“…Meanwhile, hypomethylated DMRs in PP were particularly associated with the polyol metabolic process, which is one of the major biochemical pathways involved in the development of diabetic macroangiopathy and peripheral neuropathy (Katakami, 2018). It has been shown that there is a significant correlation between psoriasis/diabetes and the polyol metabolic process (Mamizadeh et al, 2019), so we consider that these hypomethylated DMRs in PP may provide a clue to explain why psoriasis is related to diabetes.…”
N 6-methyladenosine (m 6 A) methylation, as the most prevalent internal RNA modification, has been revealed to play critical roles in various biological functions. In this study, we performed m 6 A transcriptome-wide profiling in three kinds of skin tissue: involved psoriatic skin (PP), uninvolved psoriatic skin (PN), and healthy control skin samples (NN). The findings revealed that transcripts of PP contained the fewest m 6 A peaks and lowest m 6 A peak density. The greatest differences of m 6 A methylation were observed in the PP vs. NN and PP vs. PN comparisons. Intriguingly, in these comparisons, hypermethylated m 6 A was mainly enriched within the CDSs and 3 UTRs, while hypomethylated m 6 A was not only enriched within CDSs and 3 UTRs, but also within 5 UTRs. GO and KEGG pathway analyses indicated that hypermethylated transcripts in PP were particularly associated with response-associated terms, cytokine production, and olfactory transduction. Meanwhile, hypomethylated transcripts in PP were mainly associated with development-related processes and the Wnt signaling pathway. In addition, we discovered that 19.3-48.4% of the differentially expressed transcripts in psoriasis vulgaris were modified by m 6 A, and that transcripts with lower expression were more preferentially modified by m 6 A. Moreover, upregulation of gene expression was often accompanied by upregulation of m 6 A methylation, suggesting a regulatory role of m 6 A in psoriasis vulgaris gene expression.
“…Meanwhile, hypomethylated DMRs in PP were particularly associated with the polyol metabolic process, which is one of the major biochemical pathways involved in the development of diabetic macroangiopathy and peripheral neuropathy (Katakami, 2018). It has been shown that there is a significant correlation between psoriasis/diabetes and the polyol metabolic process (Mamizadeh et al, 2019), so we consider that these hypomethylated DMRs in PP may provide a clue to explain why psoriasis is related to diabetes.…”
N 6-methyladenosine (m 6 A) methylation, as the most prevalent internal RNA modification, has been revealed to play critical roles in various biological functions. In this study, we performed m 6 A transcriptome-wide profiling in three kinds of skin tissue: involved psoriatic skin (PP), uninvolved psoriatic skin (PN), and healthy control skin samples (NN). The findings revealed that transcripts of PP contained the fewest m 6 A peaks and lowest m 6 A peak density. The greatest differences of m 6 A methylation were observed in the PP vs. NN and PP vs. PN comparisons. Intriguingly, in these comparisons, hypermethylated m 6 A was mainly enriched within the CDSs and 3 UTRs, while hypomethylated m 6 A was not only enriched within CDSs and 3 UTRs, but also within 5 UTRs. GO and KEGG pathway analyses indicated that hypermethylated transcripts in PP were particularly associated with response-associated terms, cytokine production, and olfactory transduction. Meanwhile, hypomethylated transcripts in PP were mainly associated with development-related processes and the Wnt signaling pathway. In addition, we discovered that 19.3-48.4% of the differentially expressed transcripts in psoriasis vulgaris were modified by m 6 A, and that transcripts with lower expression were more preferentially modified by m 6 A. Moreover, upregulation of gene expression was often accompanied by upregulation of m 6 A methylation, suggesting a regulatory role of m 6 A in psoriasis vulgaris gene expression.
“…The overlapping epidemiology of these conditions highlights this connection and the significant associations that have been found between DM and all these other phenotypes. [7][8][9][10][11][12][13][14][15] However, we propose these connections go beyond mere epidemiologic links due to overlapping pathophysiology. In fact, these conditions occur together in enough frequency and have common overlapping pathophysiologic drivers that we have created a conceptual framework called "The Diabetes Syndrome".…”
mentioning
confidence: 90%
“…(ASCVD), and nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). [4][5][6][7][8][9][10][11][12][13][14][15] In clinical practice we often encounter these common diseases, frequently within one individual patient and they are treated as independent conditions. However, we believe their epidemiologic associations is, in part, due to the same underlying pathophysiologies driving β-cell damage and diabetic complications.…”
The four basic pathophysiologic mechanisms which damage the β-cell within diabetes (ie, genetic and epigenetic changes, inflammation, an abnormal environment, and insulin resistance [IR]) also contribute to cell and tissue damage and elevate the risk of developing all typical diabetes-related complications. Genetic susceptibility to damage from abnormal external and internal environmental factors has been described including inflammation and IR. All these mechanisms can promote epigenetic changes, and in total, these pathophysiologic mechanisms interact and react with each other to cause damage to cells and tissues ultimately leading to disease. Importantly, these pathophysiologic mechanisms also serve to link other common conditions including cancer, dementia, psoriasis, atherosclerotic cardiovascular disease (ASCVD), nonalcoholic fatty liver disease (NAFLD), and nonalcoholic steatohepatitis (NASH). The "Diabetes Syndrome", an overarching group of interrelated conditions linked by these overlapping mechanisms, can be viewed as a conceptual framework that can facilitate understanding of the interrelationships of superficially disparate conditions. Recognizing the association of the conditions within the Diabetes Syndrome due to common pathophysiologies has the potential to provide both benefit to the patient (eg, prevention, early detection, precision medicine) and to the advancement of medicine (eg, driving education, research, and dynamic decision-based medical practice).
“…Psoriasis is associated with several metabolic risk factors, including obesity, type 2 diabetes mellitus, hypertension and dyslipidaemia . These metabolic abnormalities are also more common in patients with greater psoriasis severity than in those with milder disease.…”
Summary
Psoriasis is a chronic inflammatory disease that is commonly encountered in primary care and is associated with significant morbidity that extends beyond the skin manifestations.
Psoriasis is associated with an elevated risk of psoriatic arthritis, cardiovascular disease, obesity, insulin resistance, mental health disorders, certain types of malignancy, inflammatory bowel disease and other immune‐related disorders, and hepatic and renal disease.
Enhanced recognition of these comorbidities may lead to earlier diagnosis and potentially better overall health outcomes.
Psoriatic nail involvement, severe skin disease and obesity are associated with a greater risk of psoriatic arthritis. Individuals with psoriasis should be routinely screened for psoriatic arthritis to allow for early intervention to improve long term prognosis.
Life expectancy is reduced in people with psoriasis due to a variety of causes, with cardiovascular disease and malignancy being the most common aetiologies.
Psoriasis affects several factors that contribute to worsened quality of life and increased risk of depression and anxiety. Effective therapies are now available that have been shown to concurrently improve skin disease, quality of life and psychiatric symptoms.
As the concordance between psychosocial impact and objective disease severity does not always correlate, it is essential to tailor management strategies specifically to the needs of each individual.
Cigarette smoking and excess alcohol consumption are among the most important modifiable risk factors that increase the likelihood of psoriasis development and severity of skin disease. This provides a compelling rationale for smoking cessation and limiting alcohol intake in people with psoriasis beyond their traditional harmful health consequences.
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