Molecular Genetic Mechanisms of Chronic Urticaria

Abstract

Chronic urticaria (CU) is a common allergic skin disease that requires long-term pharmacological treatment. Some patients with severe CU suffer a poor quality of life. Although the pathogenic mechanisms of CU are not clearly understood, several groups have suggested that genetic mechanisms are involved in various CU cohorts. To further understand the molecular genetic mechanisms of CU, we summarize recent genetic data in this review. Although a few HLA alleles were suggested to be candidate markers in different ethnic groups, further replication studies that apply the recent classification are needed. Genetic polymorphisms in histamine-related genes, including FcεRI and HNMT, were suggested to be involved in mast cell activation and histamine metabolism. Several genetic polymorphisms of leukotriene-related genes, such as ALOX5, LTC4S, and the PGE2 receptor gene PTGER4, were suggested to be involved in leukotriene overproduction, a pathogenic mechanism. Further investigations using candidate gene approaches and genome-wide association studies (GWAS) will provide new insights into the molecular genetic mechanisms of CU, which will provide new marker genes for differentiation of CU phenotypes and identification of potential therapeutic targets.

Identification of phenotypic clusters of nonsteroidal anti-inflammatory drugs exacerbated respiratory disease

“…As mechanisms for neutrophil activation are not completely understood in NERD, further studies on anti‐IL17 antibody may be needed to control neutrophilic inflammation . Atopy is a predisposing factor for adult asthma and aspirin‐induced urticaria . In the present study, the atopy rate and the total IgE level were higher in subtype 1 (100%) than in subtype 2.…”

Urticária Crónica - Do Diagnóstico ao Tratamento

“…polimorfismos nos genes da resposta imuno-inflamatória). 22 Agonistas não imunológicos como a substância P, endorfinas, encefalinas, péptidos endógenos, somatostatina, fatores exógenos como fármacos (codeína, AINEs), alimentos ou aditivos alimentares (ácido benzóico, salicilatos, etc.) ou estímulos locais (frio, pressão, entre outros) podem também induzir libertação de mediadores pró-inflamatórios pelos mastócitos.…”

“…1,2,22 Não sendo específico para a UCE, o TSA corrobora a origem endóge-na/auto-reativada urticária, e poderá ser um indicador de uma doença de maior duração, gravidade e refratária às terapêuticas de 1ª e 2ª linha. 24,25 Embora não validado e efetuado em raros centros, o teste de ativação dos basó-filos (TAB) por citometria de fluxo tem demonstrado utilidade no diagnóstico de auto reatividade em doentes com UCE.…”

C‐reactive protein (CRP) rs3093059C predicts poor mizolastine response in chronic spontaneous urticaria patients with elevated serum CRP level

“…[28] It is reported that gene variants also have an impact on treatment outcomes. [29,30] According to our previous studies, both C5AR rs11673309 and ORAI1 rs3741595 were associated with the efficacy of the non-sedating H1 antihistamine desloratadine. [31,32] Among patients treated with levocetirizine, researchers observed that the elevated CRP level was associated with poor response and CRP polymorphisms affected the serum CRP level.…”