Genski polimorfizmi citokina high mobility group box-1 kod kritično obolelih pacijenata sa sepsom i traumom

Abstract

Uvod/cilj: High-mobility group box 1 (HMGB1) prptein ima različite ćelijske funkcije, sa značajnpm ulogom u arhitekturi hromatina i regulaciji transkripcije. Takođe, HMGB1 ima različite efekte na imunski sistem i deluje kap prp-inflamatprni citpkin, pojačavajući urođeni i stečeni imunski odgovor, te učestvuje u patpgenezi različitih bolesti, od sepse do autoimunskih bolesti i kancera. Ova studija je pročavala pojedinačne nukleptidne polimprfizme (single nucleotide polymorphisms- SNP) na pozicijama rs2249825 [C/T], rs4540927 [G/A], rs19299606 [C/T], rs17074615 [A/C], rs1412125 [T/C], rs1060348 [C/T], rs1045411 [G/A], rs3742305 [G/C] u genu za high-mobility group box 1 (HMGB1) protein u grupi kritično obolelih pacijenata sa sepspm i traumom. Metode: klinička opservacipna analitička studija preseka. Studija je sprovedena na 119 kritično obolelih pacijenata sa sepspm i traumpm. Genotipizacija za citpkin sa HMGB1 za 8 polimprfizma (SNPs) je vršena kpristeći Taq-Man SNP Genotyping Assays, Applied Biosystems. Statistička obrada podataka je vršena preko SPSS 20.0 software (IBM Corp., Armonk, NY, USA). Udruženost između kategorija je vršena preko hi-kvadrat testa ( chi-square test). Količnik šanse -Odds ratios (OR) sa intervalom poverenja od 95% (95% confidence intervals- CI) je izračunat preko multiple logističke regresije (multiple logistic regression analysis) u cilju procene relativnog rizika u zavisnosti od mortaliteta, godina, pola i bakterijskog uzročnika infecije korišćene kao kovarijante u multiploj logističkpj regresiji. P vrednost < .05 je smatrana značajnom. Rezultati: U analizi polimorfizma (SNP), 5 njih su pokazali klinički značajnost u genu za highmobility group box 1 (HMGB1) protein na pozicijama rs2249825 [C/T], rs1412125 [T/C], rs1060348 [C/T], rs1045411 [G/A] i rs3742305 [G/C] kod kritično obolelih pacijenata sa sepspm i traumom. Tri polimorfizma u genu za high-mobility group box 1 (HMGB1) protein na pozicijama rs2249825[C/T], rs1045411 [G/A] and rs3742305 [G/C] su udruženi sa uzročnikpm bakterijskih infekcija, prema nalazu iz hempkulture. Jedan polimorfizam na poziciji rs1060348 [C/T] je udružen sa osnovnom bolešću (peritpnitis, pankreatitis) koja je dovela do sepse. Zaključci Ova studija je proučavala pojedinačne nukleptidne polimprfizme (single nucleotide polymorphisms- SNP) u genu za high-mobility group box 1 (HMGB1) citpkin u grupi kritično obolelih pacijenata sa sepspm i traumpm. Nije upočena povezanost između pojedinačhih polimorfima i ishoda bolesti. Neki pd proučavanih polimprfizma su pokazali udruženost sa bakterijskim uzročnikpm infekcije (prema nalazu hempkultura) i osnovne bolesti (peritonitis, pankreatitis) koja dovodi do sepse.

Background/Aim: High-mobility group box 1 (HMGB1) protein has diverse cellular functions, with important role in chromatin architecture and transcriptional regulation. HMGB1 has diverse effects on immunity acting as a pro-inflammatory cytokine, enhancing both innate and adaptive immune response that contribute to the pathogenesis of various disorders, from sepsis and autoimmunity to cancer. This study examined the single nucleotide polymorphisms (SNP) at position rs2249825 [C/T], rs4540927 [G/A], rs19299606 [C/T], rs17074615 [A/C], rs1412125 [T/C], rs1060348 [C/T], rs1045411 [G/A], rs3742305 [G/C] in high-mobility group box 1 (HMGB1) gene in critically ill patients with sepsis and trauma. Methods: Clinical prospective observational analytical cross-sectional study. The study was conducted on 119 critically ill patients with sepsis and trauma. HMGB1 genotypes for 8 SNPs were assessed using Taq-Man SNP Genotyping Assays, Applied Biosystems. Statistical analysis was performed with the SPSS 20.0 software (IBM Corp., Armonk, NY, USA). The association between categorical variables was estimated by the chi-square test. Odds ratios (OR) with 95% confidence intervals (CI) were calculated by multiple logistic regression analysis to estimate relative risk of mortality, age, sex ratio and type of bacteria were used as covariances of multiple logistic regression. P values < .05 were considered significant. Results: In analyzing the polymorphisms, five single nucleotide polymorphisms (SNP) in high-mobility group box 1 (HMGB1) gene have clinical significance at position rs2249825 [C/T], rs1412125 [T/C], rs1060348 [C/T], rs1045411 [G/A] and rs3742305 [G/C] in critically ill patients with sepsis and trauma. No association between SNP and outcome in our study. Three single nucleotide polymorphisms (SNP) in high-mobility group box 1 (HMGB1) gene at position rs2249825[C/T], rs1045411 [G/A] and rs3742305 [G/C] associated with type of bacteria according to the findings of blood culture. One single nucleotide polymorphisms (SNP) at position rs1060348 [C/T] is associated with the basic disease (peritonitis, pancreatitis) which led to sepsis. Conclusion: This study examined the single nucleotide polymorphisms (SNP) in high-mobility group box 1 (HMGB1) gene in critically ill patients with sepsis and trauma. No association between SNP and outcome. Some of the studied SNP showed association with type of bacteria (according to the findings of blood culture) and the basic disease (peritonitis, pancreatitis) which led to sepsis.