[Genetic markers and psoriasis in three ethnic populations of Dagestan]
Analysis of clinical material obtained from the individuals (49 psoriasis patients and 357 individuals without this disease) representing three ethnic populations of Dagestan (Avars, Dargins, and Kumyks) was performed. Polymorphism of the blood group loci AB0, Rhesus (RH), Kell, P, and Lewis, as well as of the protein-encoding loci for haptoglobin (HP), group-specific component (GC), and the enzymes, including glycosylase (GL01), esterase D (ESD), 6-phosphate dehydrogenase (6PDG), and acid phosphatase (ACP), was studied. It was demonstrated that in the pooled sample of Avars and Kumyks the Lewis system phenotype Le(a-b-) and the RH homozygotes (ee/ee) were statistically significantly more frequent among the psoriasis patients (P = 0.0488 and P = 0.0166, respectively), than among healthy controls of the same ethnic groups. It was suggested that for the pooled sample of Avars and Kumyks, homozygosity for the recessive RH allele (ee/ee) in combination with the Le(a-b-) phenotype, representing homozygosity for recessive allele le, was the risk factor for the development of psoriasis.
- [Show abstract] [Hide abstract] ABSTRACT: Nuclear factor kappa-beta (NF-κB) is a critical transcription factor modulating the expression of many genes involved in the pathogenesis of psoriasis. SUMO4 is a negative regulator of NF-κB in the cell-signaling pathway. Two functional polymorphisms of the NFKB1 and SUMO4 genes have been found to be associated with the risks of some autoimmune-related diseases, but no published study has investigated the role of these polymorphisms in the etiology of psoriasis in the Chinese population. In this hospital-based, case-control study of 519 Chinese psoriasis vulgaris patients and 541 matched controls, we genotyped the NFKB1-94 ins/delATTG and the SUMO4 rs237025 A>G polymorphisms and assessed their respective associations with psoriasis vulgaris risk. We found that the genotype distribution of NFKB1-94 ins/delATTG polymorphism was statistically different between psoriasis patients and controls (P = 0.031). But the difference was not still statistically significant after correction for multiple comparisons. The frequency of wild WW genotype in psoriasis patients was statistically higher than that in controls (35.8 vs. 29.0%, respectively, P = 0.021). The W allele frequency in cases was also significantly higher than that in controls (59.7 vs. 54.1%, P = 0.008). Compared with the DD genotype, a significantly increased psoriasis risk was associated with the NFKB1 WW genotype (adjusted OR = 1.57, 95% CI = 1.10-2.24). In addition, the WW genotype frequency was also statistically higher in the psoriatic subgroups of onset age ≤40, PASI >20, male patients and sporadic patients than that in controls. But, no associations of the SUMO4 rs237025 A>G polymorphism with the susceptibility of psoriasis were detected. In conclusion, we found a marginal association between the NFKB1-94 ins/delATTG WW genotype and the increased psoriasis vulgaris risk and the association was more evident in the subgroups of onset age ≤40, PASI >20, male patients and sporadic patients in Chinese.
- [Show abstract] [Hide abstract] ABSTRACT: Receptor for advanced glycation end-products is implicated in a development of chronic inflammatory response. Aim of this paper is to provide a review on commercial and experimental medicines that can interfere with RAGE and signaling through RAGE. We searched three bibliographical databases (PubMed, Web of Science and MEDLINE) for the publications from 2005 to March 2012 and identified 5 major groups of agents that can interfere with RAGE biological effects. In the first part of this paper, we discuss AGE crosslink breakers. These chemicals destroy advanced glycation end products (AGEs) that are crosslinked to the extracellular matrix proteins and can interact with RAGE as ligands. Then, we describe two non-conventional agents SAGEs and KIOM-79 that abolish certain biological effects of RAGE and have a strong anti-inflammatory potential. In the third part, we evaluate the inhibitors of the signaling cascades that underlie RAGE. Particularly, we discuss two groups of kinase inhibitors tyrphostins and the inhibitors of JAK kinases. Considering RAGE as a potential master regulator of processes that are crucial for the pathogenesis of psoriasis, we propose that these medicins may help in controlling the disease by abolishing the chronic inflammation in skin lesions.