title: Genetic Variants Associated with Gestational Hypertriglyceridemia and Pancreatitis.
abstract: Severe hypertriglyceridemia is a well-known cause of pancreatitis. Usually, there is a moderate increase in plasma triglyceride level during pregnancy. Additionally, certain pre-existing genetic traits may render a pregnant woman susceptible to development of severe hypertriglyceridemia and pancreatitis, especially in the third trimester. To elucidate the underlying mechanism of gestational hypertriglyceridemic pancreatitis, we undertook DNA mutation analysis of the lipoprotein lipase (LPL), apolipoprotein C2 (APOC2), apolipoprotein A5 (APOA5), lipase maturation factor 1 (LMF1), and glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) genes in five unrelated pregnant Chinese women with severe hypertriglyceridemia and pancreatitis. DNA sequencing showed that three out of five patients had the same homozygous variation, p.G185C, in APOA5 gene. One patient had a compound heterozygous mutation, p.A98T and p.L279V, in LPL gene. Another patient had a compound heterozygous mutation, p.A98T & p.C14F in LPL and GPIHBP1 gene, respectively. No mutations were seen in APOC2 or LMF1 genes. All patients were diagnosed with partial LPL deficiency in non-pregnant state. As revealed in our study, genetic variants appear to play an important role in the development of severe gestational hypertriglyceridemia, and, p.G185C mutation in APOA5 gene appears to be the most common variant implicated in the Chinese population. Antenatal screening for mutations in susceptible women, combined with subsequent interventions may be invaluable in the prevention of potentially life threatening gestational hypertriglyceridemia-induced pancreatitis.
authors.affiliation: The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
authors.forename: Sai-Li
authors.initials: SL
authors.lastname: Xie
authors.affiliation: The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
authors.forename: Tan-Zhou
authors.initials: TZ
authors.lastname: Chen
authors.affiliation: Ren-Ji Study, Wenzhou Medical University, Wenzhou, China.
authors.forename: Xie-Lin
authors.initials: XL
authors.lastname: Huang
authors.affiliation: The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Chen
authors.affiliation: The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Jin
authors.affiliation: The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
authors.forename: Zhi-Ming
authors.initials: ZM
authors.lastname: Huang
authors.affiliation: The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
authors.forename: Meng-Tao
authors.initials: MT
authors.lastname: Zhou
mesh_terms: D000328:Adult; D000072040:Apolipoprotein A-V; D053304:Apolipoprotein C-II / Q000235:genetics; D001054:Apolipoproteins A / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D006801:Humans; D015228:Hypertriglyceridemia / Q000150:complications*; D008071:Lipoprotein Lipase / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics; D010195:Pancreatitis / Q000209:etiology* / Q000235:genetics*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000209:etiology* / Q000235:genetics*; D018110:Receptors, Lipoprotein / Q000235:genetics; D055815:Young Adult
chemical_list: C437704:APOA5 protein, human; D000072040:Apolipoprotein A-V; D053304:Apolipoprotein C-II; D001054:Apolipoproteins A; C523701:GPIHBP1 protein, human; C546366:LMF1 protein, human; D008565:Membrane Proteins; D018110:Receptors, Lipoprotein; C548261:LPL protein, human; D008071:Lipoprotein Lipase