The MBOAT7 variant rs641738 alters hepatic phosphatidylinositols and increases severity of non-alcoholic fatty liver disease in humans

The membrane‐bound O‐acyltransferase domain‐containing 7 variant rs641738 increases inflammation and fibrosis in chronic hepatitis B

“…Finally, neither PNPLA3 rs738409 nor TM6SF2 rs58542926 were associated with inflammation and fibrosis, though they were associated with steatosis. Collectively, in the context of other published reports, these results indicate that MBOAT7 is a risk locus for inflammation (and consequently fibrosis) across multiple liver diseases.…”

“…AA also induces apoptosis, a potent trigger for liver inflammation and fibrosis, and amplifies the inflammatory response in macrophages and other immune cells . The rs641738 (T) allele that is associated with an increased risk of hepatic inflammation is coupled to decreased hepatic MBOAT7 mRNA and protein expression, as well as reduced arachidonoyl‐phosphatidylinositol/total phosphatidylinositol ratios, indicating attenuated enzymatic activity . Furthermore, we have shown strong MBOAT7 expression in virtually all common immune cell subsets that infiltrate the liver during viral hepatitis .…”

Additive effects of PNPLA3 and TM6SF2 on the histological severity of non‐alcoholic fatty liver disease

“…Our data did not reveal any association between MBOAT7‐TMC4 rs641738 and the histologic severity of NAFLD. MBOAT7 is also known as lysophosphatidylinositol acyltransferase 1 ( LPIAT1 ), and rs641738 in MBOAT7‐TMC4 has been reported to be associated with NAFLD; however, it was confirmed only in the European population. Our data were based on the Asian population, and further studies are needed to confirm the association in other ethnic populations with NAFLD.…”

“…Established risk alleles for NAFLD were selected for genotyping. Specifically, the PNPLA3 rs738409 C>G (I148M), TM6SF2 rs58542926 C>T (E167K), and MBOAT7 ‐TMC4 C>T rs641738 single‐nucleotide polymorphisms were genotyped in the entire cohort by TaqMan 5′‐nuclease assays (Life Technologies, Carlsbad, CA, USA) according to the manufacturer's instructions. Hardy–Weinberg equilibrium was confirmed using the chi‐squared test.…”

“…Recently, in addition to metabolic risk factors, several genetic variants have been reported to influence the risk of NAFLD. The patatin‐like phospholipase domain‐containing 3 ( PNPLA3 ), transmembrane 6 superfamily member 2 ( TM6SF2 ), and membrane bound O‐acyltransferase domain containing 7‐transmembrane channel‐like 4 ( MBOAT7‐TMC4 ) genes are known to increase the risk of NAFLD and its histological severity. Previous studies have reported conflicting results regarding an interaction between the genotype and metabolic phenotype in the risk of hepatic steatosis …”