Polymorphism of thePEMTgene and susceptibility to nonalcoholic fatty liver disease (NAFLD)

Abstract

Phosphatidylethanolamine N-methyltransferase (PEMT) catalyzes phosphatidylcholine synthesis. PEMT knockout mice have fatty livers, and it is possible that, in humans, nonalcoholic fatty liver disease (NAFLD) might be associated with PEMT gene polymorphisms. DNA samples from 59 humans without fatty liver and from 28 humans with NAFLD were genotyped for a single nucleotide polymorphism in exon 8 of PEMT which leads to a V175M substitution. V175M is a loss of function mutation, as determined by transiently transfecting McArdle-RH7777 cells with constructs of wildtype PEMT open reading frame or the V175M mutant. Met/Met at residue 175 (loss of function SNP) occurred in 67.9% of the NAFLD subjects and in only 40.7% of control subjects (p< 0.03). For the first time we report that a polymorphism of the human PEMT gene (V175M) is associated with diminished activity and may confer susceptibility to NAFLD.

Serum choline plasmalogens, particularly those with oleic acid in sn-2, are associated with proatherogenic state

“…Supplemental Material can be found at: ( 26 ). Interestingly, a polymorphism of the human PEMT gene is associated with diminished activity and may confer susceptibility to nonalcoholic fatty liver disease (NAFLD) ( 27,28 ). NAFLD shares common clinical manifestations with MetS, such as abdominal obesity, T2D, dyslipidemia, and insulin resistance ( 29 ).…”

Hepatic Phosphatidylethanolamine N-Methyltransferase, Unexpected Roles in Animal Biochemistry and Physiology

“…In apparent contrast, no association was found between the V175M polymorphism and steatosis in the Dallas Heart Study (62). The patients examined in the Dallas Heart Study included multiple races (63), whereas in the study by Song et al (60), most subjects were Caucasian. When only Caucasian subjects were compared, there was a similar relationship between the V175M polymorphism and liver disease (63).…”

“…A polymorphism in the human PEMT gene is associated with nonalcoholic fatty liver disease (60). Controls and patients with liver disease were evaluated for a Val-to-Met substitution at residue 175 of the PEMT human protein.…”

Genetic determinants of hepatic steatosis in man

“…A small study of reported that the frequency of the PEMT variant V175M was higher in 28 biopsy-confi rmed NAFLD patients (0.81) compared with control subjects with normal hepatic triglyceride content (0.61) ( 193 ). In addition, in vitro transfection experiments in McArdle-RH7777 cells showed that V175M had diminished activity compared with wild-type PEMT ( 193 ).…”