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Lipoprotein lipase and apolipoprotein E polymorphisms : relationship to hypertriglyceridemia associated with pregnancy McGladdery, Sandra Helen

Abstract

Normal pregnancy is associated with a mild increase in plasma total cholesterol (TC) and a 3 to 4-fold increase in plasma triglycerides (TG). Plasma TG concentration is determined by the balance between the rate of production of TG-rich lipoproteins and the rate of removal of these lipoproteins from the circulation by lipolytic enzymes such as lipoprotein lipase (LPL) and hepatic lipase (HL) and its subsequent uptake by the liver through apo E receptor. Complete deficiency of LPL is manifested as chylomicronemia, a rare autosomal co-dominant disorder. While heterozygous individuals rarely present with chylomicronemia they may have a milder form of hypertriglyceridemia. Variations in the apo E gene have also been associated with increases in plasma TG in addition to changes in plasma TC, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). Because of the overproduction of TG-rich VLDL, normal pregnancy challenges the lipolytic capacity of LPL and the ability to clear remnants via the apo E receptor. Cases of chylomicronemia and pancreatitis occurring during pregnancy have been reported in previously healthy women. During the course of pregnancy, LPL and apo E polymorphisms may cause TG levels to increase. It is hypothesized that pregnant women carrying some of these polymorphisms will develop more severe hypertriglyceridemia during the course of pregnancy. The objective of this thesis is to investigate the impact of three known LPL polymorphisms (Asp9Asn, Asn291 Ser, Ser447X) and the apo E genotype (4/4, 4/3, 3/3, 3/2, 2/4, 2/2) on lipid levels during pregnancy. Two hundred and fifty healthy women in the 3rd trimester of pregnancy were recruited. Fasting plasma TG, TC, HDL-C, LDL-C, insulin, glucose and fractional esterification rate of HDL (FER[sub HDL]) were measured. Analysis of the LPL and apo E genes' polymorphisms were performed, in addition to sequencing of the LPL gene in 5 women with the highest TG levels. The frequencies of the LPL (D9N, 0.9%; N291S, 4.6%; S447X, 18%) and the apo E (E2, 7.6%; E3, 81.4 %, E4, 11.0%) polymorphisms were similar to previously published results in non-pregnant women. Carriers of S447X had significantly lower TG levels (p=0.003), and carriers of the N291S had significantly lower HDL-C levels (p

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