E cadherin is an adhesive

E-cadherin is an adhesive Ca2+ dependent transmembrane protein mediating tight and strong cell-cell adhesion through homophilic interactions. There is strong evidence in favour of the major role of E-cadherin in melanocytes adhesion to keratinocytes in the Norfloxacin hydrochloride australia (Tang et al., 1994). The expression of E-cadherin in melanocytes in both non-segmental and segmental forms of vitiligo has been shown to be reduced similarly compared to normally pigmented skin emphasizing the cell adhesion defect theory as an initial step for pigment loss in vitiligo (Grill et al., 2018). DDR1 is a transmembrane tyrosine kinase receptor that forms a complex with E-cadherin at cell junctions and plays a physiological role through stabilization of E-cadherin and E-cadherin-mediated cell aggregation (Eswaramoorthy et al., 2010). The results of previous studies showed a significant reduction in DDR1 expression level in lesional compared to non-lesional vitiligo skin which adds to the cumulative evidence pointing to DDR1 as a major factor causing impaired adhesion process involved in vitiligo (Elgarhy et al., 2016; Reichert-Faria et al., 2013). Despite the substantial evidences in favour of the probable mutation of the CDH1 and DDR1 genes in vitiligo, there are not enough and comprehensive studies on the role of these polymorphisms so far, and the results of the previous studies have not been conclusive (Birlea et al., 2011; Kim et al., 2010; Silva de Castro et al., 2010; Tarlé et al., 2015). Therefore, the present study was designed to assess the association between the risk of developing vitiligo and single nucleotide polymorphisms (SNP) in two important genes involved in the regulation of melanocyte adhesion including CDH1 and DDR1.
Materials and methods
Results
Discussion The findings of previous studies conducted in recent years have identified vitiligo as a complex, multifactorial and polygenic disease; however, only a few genes have been shown to be consistently and functionally associated with the development of the disease (Tarlé et al., 2014). The pathogenesis of vitiligo has not been completely determined, but regardless of the intrinsic pathomechanism, the presence of the extrinsic pathomechanism including mechanical trauma is necessary for explaining the induction of chronic epidermal melanocyte loss (Gauthier et al., 2003). It has also been suggested that a mechanical detachment of melanocytes followed by trans epidermal elimination is the probable explanation for the mechanism of the depigmentation observed during the mechanical friction (Gauthier et al., 2003). The weaker expression of the two main proteins adhering melanocytes to the epidermis basal layer, E-cadherin and DDR1, has been implicated as one of the aggravating factors in the loss of melanocytes (Kim and Lee, 2010; Ricard et al., 2012). The E-cadherin gene (CDH1) is located on chromosome 16q22.1 and the protein consists of a large extracellular domain consisting of smaller transmembrane and cytoplasmic domains and five repeat domains (Ringwald et al., 1987). Tarle et al. in their family-based and case-control study conducted in Brazil, found an association between the risk of developing vitiligo and CDH1 (rs10431924) polymorphism. They found a positive association between the risk of developing vitiligo and the T allele of the CDH1 gene; they showed that the effect was particularly evident in the presence of autoimmune comorbidities (Tarlé et al., 2015). In contrast, the results of the present study revealed the association between the risk of developing vitiligo and the CDH1 CC genotype, and the association was observed at the CDH1 genotype rather than allelic level. These contradictory results might be attributed to the ethnic differences or different clinical characteristics related to the study populations. The results of stratified analysis in the current study revealed a significant correlation between the CDH1 CC genotype and late age of onset, clinical type of vitiligo, the absence of autoimmune comorbidities and family history of autoimmune disorders. There was also an allelic association between the CDH1 C allele and both late age of onset and family history of autoimmune disorders. In the study conducted on Brazilian population, the researchers have not evaluated the above-mentioned relationships, and this may have led to the contradiction of the results.