Molecular Genetic of Atopic dermatitis: An Update

Abstract

Atopic dermatitis (AD) is a chronic multifactorial inflammatory skin disease. The pathogenesis of AD remains unclear, but the disease results from dysfunctions of skin barrier and immune response, where both genetic and environmental factors play a key role. Recent studies demonstrate the substantial evidences that show a strong genetic association with AD. As for example, AD patients have a positive family history and have a concordance rate in twins. Moreover, several candidate genes have now been suspected that play a central role in the genetic background of AD. In last decade advanced procedures similar to genome-wide association (GWA) and single nucleotide polymorphism (SNP) have been applied on different population and now it has been clarified that AD is significantly associated with genes of innate/adaptive immune systems, human leukocyte antigens (HLA), cytokines, chemokines, drug-metabolizing genes or various other genes. In this review, we will highlight the recent advancements in the molecular genetics of AD, especially on possible functional relevance of genetic variants discovered to date.

Keywords: Atopic dermatitis; chemokine; cytokine; drug-metabolizing genes; immune genes; molecular genetics.

Figure 1. Cleavage of profilaggrin into natural moisturizing factors via degradation of filagrgrin molecules

Filagrgrin is involved in the development of keratinocytes to maintain epidermal integrity and it is an important marker of keratinocytes differentiation. (after Kabashima, 2013 ⁽⁹⁾).

Figure 2. Identified candidate genes in atopic dermatitis

FLG, Filaggrin; SPINK5, Serine Protease Inhibitor Kazal-Type 5 ; MHC, major histocompatibility complex; HLA, human leukocyte antigen; CARD4, Caspase recruitment domain-containing protein 4; NOD, nucleotide binding oligomerization domain protein; CD, cluster of differentiation; MBL2, mannose binding lectin-2; TLR, toll like receptor; DEFB1, human defernsin 1; IL, interleukin; IL-4Rα, interleukin 4 receptor alpha; STAT6, signal transducer and activator of transcription-6; TNF, tumor necrosis factor; IFNγ, interferon gamma; IL1RN, interleukin 1 receptor antagonist; ST2, suppression of tumorigenicity-2; TGF, transforming growth factor; GM-CSF, granulocyte macrophage colony stimulating factor; CCL, chemokine C-motif ligand; CCR, chemokine C motif receptor; CMA1; mast cell chymase 1; GSTP1, clutathionine S-transferase P1; NAT, N-acetyl transferase; CTLA4, cytotoxic T-lymphocyte associated antigen-4; KLK, kallikrein; RUNX1, runt-related transcription factor 1; TRF-2, interferon regulatory factor 2; FCER1B, high affinity IgE receptor beta chain; PHF11, plant homeodomain zink finger 11 protein 11.