{'fraction_non_alphanumeric': 0.04186276938320535, 'fraction_numerical': 0.02997275204359673, 'mean_word_length': 5.25077399380805, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
HLA-DRB1*04:02, DRB1*08:04 and DRB1*14 alleles associated to pemphigus vulgaris in southeastern Brazilian population.

We report here for the first time a strong association of the DRB1*08:04 allele and pemphigus vulgaris (PV) in a Brazilian highly admixed cohort. The authors recently performed a prospective case–control study, including 36 unrelated patients with PV from São Paulo, Brazil. All patients were diagnosed according to the standard criteria: (i) clinical features: a mucocutaneous blistering disorder; (ii) histopathology: a skin or a mucosal biopsy showing suprabasal acantholysis and clefting; and (iii) immunopathology: direct or indirect immunofluorescence to show IgG antibodies that bind to the intercellular spaces of the epidermis (1). Patients with neoplasia or paraneoplastic pemphigus (2) were not included. All patients were non-Jewish, and all except one patient had both parents and grandparents born in Brazil. DNA extraction was performed using the DTAB/CTAB method (3). Human leukocyte antigen (HLA) typing at the DRB1 locus was performed after DNA extraction using polymerase chain reaction (PCR) amplification with sequence-specific oligonucleotides (PCR-SSO) using LABType kits (One Lambda, Inc., Canoga Park, CA) (4, 5). HLA phenotypes were assigned to each individual based on the oligotyping results. Phenotypic and allelic frequencies were compared with those from a collected DNA bank of healthy volunteers donors registered in the national registry of bone marrow donors (REDOME) (6) from Sao Paulo, typed in the same laboratory between January 2008 and April 2009 using the same methods. One hundred sixty-two unrelated individuals were randomly chosen from the data bank (preserving the same ethnicity proportions of study group) and formed the control group. The allele frequencies found in the control group were similar to those reported by previous studies in samples of population from southeastern Brazil (7–9). Unlike other researchers, the authors of this study decided to not select individuals – cases or controls – from a homogeneous ethnic group, based on the premise that the Brazilian population is one of the most heterogeneous populations in the world as a result of five centuries of admixture between Europeans, Africans, and Amerindians, which produces, at the individual level, a significant dissociation of color and genomic ancestry (10). Moreover, evidence shows that the possible effect of population stratification is likely to be small in most situations and decreases as the number of admixed ethnicities increases (11, 12). Two-tailed Fisher’s exact test was used to detect significant deviations in allele frequency from controls; a P value ≤0.05 was considered a significant result. Odds ratios (OR) were calculated by the Woolf method (13) (or by the modified method described by Haldane (14)). Statistical analysis was performed using spss for Mac version 16.0 (SPSS Inc, Chicago, IL). A correction for multiple testing with the false discovery rate method (15, 16) was applied after the identification of alleles in PV patients displaying significant deviation in frequency from controls. The distribution of DRB1 genotypes in the patients and the controls was in Hardy–Weinberg equilibrium for patients (P = 0.82876) and for the controls (P = 0.83123). After correction for multiple comparisons, the null hypothesis was rejected for the association of PV with the alleles DRB1*04:02, DRB1*08:04, and DRB1*14, with OR (confidence interval 95%) 44.6 (19.2–103), 18.6 (8.3–41.7), and 4.8 (2.2–10.4), respectively. The authors report here for the first time a strong association of the DRB1*08:04 allele and PV in a Brazilian highly admixed cohort. Previous studies may have failed to identify this association because they did not include populations that have individuals of African origins. High-resolution typing of nearby loci DQA1 and DQB1 is necessary to differentiate if the association is inherent to the HLA-DRB1*08:04 allele or to a specific haplotype.