No variant was significantly associated with impulse control disorders or related behaviors after correction for multiple testing, although the 2 top variants were close to significant (OPRM1 rs179991, OR, 0.49; 95%CI, 0.32-0.76; P = 0.0013; Bonferroni adjusted P = 0.065; DAT1 40-base pair variable number tandem repeat, OR, 1.82; 95%CI, 1.24-2.68; P = 0.0021; Bonferroni adjusted P = 0.105).
In the future, it may be possible to use a precision medicine approach to decrease the incidence of ICDs in PD by avoiding DA use in patients determined to be at highest risk based on their clinical and neurobiological (e.g., motor presentation, behavioral measures of medication response, genetics, dopamine transporter neuroimaging) profile.
These results indicate that epidermal keratinocyte IL-6Rα function modulates epidermal hyperplasia, immune cell infiltration into skin and cytokine expression during ICD and suggests that the previously reported protective effect of IL-6 during ICD might be mediated primarily by keratinocyte derived IL-6Rα.
These results show that IL-6 modulates the IL-22/IL-22R<i>α</i> axis in the skin and suggest that this occurrence may be associated with the increased epidermal hyperplasia and exacerbated inflammatory response observed in IL-6R<i>α</i><sup>Δker</sup> mice during ICD.
The most important development has been the discovery that loss-of-function mutations in the gene encoding the epidermal protein filaggrin increase the risk for ICD and for nickel sensitization and nickel ACD, emphasizing the importance of the skin barrier in the pathophysiology of CD.
The prevalence of worsened score at study end was higher in CRT-D than ICD patients (26.4% vs. 18.2%; P = 0.014), as was mortality (7.4% vs. 4.1%; P = 0.069).
These results indicate that epidermal keratinocyte IL-6Rα function modulates epidermal hyperplasia, immune cell infiltration into skin and cytokine expression during ICD and suggests that the previously reported protective effect of IL-6 during ICD might be mediated primarily by keratinocyte derived IL-6Rα.
These results highlight a previously unknown role of IL-6Rα function in myeloid cells in modulating the inflammatory response and myeloid population dynamics during ICD.