Assessment of Gap Junction Protein Beta-2 rs3751385 Gene Polymorphism in Psoriasis Vulgaris

Abstract

Background Gap junction protein beta 2 (GJB2) upregulation in psoriasis transcriptome analysis as well as connexin 26 (Cx26, encoded by GJB2) expression upregulation in psoriatic plaques has already been substantiated. GJB2 rs72474224 and rs3751385 have been correlated with psoriasis vulgaris incidence in Chinese populations. Here we study the effect of rs3751385 in patients suffering from psoriasis vulgaris in a Caucasian Greek population at the prefecture of Thrace in Northern Greece. Methods One hundred and seventy-three (111 males and 62 females) psoriatic patients (108 were of early-onset psoriasis) and 171 matched controls were included in the study. Genomic DNA was extracted from peripheral blood leukocytes and genotyping was carried out by polymerase chain reaction-restriction-fragment length polymorphism (PCR-RFLP). Results A statistically significant lower frequency of C/T genotype in late-onset male psoriasis vulgaris (P = 0.029) as well as of T allele in female early-onset psoriasis vulgaris (P = 0.049) were ascertained. Conclusions On condition that all other genetic or environmental factors remain stable, the existence and possible interaction between GJB2 rs3751385 C and T alleles in male psoriatic patients may be considered as protective gene component against late-onset psoriasis appearance, while presence of the T allele in female might block the histogenetic mechanisms of early-onset psoriasis lesions.

Skin Barrier Dysregulation in Psoriasis

“…Connexin 26 (CX26), one of the smallest connexins, is almost entirely absent in healthy epidermis but is one of the most highly upregulated proteins in psoriatic plaques [ 47 ]. GJB2 , which encodes CX26, is the 98th most upregulated gene detected, and its overexpression is used as a marker of genetic predisposition in psoriasis [ 48 , 49 ]. The inhibition of CX26 expression diminishes inflammatory pathways and may be therapeutically useful in psoriasis [ 50 ].…”

Connexins and the Epithelial Tissue Barrier: A Focus on Connexin 26

“…More recently, publication of the psoriatic transcriptome permitted in depth RNAseq analysis [ 107 ] and many of the upregulated genes are related with cell-to-cell adhesion complexes. GJB2 , encoding CX26 was the 98th most up-regulated gene detected and its over expression is used as a marker of genetic predisposition in psoriasis [ 108 , 109 ]. A variety of other transcriptomic studies confirm this overall increase in CX26 expression in psoriatic tissue yet no changes in CX43 gene expression are reported [ 110 , 111 ].…”

Interactions of host defense and hyper-keratinization in psoriasis

“…These proinflammatory mediators stimulate the keratinocytes leading to hyper-keratinization ultimately leading to overexpression of keratinocyte differentiation markers (SPRR1B/2A/2D/2E, GJB2/6) (46–48), regulators (CRABP2) (49) and proteases (KLK7/13) (50). Interestingly, PI3 was also secreted by keratinocytes to hinder the neutrophil chemotaxis in skin.…”