Association of MBOAT7-TMC4 rs641738 with the risk of hepatocellular carcinoma and persistent infection of hepatitis B virus: a case-control study and meta-analysis

Abstract

Background: Recent studies reported that a hot genetic variant, rs641738 within the membrane bound O-acyltransferase domain containing 7(MBOAT7) and transmembrane channel-like 4 (TMC4) , was associated with several liver diseases. However, results are still conflicting. We conducted this study to explore the role of MBOAT7-TMC4 rs641738 in the risk of hepatocellular carcinoma (HCC) and persistent hepatitis B virus (HBV) infection. Methods: We first performed a case-control study by including 779 HCC cases and 1412 cancer-free controls. Controls are consisted of 678 HBV persistent carriers and 734 spontaneously recovered subjects. Rs641738 was genotyped by MassARRAY platform. Results were analyzed by multivariate logistic regression analysis under five genetic models. Second, we conducted a systematic review and meta-analysis to further explore the role of this variant in HCC risk. Results: 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 recessive model ( P = 0.044). Further meta-analysis including 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. Besides, we identified that this variant also had no influence on persistent HBV infection. Conclusion: Our 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.