Dataset Information

Identification of two novel bullous pemphigoid- associated alleles, HLA-DQA105:05 and -DRB107:01, in Germans.

ABSTRACT: Bullous pemphigoid (BP) is the most common autoimmune skin blistering disease characterized by autoimmunity against the hemidesmosomal proteins BP180, type XVII collagen, and BP230. To elucidate the genetic basis of susceptibility to BP, we performed the first genome-wide association study (GWAS) in Germans. This GWAS was combined with HLA locus targeted sequencing in an additional independent BP cohort. The strongest association with BP in Germans tested in this study was observed in the two HLA loci, HLA-DQA1*05:05 and HLA-DRB1*07:01. Further studies with increased sample sizes and complex studies integrating multiple pathogenic drivers will be conducted.

SUBMITTER: Schwarm C

PROVIDER: S-EPMC8136166 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Identification of two novel bullous pemphigoid- associated alleles, HLA-DQA105:05 and -DRB107:01, in Germans.

Schwarm Christian C Gola Damian D Holtsche Maike M MM Dieterich Anabelle A Bhandari Anita A Freitag Miriam M Nürnberg Peter P Toliat Mohammad M Lieb Wolfgang W Wittig Michael M Franke André A Worm Margitta M Sticherling Michael M Ehrchen Jan J Günther Claudia C Gläser Regine R Peitsch Wiebke K WK Sárdy Miklós M Eming Rüdiger R Hertl Michael M Benoit Sandrine S Goebeler Matthias M Pföhler Claudia C Kunz Manfred M Kreuter Alexander A van Beek Nina N Erdmann Jeanette J Busch Hauke H Zillikens Detlef D Sadik Christian D CD Hirose Misa M König Inke R IR Schmidt Enno E Ibrahim Saleh M SM

Orphanet journal of rare diseases 20210519 1

Bullous pemphigoid (BP) is the most common autoimmune skin blistering disease characterized by autoimmunity against the hemidesmosomal proteins BP180, type XVII collagen, and BP230. To elucidate the genetic basis of susceptibility to BP, we performed the first genome-wide association study (GWAS) in Germans. This GWAS was combined with HLA locus targeted sequencing in an additional independent BP cohort. The strongest association with BP in Germans tested in this study was observed in the two HL ...[more]

PMID: 34011352

Similar Datasets

Project description:Bullous pemphigoid (BP) is the most prevalent autoimmune skin blistering disease and is characterized by the generation of autoantibodies against the hemidesmosomal proteins BP180 (type XVII collagen) and BP230. Most intriguingly, BP is distinct from other autoimmune diseases because it predominantly affects elderly individuals above the age of 75 years, raising the question why autoantibodies and the clinical lesions of BP emerges mostly in this later stage of life, even in individuals harboring known putative BP-associated germline gene variants. The mitochondrial genome (mtDNA) is a potential candidate to provide additional insights into the BP etiology; however, the mtDNA has not been extensively explored to date. Therefore, we sequenced the whole mtDNA of German BP patients (n = 180) and age- and sex-matched healthy controls (n = 188) using next generation sequencing (NGS) technology, followed by the replication study using Sanger sequencing of an additional independent BP (n = 89) and control cohort (n = 104). While the BP and control groups showed comparable mitochondrial haplogroup distributions, the haplogroup T exhibited a tendency of higher frequency in BP patients suffering from neurodegenerative diseases (ND) compared to BP patients without ND (50%; 3 in 6 BP with haplogroup T). A total of four single nucleotide polymorphisms (SNPs) in the mtDNA, namely, m.16263T>C, m.16051A>G, and m.16162A>G in the D-loop region of the mtDNA, and m.11914G>A in the mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 4 gene (MT-ND4), were found to be significantly associated with BP based on the meta-analysis of our NGS data and the Sanger sequencing data (p = 0.0017, p = 0.0129, p = 0.0076, and p = 0.0132, respectively, Peto's test). More specifically, the three SNPs in the D-loop region were negatively, and the SNP in the MT-ND4 gene was positively associated with BP. Our study is the first to interrogate the whole mtDNA in BP patients and controls and to implicate multiple novel mtDNA variants in disease susceptibility. Studies using larger cohorts and more diverse populations are warranted to explore the functional consequences of the mtDNA variants identified in this study on immune and skin cells to understand their contributions to BP pathology.

Dataset Information

Identification of two novel bullous pemphigoid- associated alleles, HLA-DQA105:05 and -DRB107:01, in Germans.

Publications

Identification of two novel bullous pemphigoid- associated alleles, HLA-DQA105:05 and -DRB107:01, in Germans.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Identification of two novel bullous pemphigoid- associated alleles, HLA-DQA1*05:05 and -DRB1*07:01, in Germans.

Publications

Identification of two novel bullous pemphigoid- associated alleles, HLA-DQA1*05:05 and -DRB1*07:01, in Germans.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Identification of two novel bullous pemphigoid- associated alleles, HLA-DQA105:05 and -DRB107:01, in Germans.

Identification of two novel bullous pemphigoid- associated alleles, HLA-DQA105:05 and -DRB107:01, in Germans.