LNC-ZNF33B-2:1 gene rs579501 polymorphism is associated with organ dysfunction and death risk in pediatric sepsis

Zhaoliang Lu; Hongyan Yu; Yufen Xu; Kaining Chen; Yueling Lin; Kun Lin; Yishuai Wang; Kaixiong Xu; Lanyan Fu; Weizhan Li; Huazhong Zhou; Bing Wei; Lei Pi; Di Che; Xiaoqiong Gu

doi:10.3389/fgene.2022.947317

LNC-ZNF33B-2:1 gene rs579501 polymorphism is associated with organ dysfunction and death risk in pediatric sepsis

Front Genet. 2022 Sep 8:13:947317. doi: 10.3389/fgene.2022.947317. eCollection 2022.

Authors

Zhaoliang Lu^{1

2}, Hongyan Yu², Yufen Xu², Kaining Chen², Yueling Lin², Kun Lin², Yishuai Wang², Kaixiong Xu², Lanyan Fu², Weizhan Li³, Huazhong Zhou², Bing Wei², Lei Pi², Di Che², Xiaoqiong Gu^{2

4}

Affiliations

¹ The School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, Guangdong, China.
² Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Department of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
³ Medical Oncology, Panyu Central Hospital, Guangzhou, Guangdong, China.
⁴ Department of Blood Transfusion and Clinical Lab, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.

Abstract

Background: Sepsis is a severe systemic reaction disease induced by bacteria and virus invading the bloodstream and subsequently causing multiple systemic organ dysfunctions. For example, the kidney may stop producing urine, or the lungs may stop taking in oxygen. Recent studies have shown that long non-coding RNAs (lncRNAs) are related to the dysfunction of organs in sepsis. This study aims to screen and validate the sepsis-associated lncRNAs and their functional single nucleotide polymorphisms (SNPs). Result: Unconditional multiple logistic regression based on the recessive model (adjusted odds ratio = 2.026, 95% CI = 1.156-3.551, p = 0.0136) showed that patients with the CC genotype of rs579501 had increased risk of sepsis. Stratification analysis by age and gender indicated that patients with the rs579501 CC genotype had higher risk of sepsis among children aged <12 months (adjusted odds ratio = 2.638, 95% CI = 1.167-5.960, p = 0.0197) and in male patients (adjusted odds ratio = 2.232, 95% CI = 1.127-4.421, p = 0.0213). We also found a significant relationship between rs579501 and severe sepsis risk (CC versus AA/AC: adjusted odds ratio = 2.466, 95% CI = 1.346-4.517, p = 0.0035). Stratification analysis for prognosis and number of organ dysfunctions demonstrated that the rs579501 CC genotype increased non-survivors' risk (adjusted odds ratio = 2.827, 95% CI = 1.159-6.898, p = 0.0224) and one to two organs with dysfunction risk (adjusted odds ratio = 2.253, 95% CI = 1.011-5.926, p = 0.0472). Conclusion: Our findings showed that the lnc-ZNF33B-2:1 rs579501 CC genotype increases the susceptibility to sepsis. From the medical perspective, the lnc-ZNF33B-2:1 rs579501 CC genotype could be serving as a biochemical marker for sepsis.

Keywords: long non-coding RNA (lncRNA); rs579501; sepsis; single nucleotide polymorphism; susceptibility.