Dataset Information

Functional Polymorphisms in IRAKs Are Related to Hepatocellular Carcinoma Risk in Chinese Population.

ABSTRACT: 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.

SUBMITTER: Wang H

PROVIDER: S-EPMC6077667 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Functional Polymorphisms in <i>IRAKs</i> Are Related to Hepatocellular Carcinoma Risk in Chinese Population.

Wang Hui H Song Ci C Qi Qi Q Huang Tongtong T Wang Lijuan L Chen Jianguo J Zhu Jian J Hu Zhibin Z Dai Juncheng J

BioMed research international 20180709

<h4>Background</h4>Interleukin 1 receptor associated kinases <i>(IRAKs)</i> play a central role in TLR signaling pathway. Scarce literature has investigated the association of potential functional genetic variants of <i>IRAKs</i> with Hepatitis B Virus- (HBV-) related hepatocellular carcinoma (HCC).<h4>Methods</h4>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 ...[more]

PMID: 30112356

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Project description:BackgroundPolymorphisms of genes encoding components of the vitamin D pathway including vitamin D receptor (VDR) and vitamin D binding protein (DBP) have been widely investigated because of the complex role played by vitamin D in cancer tumorogenesis. In this study, we investigated the association between VDR and DBP gene polymorphisms and HBV-related HCC risk in a Chinese population.MethodsStudy subjects were divided into three groups: 184 HBV patients with HCC, 296 HBV patients without HCC, and 180 healthy controls. The VDR rs2228570, and rs3782905 and the DBP rs7041 polymorphisms were genotyped using PCR-RFLP and the VDR rs11568820 polymorphism was genotyped by PCR-SSP, respectively. DNA sequencing was performed to validate the genotype results.ResultsWe found that there were significant differences in the genotype and allele frequencies of the VDR rs2228570 and DBP rs7041 polymorphisms between HBV patients with HCC and healthy controls. The rs2228570 T allele was associated with a significant increased HBV-related HCC risk as compared with the C allele. The rs2228570 TT and TT/TC genotypes were correlated with a significant increased HBV-related HCC risk when compared with the wild-type CC homozygote. Similarly, the rs7041 G allele was associated with a significant increased HBV-related HCC risk as compared with the T allele. The rs7041 GG and GG/TG genotypes were correlated with a significant increased HBV-related HCC risk when compared with the wild-type TT homozygote. However, we did not observe any significant effect of VDR rs11568820, and rs3782905 polymorphisms on HBV-related HCC risk in this population. In haplotype analysis, we also did not find any significant differences in haplotype frequencies of the VDR gene between HBV patients with HCC and the healthy controls.ConclusionsWe conclude that the VDR rs2228570 and DBP rs7041 polymorphisms may contribute to increased susceptibility to HBV-related HCC in the Chinese population. Due to the marginal significance, further large and well-designed studies in diverse ethnic populations are needed to confirm our results.

Dataset Information

Functional Polymorphisms in IRAKs Are Related to Hepatocellular Carcinoma Risk in Chinese Population.

Publications

Functional Polymorphisms in <i>IRAKs</i> Are Related to Hepatocellular Carcinoma Risk in Chinese Population.

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