J Clin Lab Anal. 2018;32:e22292. wileyonlinelibrary.com/journal/jcla
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© 2017 Wiley Periodicals, Inc.
Correlation between TLR2, TLR3, TLR4, and TLR9
polymorphisms and susceptibility to and prognosis of
severe hepatitis among the newborns
Xiao Qiu | Yubin Dong | Yaqin Cao | Yingmei Luo
Department of Neonatal Intensive Care
Unit, The Central Hospital of Zhoukou City,
Zhoukou, Henan Province, China
Xiao Qiu, Department of Neonatal Intensive
Care Unit, The Central Hospital of Zhoukou
City, Zhoukou City, Henan Province, China.
Background: This study was aimed to explore how toll- like receptor 2 (TLR2), TLR3,
TLR4 and TLR9 influenced the risk and prognosis of severe hepatitis among the Chinese
Methods: Altogether 135 newborns diagnosed with severe hepatitis and 140 healthy
newborns were included in this study. Totally 12 single nucleotide polymorphisms
(SNPs) within TLR2, TLR3, TLR4, and TLR9 were chosen and genotyped by polymerase
chain reaction- restriction fragment length polymorphism (PCR- RFLP). Odds ratios
(ORs) and 95% confidence intervals (CIs) were calculated using the logistic regression.
The univariate and multivariate analyses were used to analyze independent factors for
prognosis of severe hepatitis among the Chinese newborns.
Results: The SNPs within TLR2 [ie, rs1898830 (A>G) and rs3804100 (T>C)], TLR3 [ie,
rs1879026 (G>T)], TLR4 [ie, rs2149356 (T>G)], and TLR9 [ie, rs187084 (T>C),
rs352139 (A>G), and rs352140 (C>T)] were significantly associated with modified risk
of neonatal severe hepatitis (all P<.05). Furthermore, rs1898830, rs1879026,
rs187084 and rs352139 were also demonstrated to modulate the prognosis [ie, as-
partate aminotransferase (AST)/alanine transaminase (ALT)>1.5] of newborns with
severe hepatitis (all P<.05). Interestingly, the haplotype A- C- G- G- C- A- T were associ-
ated with higher susceptibility to neonatal severe hepatitis, and the newborns carry-
ing haplotype A- C- G- G- C- A- T appeared to be correlated with more favorable
prognosis (all P<.05).
Conclusions: Certain SNPs and haplotypes within TLR2, TLR3, TLR4, and TLR9 can be
considered as the potentially treatment targets for neonatal severe hepatitis.
neonatal severe hepatitis, prognosis, SNP, susceptibility, TLR2, TLR3, TLR4, TLR9
1 | INTRODUCTION
Perinatal infection was the main cause of neonatal liver damage, es-
pecially the fetal infection caused by TORCH syndrome (ie, toxoplas-
mosis, listerellosis, rubella virus, cytomegalovirus and herpes simplex
virus). Human cytomegalovirus (HCMV) was widely located in the na-
ture, and the positive rates of HCMV antibodies were, respectively,
around 95% among pregnant women and 83.2% among children in
Infection of HCMV could induce proportional changes of the
subsets of T lymphocyte cells within infants, and determination of the
cell subsets was of significance to judging the severity of active HCMV
infection and guiding early- stage treatment.
Besides, liver not merely
regulated the digestion, metabolism and endocrine systems, but also
participated in the immune adjustment. For instance, there existed di-
verse immunoregulation- related cells within liver (eg, Kupffer cell, den-
dritic cell and lymphocyte), and the cells were responsible for antigen