Abstract
ObjectiveA hot genetic variant, rs641738 within the membrane-bound O-acyltransferase domain containing 7(MBOAT7) and transmembrane channel-like 4 (TMC4), was recently reported to be associated with several liver diseases. However, the results remain controversial. Therefore, this study aimed to explore the role of MBOAT7-TMC4 rs641738 in the risk of hepatocellular carcinoma (HCC) and persistent hepatitis B virus (HBV) infection.MethodsWe first conducted a case-control study that included 779 HCC cases and 1412 cancer-free controls. Controls consisted of 678 persistent HBV carriers and 734 spontaneously recovered subjects. The gene variant rs641738 was genotyped using the MassARRAY platform. The results were analyzed in five genetic models using multivariate logistic regression analyses. Next, we performed a systematic review and meta-analysis to further explore the role of this variant in HCC risk.ResultsThe results suggested no association between MBOAT7-TMC4 rs641738 and HCC risk in most genetic models (all P > 0.05). Although a marginally significant association was observed in TT vs. CC (P = 0.037) and the recessive models (P = 0.044). The meta-analysis of 2135 HCC cases and 4388 controls supported that this variant was not related to HCC risk, even in the TT vs. CC and recessive models. We also determined that this variant did not influence persistent HBV infection.ConclusionOur work highlights that MBOAT7-TMC4 rs641738 is not associated with the risk of HCC or persistent HBV infection. This study provides some clues to identify the “truth” of potential disease-related genetic factors in the post-genome era.
Highlights
Hepatocellular carcinoma (HCC) is a common rapidly progressing cancer, with high mortality worldwide, especially in China [1]
In 2015, a genome-wide association studies (GWASs) study reported that a genetic variant near the membrane-bound O-acyltransferase domain containing 7 (MBOAT7) gene, rs641738, C>T, increased the risk of alcoholrelated cirrhosis [5]
Helsley et al first reported that genetic deletion of Tmc4 in mice may not lead to hepatic steatosis, but the loss of function of its neighboring gene Mboat7 could result in liver disease progression in mice [7]
Summary
Hepatocellular carcinoma (HCC) is a common rapidly progressing cancer, with high mortality worldwide, especially in China [1]. As the fourth most common cancer in China, 466,100 new cases were estimated in 2015 [2] Environmental factors such as hepatitis B virus (HBV) infection have been confirmed to be crucial in the pathogenesis of HCC [3]. In 2015, a GWAS study reported that a genetic variant near the membrane-bound O-acyltransferase domain containing 7 (MBOAT7) gene, rs641738, C>T, increased the risk of alcoholrelated cirrhosis [5]. Helsley et al first reported that genetic deletion of Tmc in mice may not lead to hepatic steatosis, but the loss of function of its neighboring gene Mboat could result in liver disease progression in mice [7]. In 2016, Thabet et al demonstrated that MBOAT7-TMC4 rs641738 could be a risk factor for hepatic inflammation and liver fibrosis [8]. Subsequent studies further investigated the association between this variant and HCC risk, but led to conflicting conclusions [9,10,11]
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