The rs13388259 Intergenic Polymorphism in the Genomic Context of the BCYRN1 Gene Is Associated with Parkinson’s Disease in the Hungarian Population

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by bradykinesia, resting tremor, and muscle rigidity. To date, approximately 50 genes have been implicated in PD pathogenesis, including both Mendelian genes with rare mutations and low-penetrance genes with common polymorphisms. Previous studies of low-penetrance genes focused on protein-coding genes, and less attention was given to long noncoding RNAs (lncRNAs). In this study, we aimed to investigate the susceptibility roles of lncRNA gene polymorphisms in the development of PD. Therefore, polymorphisms (n = 15) of the PINK1-AS, UCHL1-AS, BCYRN1, SOX2-OT, ANRIL and HAR1A lncRNAs genes were genotyped in Hungarian PD patients (n = 160) and age- and sex-matched controls (n = 167). The rare allele of the rs13388259 intergenic polymorphism, located downstream of the BCYRN1 gene, was significantly more frequent among PD patients than control individuals (OR = 2.31; p = 0.0015). In silico prediction suggested that this polymorphism is located in a noncoding region close to the binding site of the transcription factor HNF4A, which is a central regulatory hub gene that has been shown to be upregulated in the peripheral blood of PD patients. The rs13388259 polymorphism may interfere with the binding affinity of transcription factor HNF4A, potentially resulting in abnormal expression of target genes, such as BCYRN1

Re-investigating the Basement Membrane Zone of Psoriatic Epidermal Lesions: Is Laminin-511 a New Player in Psoriasis Pathogenesis?

Psoriasis is a complex chronic inflammatory skin disease characterized by epidermal thickening on the basis of increased keratinocyte proliferation and insufficient apoptosis. Laminins are important components of the basement membrane (BM) and impact on epidermal keratinocyte growth/apoptosis. Although several laminins are involved in the pathogenesis of psoriasis, it is still controversial about the expression patterns of laminin isoforms and which laminins are important in the development of psoriasis. Because laminin-511 and -332 are key BM components in human skin, and laminin-511 stimulates human hair follicle growth, we asked whether the BM zone in psoriasis shows any laminin-related abnormalities. This showed that the BM expression of laminin-511 and -332 was significantly increased within the skin lesion of psoriasis. Immunofluorescence microscopy revealed that laminin-511, -332, and collagen type IV proteins were also significantly increased in psoriasis-like skin lesions of Imiquimod-treated mice. Transmission electron microscopy showed a few gaps of lamina densa, and its thickness was significantly increased. Finally, laminin-511 treatment significantly stimulated the proliferation and inhibited apoptosis of HaCaT cells, while laminin-α5 chain gene knockdown decreased proliferation and induced apoptosis. These phenomenological observations raise the question of whether laminin-511-controlled keratinocyte growth/death may be a previously overlooked player in the pathogenesis of psoriatic epidermal lesions