Polymorphism of the glucocorticoid receptor gene (NR3C1) in chronic illnesses: a protocol of a scoping review

Abstract

AbstractDuring process like local or systemic homeostatic disturbances due to infection, tissue injury, trauma or surgery, neoplastic growth or immunological disorders, the host responds with a defensive reaction, the acute phase response, which encompasses alterations in immune, metabolic, neuroendocrine functions. Beyond the triggering stimulus, innate immune cells, quickly manage to deal with such a threat and secrete proinflammatory cytokines like Tumour Necrosis Factor alpha (TNF-α), Interleukin 1 beta (IL-1β), and Interleukin 6 (IL-6). Beyond their immunological effects, these cytokines also activate the stress system within the central nervous system leading to the activation of the hypothalamic-pituitary-adrenal axis as an effectors arm. As such, the immune response mounted against pathogens is paralleled by a significantly altered hormonal response. In relation to the immunomodulatory influences of adrenal steroids, glucocorticoids (GCs) suppress the immune system at several levels, avoiding the possible adverse effects of an excessive immune response and helping to terminate it once the noxious stimulus was eliminated. Under some circumstances, particularly at the beginning of the immune response, GCs can also exert pro-inflammatory effects. But at high concentrations, GCs generally suppress immune and inflammatory responses arising during activation of innate and adaptive immune responses. As in many physiological processes, individual sensitivity to GCs is variable being determined by genetic and acquired factors. This kind of versatility of GCs effects, that also extends to immune cells, may be due to a series of mechanisms, including a familiar resistance linked to inactivating mutations of GR or SNP -Single Nucleotide Polymorphism-functions affecting transcription. In this context, we will conduct a Scoping Review (ScR) of the literature about SNPs in the glucocorticoid receptor gene (NR3C1).The general aim of this ScR is to examine the extent and nature of available evidence on chronic illnesses associated with SNPs in the glucocorticoid receptor gene. The scoping review will assess evidence from all observational study designs. We will conduct a search in MEDLINE and LILACS. No language restriction will be applied. We will also search The Cochrane Library, and Epistemonikos to identify systematic reviews as an additional mechanism to identify primary studies. These searches will aim to identify all articles related to SNPs in the GR gene and will not be restricted to those evaluating specific conditions. These searches will be supplemented by scanning references of relevant retrieved articles to identify any additional relevant studies. References will be screen by titles and abstracts, remaining potentially relevant articles will be screen as full texts. Two reviewers will independently screen all identified records for relevance. Conflicts between reviewers will be solved by consensus or by the lead systematic reviewer in consultation with the content experts, if required. We will create a diagram to show the number of studies in each population condition. One reviewer will chart the data using pre-tested data-charting forms. This data charting will be double-checked for accuracy by a second reviewer. We will resolve any disagreements about data extraction by referring to the study report and through discussion. Once data is charted for all included studies, we will tabulate the data for each new condition identified. Findings from the scoping reviews will be reported according to the newly developed, PRISMA for Scoping Reviews (PRISMA-ScR). When interpreting the review findings, we will make sure that the limitations of different study designs are carefully considered, though no quality assessment will be performed.