Genetic and functional studies of the LMF1 gene in Thai patients with severe hypertriglyceridemia

Abstract

Severe hypertriglyceridemia (HTG) due to chylomicronemia is associated with acute pancreatitis and is related to genetic disturbances in several proteins involved in triglyceride (TG) metabolism. Lipase maturation factor 1 (LMF1) is a protein essential for the maturation of lipoprotein lipase (LPL). In this study, we examined the genetic spectrum of the LMF1 gene among subjects with severe HTG and investigated the functional significance of 6 genetic variants in vitro. All 11 exons of the LMF1 gene were sequenced in 101 Thai subjects with severe HTG. For an in vitro study, we performed site-directed mutagenesis, transient expression in cld cells, and measured LPL protein and LPL activity. We identified 2 common variants [p.(Gly36Asp) and p.(Pro562Arg)] and 12 rare variants [p.(Thr143Met), p.(Asn249Ser), p.(Ala287Val), p.(Met346Val), p.(Thr395Ile), p.(Gly410Arg), p.(Asp433Asn), p.(Asp491Asn), p.(Asn501Tyr), p.(Ala504Val), p.(Arg523His), and p.(Leu563Arg)] in 29 patients. In vitro study of the p.(Gly36Asp), p.(Asn249Ser), p.(Ala287Val), p.(Asn501Tyr), p.(Pro562Arg) and p.(Leu563Arg) variants, however, revealed that both LPL mass and LPL activity in each of the transfected cells were not significantly different from those in the wild type LMF1 transfected cells, suggesting that these variants might not play a significant role in severe HTG phenotype in our subjects.

Keywords

• LMF1
• Variants
• Lipoprotein lipase
• Triglyceride
• Chylomicron
• Chylomicronemia