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.
Highlights
Hypertriglyceridemia-induced pancreatitis (HTP) is a rare yet serious complication of pregnancy, usually developing in the late gestation
There were no mutations found in apolipoprotein C2 (APOC2), apolipoprotein A5 (APOA5) or lipase maturation factor 1 (LMF1) genes
Homozygous p.G185C mutation is strongly associated with extreme HTG. [27, 28]
Summary
Hypertriglyceridemia-induced pancreatitis (HTP) is a rare yet serious complication of pregnancy, usually developing in the late gestation. It is a potentially life threatening condition, both for the mother and the fetus.[1] In normal pregnancy, there is a 2- to 4-fold increase in serum triglyceride (TG) levels due to increased hepatic synthesis of very-low-density lipoproteins (VLDL) in response to elevated estrogen levels and reduced lipoprotein lipase (LPL). Genetic Variants Cause Severe Hypertriglyceridemia during Pregnancy activity.[2] this moderate physiological hypertriglyceridemia (HTG) is seldom associated with any adverse clinical consequences. Severe HTG with a fasting plasma TG level of more than 1000 mg/dl (11.3 mmol/l), is known to be an independent risk factor for acute pancreatitis (AP).[3]
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