CDH1 and DDR1 common variants confer risk to vitiligo and autoimmune comorbidities

Abstract

The weaker expression of the two main proteins adhering melanocytes to the epidermis basal layer, Epithelial Cadherin (E-cadherin) and Discoidin Domain Receptor Tyrosine kinase 1 (DDR1), has been implicated as one of the aggravating factors in the loss of melanocytes in vitiligo. The present study was designed to assess the association between single nucleotide polymorphisms (SNP) in the genes encoding these proteins, CDH1 and DDR1, and the risk of developing vitiligo. The independent case-control study was conducted on the sample including152 patients with vitiligo and 152 matched controls. A questionnaire was completed for recording demographic and clinical characteristics of vitiligo patients. Venous blood samples were taken from all the subjects. Genotype frequencies were determined for CDHI C/T (rs 10431924) and DDRI A/C (rs 2267641) genes polymorphisms using polymerase chain reaction (PCR) amplification method and Restriction Fragment Length Polymorphism (RFLP) analysis. The CDH1 CC genotype was found to be significantly associated with the risk of developing vitiligo. The results of stratified analysis revealed a correlation between CDH1 CC genotype and late age of onset, clinical type of vitiligo, the absence of autoimmune comorbidities and family history of autoimmune disorders. However, the expression level of CDH1 TT genotype increased significantly in patients with autoimmune comorbidities. There was also a significant relationship between the DDR1 CC genotype and the risk of developing vitiligo. The results of stratified analysis revealed a correlation between DDR1 CC genotype and early age of onset, clinical type of vitiligo and absence of family history of autoimmune disorders. The findings of the study confirm the conjecture previously made in the literature regarding the melanocytes' adhesion deficit as an initial step for pigment loss in vitiligo and emphasize the substantial role of friction and koebner phenomenon in the pathogenesis of vitiligo. Moreover, a probable association can be proposed between the adhesion deficit involved in vitiligo and autoimmune disorders.

Keywords: Adhesion deficit; Koebner; Pigment loss; SNP; Vitiligo genetic.