<i>TRAF1</i>/<i>C5</i>polymorphism is not associated with pemphigus

Mejri, K.; Mbarek, Hamdi; Kallel-Sellami, M.; Petit-Teixeira, Élisabeth; Abida, Olfa; Zitouni, M.; Ayed, M. Ben; Mokni, M.; Fezza, B.; Turki, H.; Tron, François; Gilbert, Danièle; Masmoudi, Hatem; Prum, Bernard; Cornélis, François; Makni, S.

doi:10.1111/j.1365-2133.2009.09136.x

Cited by 5 publications

(4 citation statements)

References 9 publications

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“…By contrast, individuals with rs700218 * A (intron 1 of C9 ) were more protected (OR = 0.12; p = 0.0471). We found no association with C5 polymorphisms, as reported by others (who investigated only one SNP) ( 99 ). Nevertheless, individuals with the rs10404456 * C allele (located in the 5′ UTR of the C5AR1 gene and associated with decreased mRNA levels in sun-exposed skin) ( 83 ) presented increased susceptibility to PF (OR = 1.43 p = 0.0155).…”

Section: The Long Known Versus the Unexpected: Complement In Pfsupporting

confidence: 70%

Sparking Fire Under the Skin? Answers From the Association of Complement Genes With Pemphigus Foliaceus

et al. 2018

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Skin blisters of pemphigus foliaceus (PF) present concomitant deposition of autoantibodies and components of the complement system (CS), whose gene polymorphisms are associated with susceptibility to different autoimmune diseases. To investigate these in PF, we evaluated 992 single-nucleotide polymorphisms (SNPs) of 44 CS genes, genotyped through microarray hybridization in 229 PF patients and 194 controls. After excluding SNPs with minor allele frequency <1%, out of Hardy–Weinberg equilibrium in controls or in strong linkage disequilibrium (r2 ≥ 0.8), 201 SNPs remained for logistic regression. Polymorphisms of 11 genes were associated with PF. MASP1 encodes a crucial serine protease of the lectin pathway (rs13094773: OR = 0.5, p = 0.0316; rs850309: OR = 0.23, p = 0.03; rs3864098: OR = 1.53, p = 0.0383; rs698104: OR = 1.52, p = 0.0424; rs72549154: OR = 0.55, p = 0.0453). C9 (rs187875: OR = 1.46, p = 0.0189; rs700218: OR = 0.12, p = 0.0471) and C8A (rs11206934: OR = 4.02, p = 0.0323) encode proteins of the membrane attack complex (MAC) and C5AR1 (rs10404456: OR = 1.43, p = 0.0155), a potent anaphylatoxin-receptor. Two encode complement regulators: MAC-blocking CD59 (rs1047581: OR = 0.62, p = 0.0152) and alternative pathway-blocking CFH (rs34388368: OR = 2.57, p = 0.0195). One encodes opsonin: C3 (rs4807895: OR = 2.52, p = 0.0239), whereas four encode receptors for C3 fragments: CR1 (haplotype with rs6656401: OR = 1.37, p = 0.0382), CR2 (rs2182911: OR = 0.23, p = 0.0263), ITGAM (CR3, rs12928810: OR = 0.66, p = 0.0435), and ITGAX (CR4, rs11574637: OR = 0.63, p = 0.0056). Associations reinforced former findings, regarding differential gene expression, serum levels, C3, and MAC deposition on lesions. Deregulation of previously barely noticed processes, e.g., the lectin and alternative pathways and opsonization-mediated phagocytosis, also modulate PF susceptibility. The results open new crucial avenues for understanding disease etiology and may improve PF treatment through additional therapeutic targets.

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Section: The Long Known Versus the Unexpected: Complement In Pfsupporting

confidence: 70%

Sparking Fire Under the Skin? Answers From the Association of Complement Genes With Pemphigus Foliaceus

et al. 2018

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“…The SNP rs10818488 is an eQTL for different genes and could have a functional impact on C5 synthesis. Even so, this regulatory intergenic SNP was not associated with PF and PV in the Tunisian population (Mejri et al, 2009). In line with this result, C5 polymorphisms were also not associated with FS (Bumiller-Bini et al, 2018).…”

Section: Genetics Sheds Light On the Controversial Relevance Of The Csupporting

confidence: 61%

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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“…However, while another study showed a positive association of TNFa (À308 G/A) promoter gene polymorphism with sporadic PF [7]. Our previous study showed no significance between the disease and the rs10818488 G/A, located in the intergenic region between the complement C5 and TRAF1 gene ''TNF receptor associated factor'' gene, nor with the C5 sera levels which could strengthen the secondary role of complement in the PF [8].…”

Section: Introductionmentioning

confidence: 58%

Polymorphisms of HLA microsatellite marker in Tunisian pemphigus foliaceus

et al. 2013

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TRAF1/C5polymorphism is not associated with pemphigus

Abstract: gene. High prevalence of the carrier state was also observed. We therefore recommend genetic counselling in communities where AE is observed and advocate increased awareness of possible variable phenotypic expressions.

Cited by 5 publications

References 9 publications

Sparking Fire Under the Skin? Answers From the Association of Complement Genes With Pemphigus Foliaceus

Sparking Fire Under the Skin? Answers From the Association of Complement Genes With Pemphigus Foliaceus

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

Polymorphisms of HLA microsatellite marker in Tunisian pemphigus foliaceus

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