Research Article
Association between polymorphisms in TLR4 gene targeted by microRNA-140 and cervical precancerous lesion in south Chinese women: a case control study
Published: November 15, 2017
Genet. Mol. Res. 16(4): gmr16039831
DOI: https://doi.org/10.4238/gmr16039831
Cite this Article:
C. Huang, Z. Li, X. Zhong, Y. Wang, X. Ye, L. Jing, S. Huang, Q. Yin, Z. Miao, Z. Zhou, Y. Liu, X. Ye, Y. Han, M. Ou, D. Xiao, C. Guo, C. Zeng, G. Yang, C. Jing, X. Wei (2017). Association between polymorphisms in TLR4 gene targeted by microRNA-140 and cervical precancerous lesion in south Chinese women: a case control study. Genet. Mol. Res. 16(4): gmr16039831. https://doi.org/10.4238/gmr16039831
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Abstract
Toll-like receptor 4 (TLR4), one of the key immune
system effectors, plays a main role in immune recognition of cervical
cancer. Micro-RNAs are involved in regulation of multiple important
genes in the progression of cervical cancer. A case-control study of
592 people was conducted from Yun’an County, Yunfu City,
Guangdong Province, China. Cervical fall off epithelia were
collected to detect human papilloma virus (HPV), followed by Thin
Prep cytology test (TCT). Moreover, extraction of DNA from
peripheral blood were performed for genotyping from the 296
patients and another 296 age-matched healthy control subjects.
Logistic regression was used to determine the risk genotypes for
susceptibility to cervical precancerous lesion, and multifactor
dimensionality reduction (MDR) was further employed to
preliminarily investigate the gene-environment interaction on risk of
cervical precancerous lesion. Gene expression of miRNA-140 from
serum was done by real-time PCR. We investigated whether target
sites of TLR4 gene polytheisms (rs11536896 T>C, rs7873784 G>C)
of miR-140 were associated with cervical precancerous lesion risk.
The alleles C>A of SNP rs11536896 were significantly different in
ASCUS in comparison of case group and control group with HPV
infection. The presence of the allele C was associated with a higher
risk of developing ASCUS lesion in HPV negative women (OR:
1.75, 95%CI:1.20-2.54, p = 0.003). There was statistically significant
difference between the expression of miRNA 140 and the
susceptibility to cervical precancerous lesion, in which there is
down-regulation of the miRNA-140 in case group (T=6.73，
P=0.007). Gene-environment interaction analysis by MDR software
revealed an association among rs7873784 and hrHPV infection and
more types of infected HPV (p < 0.0001, OR: 25.48; 95%Cl: 5.20-
124.84). Collectively, these results suggested that rs11536896 and
rs787378 from TLR4 gene were associated with risks of cervical
precancerous lesion. Thus, this miRNA-140 and SNPs（
rs11536896rs787378） of TLR4 gene could be considered as a
potential molecular mechanism and biomarker for detecting and
diagnosing cervical cancer in early time.
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