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.