TY - JOUR A2 - Li, Ming D. AU - Wang, Hui AU - Song, Ci AU - Qi, Qi AU - Huang, Tongtong AU - Wang, Lijuan AU - Chen, Jianguo AU - Zhu, Jian AU - Hu, Zhibin AU - Dai, Juncheng PY - 2018 DA - 2018/07/09 TI - Functional Polymorphisms in IRAKs Are Related to Hepatocellular Carcinoma Risk in Chinese Population SP - 1252849 VL - 2018 AB - Background. Interleukin 1 receptor associated kinases (IRAKs) play a central role in TLR signaling pathway. Scarce literature has investigated the association of potential functional genetic variants of IRAKs with Hepatitis B Virus- (HBV-) related hepatocellular carcinoma (HCC). Methods. A case-control study with 1,538 HBV-positive HCC patients and 1,465 chronic HBV carriers was conducted to evaluate the effects of common missense variants of IRAK family members on HCC. Proliferation assays and real-time polymerase chain reactions were carried out to evaluate the functions. Multivariable adjusted logistic regression was adopted to estimate effect size and identify risk factors. Results. Association analysis indicated that rs4251545 A allele of IRAK4 (p.Ala428Thr) was positively associated with HBV-related HCC risk (OR = 1.30, 95% CI: 1.09–1.54, P=0.003). Functional annotation indicated that rs4251545 reduced its own expression in liver (P=0.031). Further molecular functional analysis detected that rs4251545 increased the proliferation rate of L02 cells (P<0.05). Meanwhile, rs4251545 reduced mRNA expressions of IL-6, IL-8, CXCL-1, and CXCL-2 in L02 cells (P<0.01). Conclusion. rs4251545 of IRAK4 (p.Ala428Thr) modified the susceptibility to HBV-related HCC via increased proliferation rate and reduced production of inflammatory cytokines and chemokines. Further well-designed experiments are warranted to validate our findings. SN - 2314-6133 UR - https://doi.org/10.1155/2018/1252849 DO - 10.1155/2018/1252849 JF - BioMed Research International PB - Hindawi KW - ER -