Abstract
BackgroundGreat progress has been made in the understanding of inflammatory processes in psoriasis. However, clarifying the role of genetic variability in processes regulating inflammation, including post-transcriptional regulation by microRNA (miRNA), remains a challenge.ObjectivesWe therefore investigated single nucleotide polymorphisms (SNPs) with a predicted change in the miRNA/mRNA interaction of genes involved in the psoriasis inflammatory processes.MethodsStudied SNPs rs2910164 C/G–miR-146a, rs4597342 T/C–ITGAM, rs1368439 G/T–IL12B, rs1468488 C/T–IL17RA were selected using a bioinformatics analysis of psoriasis inflammation-associated genes. These SNPs were then genotyped using a large cohort of women with psoriasis (n = 241) and healthy controls (n = 516).ResultsNo significant association with psoriasis was observed for rs2910164, rs1368439, and rs1468488 genotypes. However, the major allele T of rs4597342 –ITGAM was associated with approximately 28% higher risk for psoriasis in comparison to the patients with the C allele (OR = 1.28, 95% CI 1.01–1.61, p = 0.037). In case of genotypes, the effect of the T allele indicates the dominant model of disease penetrance as the CT and TT genotypes increase the chance of psoriasis up to 42% in comparison to CC homozygotes of rs4597342 (OR = 1.42, 95% CI = 1.05–1.94, p = 0.025).ConclusionSNP rs4597342 in 3'UTR of ITGAM influencing miR-21 binding may be considered a risk factor for psoriasis development. Upregulated miR-21 in psoriasis is likely to inhibit CD11b production in the case of the rs4597342 T allele which may lead to Mac-1 dysfunction, resulting in an aberrant function of innate immune cells and leading to the production of cytokines involved in psoriasis pathogenesis.
Highlights
IntroductionGreat progress has been made in the understanding of inflammatory processes involved in psoriasis pathogenesis in recent years
The major allele T of rs4597342 –ITGAM was associated with approximately 28% higher risk for psoriasis in comparison to the patients with the C allele (OR = 1.28, 95% CI 1.01–1.61, p = 0.037)
The effect of the T allele indicates the dominant model of disease penetrance as the CT and TT genotypes increase the chance of psoriasis up to 42% in comparison to CC homozygotes of rs4597342 (OR = 1.42, 95% CI = 1.05–1.94, p = 0.025)
Summary
Great progress has been made in the understanding of inflammatory processes involved in psoriasis pathogenesis in recent years. Inflammatory processes in psoriasis are influenced by a range of genetic, epigenetic and environmental factors One such epigenetic factor are microRNAs (miRNA), small ~22 nucleotides long molecules of non-coding RNA, regulating gene expression at the post-transcriptional level by sequence-specific binding to the 3’UTR of target genes [2]. This fine-tuned tool regulates multiple target genes and significantly impacts a wide range of cellular processes including the development and behavior of inflammatory cell subsets, thereby affecting inflammatory response [3]. Clarifying the role of genetic variability in processes regulating inflammation, including post-transcriptional regulation by microRNA (miRNA), remains a challenge
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have