September 16, 1997
Ver artículo completoHeterozygous Lipoprotein Lipase Deficiency
Resultado clave
The heterozygous Gly188-->Glu substitution was more common among patients with ischemic heart disease than the general population (0.32% vs 0.06%; OR 4.9; 95% CI 1.2-19.6).
Diseño del estudio
Tipo
Case-Control (n=10,207)
PICO estructurado
Does heterozygous lipoprotein lipase deficiency increase the risk of ischemic heart disease and alter lipid profiles?
P
Población
10,207 individuals, comprising 9,259 from a general population sample and 948 patients with verified ischemic heart disease, screened for lipoprotein lipase mutations.
E
Exposición
Heterozygous carrier status for lipoprotein lipase mutations (Gly188-->Glu and Ile194-->Thr)
C
Comparador
Non-carriers in the general population
O
Resultado
Frequency of mutations, lipid levels (triglycerides, HDL cholesterol, apo A-I, glucose), and risk of ischemic heart diseasehard clinical
Heterozygous lipoprotein lipase deficiency due to the Gly188-->Glu substitution increases plasma triglycerides, reduces HDL, and is associated with a nearly 5-fold increased risk of ischemic heart disease.
Resultado numérico
Odds Ratio: 4.9 (95% CI 1.2–19.6)
Tasa de eventos absoluta: 0.32% vs 0.06%
Resumen
BACKGROUND: Patients with mutations on both alleles of the lipoprotein lipase gene resulting in complete lipoprotein lipase deficiency exhibit the chylomicronemia syndrome with severe hypertriglyceridemia and increased risk of pancreatitis and possibly of ischemic heart disease. This study examined frequency, lipid levels, and risk of ischemic heart disease for heterozygous carriers of lipoprotein lipase mutations known to cause the chylomicronemia syndrome in the homozygous state. METHODS AND RESULTS: Two mutations were screened for in 9259 individuals in a general population sample and in 948 patients with verified ischemic heart disease. The percent frequencies of heterozygous individuals with the Gly188-->Glu and Ile194-->Thr substitutions in the general population were 0.06% (95% CI, 0.04% to 0.23%) and 0% (95% CI, 0.00% to 0.12%), respectively. The Gly188-->Glu substitution was associated with an increase in plasma triglycerides of 0.8+/-0.3 mmol/L (mean+/-SEM) and a decrease in plasma HDL cholesterol, apo A-I, and glucose levels of 0.45+/-0.07 mmol/L, 17+/-6 mg/dL, and 1.1+/-0.2 mmol/L, respectively. On multiple logistic regression analysis allowing for age, sex, plasma cholesterol, plasma lipoprotein (a), hypertension, diabetes mellitus, smoking, and body mass index, both plasma triglycerides and HDL cholesterol levels were independent predictors of ischemic heart disease. Finally, the Gly188-->Glu substitution was more common among patients with verified ischemic heart disease (percent frequency of heterozygous individuals, 0.32%) than among individuals from the general population (odds ratio, 4.9; 95% CI, 1.2 to 19.6). The effects of the Gly188-->Glu substitution were more pronounced than those of the common Asn291-->Ser substitution. CONCLUSIONS: Heterozygous lipoprotein lipase deficiency due to the Gly188-->Glu substitution appears to increase plasma triglycerides and reduce HDL levels and may thereby predispose carriers to ischemic heart disease.