Polymorphisms in miRNA Genes Targeting the AMPK Signaling Pathway are Associated with Cervical Cancer Susceptibility in a Han Chinese Population

Abstract

Xueya Chen,1,* Zhiling Yan,2,* Weipeng Liu,1 Lili Guo,1 Jinmei Xu,2 Li Shi,3 Yufeng Yao1 1Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming, People’s Republic of China; 2Department of Gynaecologic Oncology, The No. 3 Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 3Department of Immunogenetics, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li Shi, Department of Immunogenetics, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming, Yunnan, 650118, People’s Republic of China, Email [email protected] Yufeng Yao, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming, Yunnan, 650118, People’s Republic of China, Email [email protected]; [email protected]: Cervical cancer (CC) poses a significant threat to women’s health worldwide, and multiple signaling pathways have been confirmed to be involved in its development. The AMPK signaling pathway plays a central role in maintaining energy homeostasis, and its dysregulation is closely associated with the occurrence of CC. Changes in microRNA (miRNA) expression levels might be related to the AMPK signaling pathway. Single nucleotide polymorphisms (SNPs) can affect the function of miRNA and result in the development of CC. To investigate the association between the SNPs of AMPK pathway-associated miRNAs and CC in a Han Chinese population, we selected eight miRNA genes located in the AMPK pathway and analyzed nine SNP loci within these genes to explore whether they are associated with genetic susceptibility to cervical intraepithelial neoplasia (CIN) and CC.Methods: A total of 2,220 subjects were included in this study, including 928 healthy controls, 421 CIN patients, and 871 CC patients. Nine candidate SNPs (rs895819 in miR-27a, rs10061133 in miR-449b, rs41291179 in miR-216a, rs76481776 in miR-182, rs10406069 in miR-5196, rs12803915 and rs550894 in miR-612, rs66683138 in miR-3622b, and rs2620381 in miR-627) were genotyped using the TaqMan method.Results: The results showed significant differences in the allele distribution of rs41291179 and rs12803915 between the control group and the CIN group, as well as between the control group and the CC group (all P values < 0.005). The A allele of rs41291179 and the G allele of rs12803915 were associated with decreased risk of CIN (OR = 0.05, 95% CI: 0.01– 0.39; OR = 0.61, 95% CI: 0.49– 0.76) and CC (OR = 0.08, 95% CI: 0.01– 0.66; OR = 0.71, 95% CI: 0.59– 0.86), respectively.Conclusion: Our results suggest that polymorphisms in miRNA genes of the AMPK signaling pathway are associated with the development of CC.Keywords: genotyping, SNP, gene enrichment, genetic susceptibility

Keywords

• genotyping
• snp
• gene enrichment
• genetic susceptibility