We assessed the familial correlation of PRO-C3 concentration, the shared gene effects between PRO-C3 concentration and liver steatosis and fibrosis, and the association between PRO-C3 concentration and genetic variants in the patatin-like phospholipase domain-containing 3 (PNPLA3), transmembrane 6 superfamily member 2 (TM6SF2), membrane-bound O-acyltransferase domain-containing (MBOAT), and glucokinase regulator (CGKR) genes.
Metabolic effects of LYPLAL1 rs12137855-C were similar, but statistically less robust, to the effects of GCKR rs1260326-T. TM6SF2rs58542926-T displayed opposite metabolic effects when compared with the fatty liver associations.
Furthermore, the low-frequency E167K variant of TM6SF2 and rare mutations in APOB, which impair very low-density lipoproteins secretion, predispose to progressive fatty liver.
The T allele was associated with alterations in serum lipids and hepatic steatosis in all diseases and with reduced hepatic TM6SF2 and microsomal triglyceride transfer protein expression.
Neither variant TM6SF2 nor MBOAT7 increased hepatic steatosis (all P>.05); however, the MBOAT7 polymorphism was associated with increased triglyceride, total cholesterol, low density lipoprotein, and serum glucose levels (all P<.05).
Reduction of Caloric Intake Might Override the Prosteatotic Effects of the PNPLA3 p.I148M and TM6SF2p.E167K Variants in Patients with Fatty Liver: Ultrasound-Based Prospective Study.
The Glu167Lys (E167K) transmembrane 6 superfamily member 2 (TM6SF2) variant has been associated with liver steatosis, high alanine transaminase (ALT) levels and reduced plasma levels of liver-derived triglyceride-rich lipoproteins.