Regulation of CIRP by genetic factors of SP1 related to cold sensitivity

Abstract

Cold-inducible RNA-binding-protein (CIRP) is a cold shock protein that plays a protective role in genotoxic stress response. CIRP modulates inflammation in human diseases, inhibits cell proliferation, and protects cells from genotoxic damage during cellular stress. The mild cold responsive element and specificity protein 1 (SP1) play a role in Cirp expression at low temperatures. Although previous studies have provided insights into the immune functions of SP1 or CIRP, the mechanisms by which CIRP and SP1 me diate inflammatory responses remain largely unknown. Therefore, in the current study, we examined whether Cirp expression is affected by genetic factors related to temperature sensitivity as well as under low temperature. We performed a genome-wide association study on cold sensitivity in 2,000 participants. Fifty-six genome-wide significant trait-locus pairs were identified (p<1×10-5, false discovery rate < 0.05). Among these variants, rs1117050 and rs11170510 had a strong linkage disequilibrium (r2 > 0.8) relationship and expression quantitative trait locus-associated signals with the nearest Sp1 gene. We confirmed that the minor alleles of rs11170510 and rs58123204 were associated with increased Sp1 expression. Additionally, Sp1 overexpression led to CIRP translocation from the nucleus to the cytoplasm. CIRP protein levels increased in serum samples that had minor alleles of rs11170510 and rs58123204. Levels of various pro-inflammatory cytokines were also significantly increased in human peripheral blood mononuclear cells with minor alleles of rs11170510 and rs58123204. These results suggest that genetic factors related to cold sensitivity regulate CIRP expression and function and provide valuable insights into prediction of potential diseases through analysis of inherent genetic factors in humans.

Partial sleep restriction-induced changes in stress, quality of life, and lipid metabolism in relation to cold hypersensitivity: A before-and-after intervention study

“…[ 23 , 24 ] Furthermore, genetic factors related to cold sensitivity were founded in the latest study, they regulated expression and function of cold-inducible RNA-binding-protein in inflammatory response. [ 25 ] Although we did observe that individuals close to CH status had small negative stress responses to inadequate sleep, there were no clearly significant differences in inflammatory markers between the CH and non-CH groups. Further studies will be needed considering CH-related epigenetic processes in sleep disturbances.…”

“…[23,24] Furthermore, genetic factors related to cold sensitivity were founded in the latest study, they regulated expression and function of cold-inducible RNA-binding-protein in inflammatory response. [25] Although we did observe that individuals Table 2 Correlation between CH score and changes in each variable during sleep restriction and follow-up. close to CH status had small negative stress responses to inadequate sleep, there were no clearly significant differences in inflammatory markers between the CH and non-CH groups.…”

Genome-wide Analysis Identified SEMA4D, Novel Candidate Gene for Temperature Sensitivity in Patients With Non-Small Cell Lung Cancer

“… 15 Recently, a genome-wide association study (GWAS) of a population-based cohort suggested that the CIRP gene is associated with CP. 16 However, reports on genetic analysis with temperature sensitivity are still limited. Moreover, a GWAS in diverse cohorts is necessary for the discovery of candidate genes that lead to the disclosure of the genetic implications of temperature sensitivity.…”