A novel lipoprotein lipase gene missense mutation in Chinese patients with severe hypertriglyceridemia and pancreatitis

Abstract

BackgroundAlterations or mutations in the lipoprotein lipase (LPL) gene contribute to severe hypertriglyceridemia (HTG). This study reported on two patients in a Chinese family with LPL gene mutations and severe HTG and acute pancreatitis.MethodsTwo patients with other five family members were included in this study for DNA-sequences of hyperlipidemia-related genes (such as LPL, APOC2, APOA5, LMF1, and GPIHBP1) and 43 healthy individuals and 70 HTG subjects were included for the screening of LPL gene mutations.ResultsBoth patients were found to have a compound heterozygote for a novel LPL gene mutation (L279V) and a known mutation (A98T). Furthermore, one HTG subject out of 70 was found to carry this novel LPL L279V mutation.ConclusionsThe data from this study showed that compound heterozygote mutations of A98T and L279V inactivate lipoprotein lipase enzymatic activity and contribute to severe HTG and acute pancreatitis in two Chinese patients. Further study will investigate how these LPL gene mutations genetically inactivate the LPL enzyme.

A common variant association study in ethnic Saudi Arabs reveals novel susceptibility loci for hypertriglyceridemia

“…The encoded APOA1 protein is a cofactor for the lecithin cholesterol acyltransferase, which plays an important role in the cholesterol reverse transport by promoting its efflux from tissue to the liver for excretion. Notably, another gene at the same locus, APOA5, has been previously associated with hTG, and both genes have been concomitantly implicated in the disease (13,(36)(37)(38)(39)(40). Hence, the strong link of this variant to hTG observed in this study unequivocally points to a central role for the APOA1 gene in this disorder.…”

A common variant association study reveals novel susceptibility loci for low HDL‐cholesterol levels in ethnic Arabs

“…Several common variant association studies (CVASs) formerly called genome-wide association studies (GWASs), resequencing and targeted approaches have revealed a wealth of information on the genetic basis for dyslipidemia, and several predisposing genes identified thus far have been implicated in hypercholesterolemia (4-6), hypertriglyceridemia (7)(8)(9)(10)(11)(12)(13) or low HDL-cholesterol levels (14)(15)(16)(17)(18). Despite the volume of these data on dyslipidemia-related genes, only a fraction of the heritability of the disease traits has been explained thus far, and the predisposing gene variants, particularly for LHDLC, are far from being completely unraveled (19).…”

Association of the HindIII Lipoprotein Lipase Gene Polymorphism with the Development of the Non-Biliary Acute Pancreatitis: a Pilot Study

“…More than 100 mutations in the LPL gene significantly impairing enzyme activity are described [4], many of these are intensively studied in the context of their relationship with hereditary lipid metabolism disorders and acute pancreatitis developing against this background [6,7,9]. In particular, in Chinese population the association between the L279V, A98T [7], L252V, and С264T mutations in LPL gene with HTG development and severity of acute pancreatitis was revealed. The most commonly studied polymorphisms of LPL gene affecting blood triglyceride content are S477X (rs328), PvuII (rs285), and HindIII (rs320) [9].…”

“…It is known that lipoprotein lipase enzyme (LPL) plays the key role in the regulation of lipid metabolism, especially in hydrolysis of triglycerides [12]. Although LPL gene is polymorphic, but we found only few studies on the relationship of these polymorphisms with the risk of disease development [6,7,9].…”