Key result
Six LMF1 genetic variants identified in Thai patients with severe hypertriglyceridemia showed no significant difference in LPL mass or activity compared to wild type in vitro.
Why the study?
Severe hypertriglyceridemia is linked to acute pancreatitis and genetic disturbances in triglyceride metabolism, but the genetic spectrum and functional significance of LMF1 variants were unclear.
Observational (n=101)
Genetic variants in the LMF1 gene identified in Thai patients with severe hypertriglyceridemia did not significantly alter LPL mass or activity in vitro, suggesting they may not play a major role in the severe HTG phenotype.
LMF1 variants show minimal functional impact on severe hypertriglyceridemia; leaves open other genetic or environmental drivers for further study.
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.
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Plengpanich et al. (2020) conducted an observational in Severe hypertriglyceridemia (n=101). LMF1 gene variants vs. Wild type LMF1 was evaluated on LPL mass and LPL activity. Six LMF1 genetic variants identified in Thai patients with severe hypertriglyceridemia showed no significant difference in LPL mass or activity compared to wild type in vitro.
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