MBOAT7-TMC4 rs641738 Is Not Associated With the Risk of Hepatocellular Carcinoma or Persistent Hepatitis B Infection

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.

MBOAT7 in liver and extrahepatic diseases

“…A recent study on a Thai cohort composed of HCC patients with different etiological backgrounds did not reveal any association between the MBOAT7 rs641738 polymorphism and the development of HCC 71 . The same MBOAT7 rs641738 variant did not have a statistically significant association with advanced liver stiffness 72,73 or hepatitis C virus‐induced liver cirrhosis, probably due to the etiological heterogeneity of the liver cirrhosis cohort and to a small number of patients within the subgroup analysis 68,74 …”

“…This new variant might influence MBOAT7 mRNA expression and, therefore, its hepatic protein expression, suggesting that the rs641738 C>T may not be the causal variant linking MBOAT7 to SLD 66 . On the other hand, several studies showed that neither heterozygous nor homozygous carriage of the MBOAT7 rs641738 variant confer any increased risk of HCC development or HBV infection persistency or clearance 67–69 …”

Association of MBOAT7 rs641738 polymorphism with hepatocellular carcinoma susceptibility: A systematic review and meta-analysis

“…Furthermore, two studies focused on HCC arising from NAFLD[ 12 ] or metabolic dysfunction-associated fatty liver disease[ 13 ], while another two[ 9 , 14 ] investigated a mixed cohort of NAFLD, viral, and alcohol-related HCC. One study[ 15 ] encompassed HCC occurring in the context of compensated cirrhosis (HCV or alcohol), and one[ 16 ] did not specify the particular characteristics of the included patient cohort. The genetic analysis techniques employed were diverse, with the TaqMan genotyping method being utilized in most studies ( n = 5), with one study employing the MassARRAY[ 16 ] and two[ 12 , 13 ] employing United Kingdom Biobank Axiom array methodologies.…”

Personalized medicine and nutrition in hepatology for preventing chronic liver disease in Mexico

“…However, the rs641738 T allele was not associated neither with HCC risk nor HBV infection in Chinese patients. ( 122 ).…”