Association with <scp>HLA‐DRB1</scp> in Egyptian and German pemphigus vulgaris patients

Haase, Ozan; Alneebari, R.; El-Darouti, Mohammad Ali; Hady, Mohamed Abd El; Dorgham, Dina A.; El‐Nabarawy, Eman; Mahmoud, S. B. El Din; Sayed, H. Mosaad El; Darwish, Mohamed; Abbas, Fatma; Salah, S.; Mosaad, Youssef M.; El-Chennawi, Farha; Mongy, S. Al; Abdel-Aziz, Azza; Gaber, S. Abd El; Hertl, Michael; Eming, Rüdiger; Recke, Andreas; Möller, Steffen; Schmidt, Enno; Zillikens, Detlef; Ibrahim, Saleh M.

doi:10.1111/tan.12519

Cited by 14 publications

(12 citation statements)

References 11 publications

(12 reference statements)

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“…We also found that HLA‐DRB1*14:54 allelic frequency in our patients is higher compared to healthy Serbian population and that its carriage increases risk for PV, although statistical significance was lost upon correction. Having in mind that the alleles HLA‐DRB1*14:54 and a variant of HLA‐DRB1*14:01 ( DRB1*14:01:01 ) share the same amino acids within the antigen recognition site , we have analyzed combined frequency of those two alleles in our PV patients and donors and found a crude difference between cases and controls ( P = 0.0049). However, this loses significance after adjustment for multiple comparisons ( P adj = 0.133), data not shown.…”

Section: Discussionmentioning

confidence: 99%

Human leukocyte antigen class II (DRB1 and DQB1) alleles and haplotypes frequencies in patients with pemphigus vulgaris among the Serbian population

Živanović

Bojic

Medenica

et al. 2016

HLA

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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.

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Section: Discussionmentioning

confidence: 99%

Human leukocyte antigen class II (DRB1 and DQB1) alleles and haplotypes frequencies in patients with pemphigus vulgaris among the Serbian population

Živanović

Bojic

Medenica

et al. 2016

HLA

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“…Allele DRB1*04:06 in the Japanese and Chinese is a PV susceptibility allele as well (Yamashina et al, 1998;Zhang et al, 2019). In the DRB1*04 haplotypes, the association with DQA1*03:01-DQB1*03:02 seems secondary to the association with DRB1*04, as a result of high linkage disequilibrium (LD): The alleles DRB1*04:01, 04:03 and 04:05 (and other) also are inserted in DQA1*03:01-DQB1*03:02 haplotypes, but were not associated with increased susceptibility to PV (e.g., Carcassi et al, 1999;Haase et al, 2015). In fact, DRB1*04:01 may be a protective allele in the German population (Haase et al, 2015).…”

Section: Dsg3mentioning

confidence: 99%

“…In the DRB1*04 haplotypes, the association with DQA1*03:01-DQB1*03:02 seems secondary to the association with DRB1*04 , as a result of high linkage disequilibrium (LD): The alleles DRB1*04:01, 04:03 and 04:05 (and other) also are inserted in DQA1*03:01-DQB1*03:02 haplotypes, but were not associated with increased susceptibility to PV (e.g., Carcassi et al. , 1999; Haase et al. , 2015 ).…”

Section: Pemphigus Geneticsmentioning

confidence: 99%

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Beyond the HLA polymorphism: A complex pattern of genetic susceptibility to pemphigus

Petzl-Erler

2020

Genet. Mol. Biol.

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Pemphigus is a group of autoimmune bullous skin diseases that result in significant morbidity. As for other multifactorial autoimmune disorders, environmental factors may trigger the disease in genetically susceptible individuals. The goals of this review are to summarize the state of knowledge about the genetic variation that may affect the susceptibility and pathogenesis of pemphigus vulgaris and pemphigus foliaceus-both the endemic and the sporadic forms-, to compare and discuss the possible meaning of the associations reported, and to propose recommendations for new research initiatives. Understanding how genetic variants translate into pathogenic mechanisms and phenotypes remains a mystery for most of the polymorphisms that contribute to disease susceptibility. However, genetic studies provide a strong foundation for further developments in this field by generating testable hypotheses. Currently, results still have limited influence on disease prevention and prognosis, drug development, and clinical practice, although the perspectives for future applications for the benefit of patients are encouraging. Recommendations for the continued advancement of our understanding as to the impact of genetic variation on pemphigus include these partially overlapping goals: (1) Querying the functional effect of genetic variants on the regulation of gene expression through their impact on the nucleotide sequence of cis regulatory DNA elements such as promoters and enhancers, the splicing of RNA, the structure of regulatory RNAs and proteins, binding of these regulatory molecules to regulatory DNA elements, and alteration of epigenetic marks; (2) identifying key cell types and cell states that are implicated in pemphigus pathogenesis and explore their functional genomes; (3) integrating structural and functional genomics data; (4) performing disease-progression longitudinal studies to disclose the causal relationships between genetic and epigenetic variation and intermediate disease phenotypes; (5) understanding the influence of genetic and epigenetic variation in the response to treatment and the severity of the disease; (6) exploring gene-gene and genotype-environment interactions; (7) developing improved pemphigus-prone and non-prone animal models that are appropriate for research about the mechanisms that link genotypes to pemphigus. Achieving these goals will demand larger samples of patients and controls and multisite collaborations.

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“…O sistema HLA é objeto de estudo para identificar os alelos envolvidos na patogênese de diversas doenças, tais como estomatite aftoide recorrente, líquen plano, pênfigo vulgar, penfigoides e seus subtipos [71][72][73] .…”

Section: Sistema Hla Nas Populaçõesunclassified

Estudo da associação entre antígenos de histocompatibilidade leucocitária e penfigoide bolhoso em pacientes brasileiros

Chagury¹

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Association with HLA‐DRB1 in Egyptian and German pemphigus vulgaris patients

Cited by 14 publications

References 11 publications

Human leukocyte antigen class II (DRB1 and DQB1) alleles and haplotypes frequencies in patients with pemphigus vulgaris among the Serbian population

Human leukocyte antigen class II (DRB1 and DQB1) alleles and haplotypes frequencies in patients with pemphigus vulgaris among the Serbian population

Beyond the HLA polymorphism: A complex pattern of genetic susceptibility to pemphigus

Estudo da associação entre antígenos de histocompatibilidade leucocitária e penfigoide bolhoso em pacientes brasileiros

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