Introduction
Sepsis, a syndrome caused by a dysregulated immune response to infection, is a life-threatening worldwide health issue[1]. Globally, there were an estimated 48.9 million cases of sepsis and 11.0 million potential sepsis-related deaths in 2017[2]. According to the age, sepsis incidence peaked in early childhood who were younger than 5 years, representing 41.5% (estimated 20.3 million) of overall cases of sepsis in 2017[2]. At present, despite advances in the diagnosis and treatment of sepsis, it remains a clinical challenge for clinicians and researchers due to the fact that sepsis is still the main cause of mortality worldwide[2, 3].
Over the past decade, the development of genomics has substantially provided us with a better understanding of the biological pathway involved in various human diseases[4]. Emerging studies have demonstrated that polymorphisms of the genetic components encoding inflammation-associated mediators were markedly associated with the development of human sepsis[5-9]. Recently, non-coding RNAs, including microRNAs, long non-coding RNAs(lncRNAs) and circular RNAs, were also proven to mediate the pathogenesis of sepsis and could serve as biomarkers for septic diagnosis[10-12]. Currently, most studies predominantly focus on functions of microRNAs in sepsis, little is known about the relationship between lncRNAs and sepsis.
LncRNA is a type of RNA with more than 200 nucleotides in length[10, 13]. Although lacking of protein-coding capacity, lncRNAs have been found to be related to so many pathological processes of human diseases[10]. LincRNA-NR_024015 , also known as testis development related 1(TDRG1 ), is a newly identified tumor-associated lncRNA. Studies have shown that lncRNA TDRG1could serve as a proto-oncogene in multiple tumor types[14-17]. Chen and colleagues revealed that lncRNA TDRG1 might promote endometrial carcinoma cell proliferation and invasion by targeting vascular endothelial growth factor (VEGF)[16]. It has long been documented that VEGF serves as a critical regulator of vascular permeability and inflammation[18-20]. Furthermore, growing evidences have indicated that the level of plasma VEGF was markedly associated with the development of human sepsis[21-25]. Based on these findings, we considered that TDRG1 might have critical effects on the pathogenesis of sepsis by interacting with VEGF. Although significant correlations were recently found between the polymorphism of lncRNA TDRG1 rs8506 and cancer susceptibility[26, 27], its association with sepsis susceptibility and clinical outcomes has not been addressed yet.
In terms of the potential immunopathological roles of lncRNATDRG1 in sepsis, the present study aimed to investigate the association between the lncRNA TDRG1 rs8506 polymorphism and sepsis susceptibility in the current hospital-based case–control study with 474 cases and 678 healthy controls in a southern Chinese child population.