Heterozygous Lipoprotein Lipase Deficiency

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 Gly 188 →Glu and Ile 194 →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 Gly 188 →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 Gly 188 →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 Gly 188 →Glu substitution were more pronounced than those of the common Asn 291 →Ser substitution. Conclusions Heterozygous lipoprotein lipase deficiency due to the Gly 188 →Glu substitution appears to increase plasma triglycerides and reduce HDL levels and may thereby predispose carriers to ischemic heart disease.