The common mutations in the lipoprotein lipase gene in Italy: effects on plasma lipids and angiographically assessed coronary atherosclerosis

The present study evaluated the role of the common lipoprotein lipase (LPL) mutations on the risk of dyslipidemia and coronary atherosclerosis in an Italian population. Cohorts of 632 patients undergoing coronary angiography, as well as 191 healthy controls, were screened by a combination of PCR and restriction enzyme digestion. In the pooled population, the frequencies of LPL D9N and N291S were 4.1%, with no homozygous carriers, whereas that of LPL S447X was 21% with 19.6% heterozygous and 1.4% homozygous carriers. Compared to non‐carriers, LPL N291S carriers showed higher plasma triglycerides (TG) (p<0.03) and increased risk of high TG phenotype (odds ratio [OR] 2.49, 95% CI 1.06–5.81; p<0.03). When this LPL mutation was associated with high body mass index (BMI) (>25 Kg/m2) or fasting, plasma insulin (>10.6 mU ml−1) significantly reduced HDL‐C levels were also observed. Carriers of the S447X mutation presented with higher HDL‐C concentrations (p<0.05) as compared to non‐carriers; they also showed a significantly reduced risk of high TG/low HDL‐C dyslipidemia (OR 0.34, 95% CI 0.12–0.99; p<0.05). The favourable effect of the LPL S447X variant was even more pronounced in lean subjects and in those with low insulin levels. No significant influence on plasma lipids by the LPL D9N was observed. None of LPL variants was a significant predictor of angiographically assessed coronary atherosclerosis. At most, the risk was borderline, increased in N291S carriers and possibly decreased in S447X carriers.

[1]  J. Hokanson,et al.  Functional variants in the lipoprotein lipase gene and risk cardiovascular disease. , 1999, Current opinion in lipidology.

[2]  B. Nordestgaard,et al.  Lipoprotein Lipase Mutations, Plasma Lipids and Lipoproteins, and Risk of Ischemic Heart Disease A Meta-Analysis , 1999 .

[3]  P. Wilson,et al.  A common truncation variant of lipoprotein lipase (Ser447X) confers protection against coronary heart disease: the Framingham Offspring Study , 1999, Clinical genetics.

[4]  A. Montali,et al.  The gln-Arg192 polymorphism of human paraoxonase gene is not associated with coronary artery disease in italian patients. , 1998, Arteriosclerosis, thrombosis, and vascular biology.

[5]  M. Hayden,et al.  A common mutation in the lipoprotein lipase gene (N291S) alters the lipoprotein phenotype and risk for cardiovascular disease in patients with familial hypercholesterolemia. , 1998, Circulation.

[6]  S. Humphries,et al.  Common variation in the lipoprotein lipase gene: effects on plasma lipids and risk of atherosclerosis. , 1997, Atherosclerosis.

[7]  J. Boer,et al.  Lipoprotein lipase variants D9N and N291S are associated with increased plasma triglyceride and lower high-density lipoprotein cholesterol concentrations: studies in the fasting and postprandial states: the European Atherosclerosis Research Studies. , 1997, Circulation.

[8]  P. Schnohr,et al.  A common substitution (Asn291Ser) in lipoprotein lipase is associated with increased risk of ischemic heart disease. , 1997, The Journal of clinical investigation.

[9]  J. Boer,et al.  Ser447stop mutation in lipoprotein lipase is associated with elevated HDL cholesterol levels in normolipidemic males. , 1997, Arteriosclerosis, thrombosis, and vascular biology.

[10]  M. Hayden,et al.  A frequently occurring mutation in the lipoprotein lipase gene (Asn291Ser) results in altered postprandial chylomicron triglyceride and retinyl palmitate response in normolipidemic carriers. , 1996, Journal of lipid research.

[11]  S. Humphries,et al.  Association between the LPL-D9N mutation in the lipoprotein lipase gene and plasma lipid traits in myocardial infarction survivors from the ECTIM Study. , 1996, Atherosclerosis.

[12]  T. Olivecrona,et al.  Triglyceride lpases and atherosclerosis , 1995 .

[13]  A. Hamsten,et al.  Interaction of the lipoprotein lipase asparagine 291-->serine mutation with body mass index determines elevated plasma triacylglycerol concentrations: a study in hyperlipidemic subjects, myocardial infarction survivors, and healthy adults. , 1995, Journal of lipid research.

[14]  G. Assmann,et al.  The low down on lipoprotein lipase , 1995, Nature Genetics.

[15]  S. Humphries,et al.  A common variant in the gene for lipoprotein lipase (Asp9→Asn) : functional implications and prevalence in normal and hyperlipidemic subjects , 1995 .

[16]  P. Elwood,et al.  DNA variants at the LPL gene locus associate with angiographically defined severity of atherosclerosis and serum lipoprotein levels in a Welsh population. , 1994, Arteriosclerosis and thrombosis : a journal of vascular biology.

[17]  P. Elwood,et al.  Plasma triglyceride and high density lipoprotein cholesterol as predictors of ischaemic heart disease in British men , 1992, British heart journal.

[18]  K. Shirai,et al.  A heterozygous mutation (the codon for Ser447----a stop codon) in lipoprotein lipase contributes to a defect in lipid interface recognition in a case with type I hyperlipidemia. , 1992, Biochemical and biophysical research communications.

[19]  G. Bengtsson-Olivecrona,et al.  Lipoprotein lipase enhances the binding of chylomicrons to low density lipoprotein receptor-related protein. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[20]  A. Gotto,et al.  High density lipoprotein2. Relationship of the plasma levels of this lipoprotein species to its composition, to the magnitude of postprandial lipemia, and to the activities of lipoprotein lipase and hepatic lipase. , 1987, The Journal of clinical investigation.