Genetic study of common variants at the Apo E, Apo AI, Apo CIII, Apo B, lipoprotein lipase (LPL) and hepatic lipase (LIPC) genes and coronary artery disease (CAD): variation in LIPC gene associates with clinical outcomes in patients with established CAD

Abstract

BackgroundCurrent evidence demonstrates that positive family history and several alterations in lipid metabolism are all important risk factors for coronary artery disease (CAD). All lipid abnormalities themselves have genetic determinants. Thus, objective of this study was to determine whether 6 genetic variants potentially related to altered lipid metabolism were associated with CAD and with lipid abnormalities in an Italian population. These genetic variables were: apolipoprotein E (Apo E), Apo AI, Apo CIII, Apo B, lipoprotein lipase (LPL) and the hepatic lipase (LIPC) genes. Furthermore, an 8 years prospective analysis of clinical cardiovascular events was related to the various genetic markers.Methods102 subjects with established coronary artery disease and 104 unrelated normal subjects were studied. CAD Patients were followed up for 8 years, and clinical CAD outcomes (a second coronary angioplasty (PTCA), myocardial infarction, coronary artery by-pass graft (CABG), cardiovascular deaths), available from 60 subjects, were related to the genetic variants by multiple regression analysis. Results. Of the six lipid loci studied (for a total of 11 polymorphisms) only the apolipoprotein E, Apo B and LIPC polymorphisms distinguished between case and controls. However, multivariate analysis accounting for clinical and metabolic predictors of CAD showed that only the ApoB Xba1 and ApoE4 polymorphism associated with CAD in this Italian population. When lipid parameters were related to genotypes, the ApoE, ApoB, and LIPC gene polymorphisms were associated to various markers of dyslipidaemia in the CAD patients, confirming previous reports. When the occurrence of a second cardiovascular event was related to genotypes, an independent role was observed for the LIPC gene T202T variant.Conclusionsvariation in LIPC (hepatic lipase) gene associates with clinical outcomes in Italian patients with established CAD. Further studies on the LIPC gene in CAD patients are warranted, in particular looking at the possible influences on clinical outcomes.

Alu-repeat Polymorphism in the Tissue Plasminogen Activator Gene and Risks of Myocardial Infarction in Tunisian Population

“…Interestingly total plasma cholesterol did not discriminate between cases and controls as in other European countries [20]. Multiple regression analysis confirmed the independent predictive role for all of the above mentioned lipid parameters [21,22].…”

Polymorphisms in the hepatic lipase gene affect plasma HDL-cholesterol levels in a Turkish population

“…However, although the frequency of the S allele was 33% in Turks, it was not associated with HDL-C levels or hepatic lipase activity. The frequency of T224T was similar in Finnish cases and controls ( 11 ), but was signifi cantly lower in Italian coronary heart disease patients than controls (36% vs. 53%) ( 53 ). This variant was not associated with lipid parameters in Turks.…”

Allelic variation in ApoC3, ApoA5 and LPL genes and first and second generation antipsychotic effects on serum lipids in patients with schizophrenia

“…7,[21][22][23][24] Furthermore, other genes such as the ApoE, ApoA1, ApoB, hepatic lipase and PPAR genes have been investigated for their association with lipid levels and/or cardiovascular disease outcomes. 4,10,[25][26][27] Since weight gain and BMI are significantly correlated with serum triglycerides and cholesterol levels, it is possible that genetic variants which may influence the extent of weight gain during treatment with antipsychotics, such as the polymorphisms in the 5-HT2C receptor (À759 T/C), 28,29 polymorphisms of the leptin gene, 28,30 and polymorphisms in the a2A receptor (À1291 C/G) 31 may also be related to deferential drug  gene effects on serum lipids. In this initial study, we could only investigate a few polymorphisms which previous studies suggested may have significant effects on plasma or serum triglycerides or cholesterol; we also chose SNPs with a minor allele frequency of at least 10% in some prior studies.…”