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Association between polymorphisms in TLR4 gene targeted by microRNA-140 and cervical precancerous lesion in south Chinese women: a case control study

Author(s): Chuican Huang , Zhongyi Li , Xingming Zhong, Yao Wang, Xingguang Ye, Lipeng Jing, Shiqi Huang, Qian Yin , Zhulin Miao, Zixing Zhou, Yang Liu, Xiaohong Ye, Yajing Han, Meiling Ou, Di Xiao , Congcong Guo, Chengli Zeng, Guang Yang, Chunxia Jing, Xiangcai Wei

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