title: HLA-DRB1*0402 haplotypes without DQB1*0302 in Venezuelan patients with pemphigus vulgaris.
abstract: The two basic forms of autoimmune intraepidermal blistering diseases, pemphigus vulgaris (PV) and pemphigus foliaceus (PF), affect different layers of the skin, have different symptoms and target different antigens. We have defined human leukocyte antigen (HLA)-DRB1-DQB1 alleles and haplotypes in a case-control study of 66 non-Jewish patients attending a public reference Hospital over the past 10 years. The control group consisted of 101 matched individuals tested also by medium to high-resolution polymerase chain reaction-sequence-specific oligonucleotide with primers and probes from the 12th and 13th International Histocompatibility Workshop. Patients and controls were descendants of three-generation individuals born in the country. Among the patients, 49 had PV, 50% showed predominantly mucosal involvement, 50% showed predominantly the cutaneous clinical phenotype and 17 had PF. Statistically significant HLA-DR frequency differences between patients with PV and controls were found only for DRB1*0402 and DRB1*1401 [odds ratio (OR) = 27.22, confidence interval (CI) 94.7-7.82, P= 1.1 x 10(-14) and OR = 46.56, CI 801.4-2.70 P= 7.5 x 10(-6), respectively]. Both alleles were also increased in the patients with PF compared with the controls (OR = 7.0, P= 0.038 and OR = 21.64, P= 0.009, respectively), but the significance of the difference did not resist Bonferroni correction. Haplotype analysis showed that DRB1*0402 was always present with DQB1*0302 and DRB1*1401 with DQB1*0503, but no independent effect of the DQB1*0302 in the former haplotype was evident. Our results support the hypothesis that the DRB1*0402 without DQB1*0302 is the most relevant HLA-DRB1 allele responsible for the pathogenesis of pemphigus in Venezuelan patients with PV and discard the DQB1*0302 influence observed in other populations.
authors: Facultad de Medicina, Hospital Universitario de Caracas, Universidad Central de Venezuela, Caracas, Venezuela.
authors: A M
authors: AM
authors: Sáenz-Cantele
authors: M
authors: M
authors: Fernández-Mestre
authors: S
authors: S
authors: Montagnani
authors: A
authors: A
authors: Calebotta
authors: O
authors: O
authors: Balbas
authors: Z
authors: Z
authors: Layrisse
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006683:HLA-DQ Antigens / Q000235:genetics*; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D010392:Pemphigus / Q000208:ethnology / Q000235:genetics*; D011446:Prospective Studies; D014687:Venezuela
chemical_list: D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C553506:HLA-DRB1*04:02 antigen