Gene-environment interaction in the conversion of a mild-to-severe phenotype in a patient homozygous for a Ser172-->Cys mutation in the lipoprotein lipase gene.

Abstract

Normal pregnancy is associated with a two-to threefold increase in plasma triglyceride levels, particularly in the third trimester, due both to the overproduction of VLDLs and to the possible suppression. of lipoprotein lipase (LPL) activity. Numerous mutations in the human LPL gene causing complete LPL deficiency have been described, but naturally occurring mutations that result in defective LPL with partial activity have not yet been reported. Here we describe a 30-yr-old woman who was first diagnosed with LPL deficiency during pregnancy after she developed pancreatitis. Her plasma triglyceride levels remained mildly elevated at approximately 300 mg/dl (3.4 mmol/liter) after the first pregnancy but rose significantly after she became pregnant again (1800 to 2000 mg/dl) (20.2 to 22.5 mmol/liter). DNA sequence analysis of the LPL gene showed that the patient is homozygous for a Ser '72-Cys missense mutation in exon 5. In vitro mutagenesis revealed that the Ser '72-*uCys mutation caused a mutant LPL protein that had residual activity higher than that seen in all eight other missense mutations in patients with LPL deficiency identified in our laboratory. We propose that some mutations in the LPL gene produce a defective LPL with partial activity, which usually leads to mild hypertriglyceridemia. (J. Clin. Invest.

Lipoprotein metabolism of pregnant women is associated with both their genetic polymorphisms and those of their newborn children

“…In such cases, it is expected that pregnancy, which is usually associated with increased triglycerides, will severely exacerbate the preexisting hypertriglyceridemia and, consequently, the risk of pancreatitis. It is intriguing, however, to observe that not all women with familial lipoprotein lipase deficiency develop pancreatitis during pregnancy, as has been reported in the literature (49)(50)(51)(52)(53). In our lipid clinics, the three women known to be deficient in lipoprotein lipase had suffered from several episodes of pancreatitis, but never during their pregnancies (five pregnancies in total).…”

A study of lipoprotein lipase gene intron 8 polymorphisms in Chinese Han race essential hypertension patients

“…In 1992, Gotoda et al [5] discovered that polymorphism sites exist in the LPL introns. Later, Ma et al [18] found the polymorphism sites on the 33rd, 37th site of intron 5. These studies have provided sufficient hereditary marks for the chain analysis on the family lacking LPL.…”

Acquired lipoprotein lipase deficiency associated with chronic urticaria. A new etiology for type I hyperlipoproteinemia

“…Physiological changes during puberty include an increase in plasma triglycerides, which is due to the higher levels of sexual hormones, especially estrogens. It has previously been shown that the phenotypic expression of type I hyperlipidemia is modifed by estrogens, and some patients present their first symptoms during pregnancy (19). Bucher et al (20) have recently described the case of a girl compound heterozygote for two missense mutations in the LPL gene with a severe increase in triglyceride plasma concentration during puberty due to a marked accumulation of chylomicrons, without modifications in the VLDL, LDL and HDL values, suggesting that the catabolism of chylomicrons in type I hyperlipoproteinemia is further affected by estrogens.…”