title: Human leukocyte antigen class II (DRB1 and DQB1) alleles and haplotypes frequencies in patients with pemphigus vulgaris among the Serbian population.
abstract: The etiology of pemphigus vulgaris (PV) is multifactorial and includes genetic, environmental, hormonal, and immunological factors. Inheritance of certain Human class II leukocyte antigen (HLA) alleles is by far the best-established predisposing factor for the development of PV. Class II HLA alleles vary among racial/ethnic backgrounds. We have determined an association between HLA class II alleles and PV among the Serbian population. A total of 72 patients with confirmed diagnosis of PV were genotyped for HLA class II alleles. HLA frequencies were compared with unrelated healthy bone marrow donors. The statistical significance of differences between patients and controls was evaluated using Fisher's exact test. The DRB1*04 and DRB1*14 allelic groups were associated with PV (P adj = 4.45 × 10(-13) and 4.06 × 10(-19) respectively), while HLA-DRB1*11 was negatively associated with PV (P adj = 0.0067) suggesting a protective role. DRB1*04:02, DRB1*14:04, DQB1*03:02 and DQB1*05:03 alleles were shown to be strongly associated with PV (P adj = 1.63 × 10(-12), 5.20 × 10(-7), 1.28 × 10(-6), and 4.44 × 10(-5), respectively). The frequency of HLA DRB1*04-DQB1*03 and HLA DRB1*14-DQB1*05 haplotypes in PV patients was significantly higher than in controls (31.3% vs 8.8%, P adj =7.66 × 10(-8) and 30.6% vs 6.3%, P adj = 3.22 × 10(-10), respectively). At high-resolution level, statistical significance was observed in HLA-DRB1*04:02-DQB1*03:02 and HLA-DRB1*14:04-DQB1*05:03 haplotypes (P adj = 5.55 × 10(-12), and P adj = 3.91 × 10(-6), respectively). Our findings suggest that HLA-DRB1*04:02, DRB1*14:04, HLA-DQB1* 03:02 and DQB1*05:03 alleles and HLA-DRB1*04:02-DQB1*03:02 and HLA-DRB1*14:04-DQB1*05:03 haplotypes are genetic markers for susceptibility for PV, while DRB1*11 allelic group appears protective in Serbian population.
authors.affiliation: Clinic of Dermatovenereology, Clinical Center of Serbia, Belgrade, Serbia.
authors.forename: D
authors.initials: D
authors.lastname: Zivanovic
authors.affiliation: Faculty of Biology, University of Belgrade, Belgrade, Serbia.
authors.forename: S
authors.initials: S
authors.lastname: Bojic
authors.affiliation: Clinic of Dermatovenereology, Clinical Center of Serbia, Belgrade, Serbia.|Department of Dermatovenereology, School of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: L
authors.initials: L
authors.lastname: Medenica
authors.affiliation: Tissue Typing Department, Blood Transfusion Institute of Serbia, Belgrade, Serbia.
authors.forename: Z
authors.initials: Z
authors.lastname: Andric
authors.affiliation: Institute of Microbiology and Immunology, School of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: D
authors.initials: D
authors.lastname: Popadic
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D059866:HLA-DQ beta-Chains / Q000235:genetics*; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010392:Pemphigus / Q000235:genetics* / Q000276:immunology*; D055771:Serbia; D055815:Young Adult
chemical_list: D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D059811:HLA-DRB1 Chains
keywords: HLA class II alleles; HLA haplotypes; Pemphigus vulgaris