Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Drouet, M. et al.

HLA-DRB1 and HLA-DQB1 genes in susceptibility and resistance to cicatricial pemphigoid in French Caucasians.

Cicatricial pemphigoid (CP) is a chronic, autoimmune, subepithelial blistering disease, characterized by the presence of antibasement membrane antibodies (BMZ) against anchoring filaments components. An association between the HLA-DQB1*0301 allele and ocular cicatricial pemphigoid has been previously reported in North American Caucasians. In this study, we compared high resolution typing HLA-DRB1 and -DQB1 alleles in 25 CP patients (50 haplotypes) with 106 geographically matched, healthy controls (212 haplotypes), who were all French Caucasians. As in American Caucasians, we confirmed a positive association of CP with the HLA-DQB1*0301 allele which was present in 54% of CP haplotypes (27/50); by contrast 21.7% (46/212) of the matched normal individuals carried the DQB1*0301allele (Pc = 7 x 10(-5); RR = 4.23). HLA-DQB1*0301 is in linkage disequilibrium with several DRB1 alleles. Only the DRB1*1101 DQB1*0301 haplotype frequency was significantly increased (24.0% in CP, 6.6% in control, Pc = 0.002). Furthermore, we observed a decrease of the frequency of the DQB1*02 allele (6% vs 25% in the control group, Pc = 0.05; RR = 0.19). The negative association corresponds to a significant decreased frequency of the DRB1*0701 DQB1*0202 haplotype (0% in CP vs 12.7%, Pc = 0.07 PC) and a non-significant decrease of DRB1*0301 DQB1*0201 (4% in CP vs 12.3%). HLA-DQB1*0301 encodes a negative charge at position DQ 57 (Asp), a critical position in peptide binding to the HLA-DQ molecule groove and therefore we speculate that this molecule may play a role in the selection of BMZ peptides in CP.[1]

References

HLA-DRB1 and HLA-DQB1 genes in susceptibility and resistance to cicatricial pemphigoid in French Caucasians. Drouet, M., Delpuget-Bertin, N., Vaillant, L., Chauchaix, S., Boulanger, M.D., Bonnetblanc, J.M., Bernard, P. European journal of dermatology : EJD. (1998) [Pubmed]

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