming the primary role of the dimer in determining genetic predisposition to CD both in DR3 and in DR5, 7 subjects.