Italy ranks as one of the lowest in mortality rates for coronary artery disease in Europe , yet many of the conventional risk factors showed significant differences in our patients with coronary artery disease compared to healthy Italian controls. The frequency of smokers was higher in the arterial disease group; and plasma LDL cholesterol, triglycerides, and Lp(a) were also raised in the disease group whereas HDL-cholesterol was reduced. Interestingly total plasma cholesterol did not discriminate between cases and controls as in other European countries . Multiple regression analysis confirmed the independent predictive role for all of the above mentioned lipid parameters.
Of the six lipid loci studied (for a total of 11 polymorphisms) the apolipoprotein E, ApoB and LIPC polymorphisms distinguished between case and controls in univariate analysis. However, multivariate analysis accounting for clinical and metabolic predictors of CAD showed that only Apo E and ApoB Xba1 polymorphisms were independently associated with CAD in this Italian population. This latter result confirms previous association studies where the allele possessing the XbaI site was found to be associated with higher levels of total cholesterol, LDL, apoB and triglycerides, and it was concluded that this genotype confers increased risk of myocardial infarction [5, 20]. Also results on the Apo E gene association confirm previous observations . When lipid parameters were related to genotypes, the ApoE, ApoB and, LIPC gene polymorphisms were associated with various markers of dyslipidaemia in this CAD population, confirming previous reports of the influence of these gene polymorphisms on lipid parameters (reviewed in ).
The most interesting result in our study was the observation that the LIPC (hepatic lipase) gene T202T polymorphisms was independently associated with clinical outcomes in patients with established CAD. Thus, when the occurrence of a second cardiovascular event was related to genotypes, a strong association by multiple logistic regression analysis was observed with the LIPC gene T202T variant. Also this variant was associated with reduced HDL-cholesterol levels in our population. Low hepatic lipase activity has been shown to be associated with an increased risk for CAD . Hepatic lipase is a lipolytic enzyme synthesised in liver cells, and has a dual role in lipid metabolism. It is involved in chylomicron remnant catabolism and in HDL metabolism, influencing hepatic HDL interconversion  from large, cholesterol ester-rich HDL particles to smaller particles that are ready to accept cholesterol from cell membranes. Furthermore, LDL buoyancy and size appear to be inversely associated with hepatic lipase activity levels , and hepatic lipase appears to influence LDL lipid composition by affecting the surface lipid components.
Studies on hepatic lipase enzyme activity show that hepatic lipase deficiency in most cases leads to triglyceride enrichment in LDL and HDL lipoprotein fractions, presence of circulating β-VLDL and abnormal chylomicron catabolism .
A role for the LIPC gene in atherosclerosis and CAD has been proposed by genetic and functional studies [25, 26]. Guerra et al.  examined the relationship between polymorphism in the gene coding for hepatic lipase, using a sequential approach comprising linkage analysis, DNA sequencing and association studies. This study concluded that allelic variation at, or closely linked to, the LIPC gene accounts for about 25% of the plasma HDL-cholesterol variation in concentrations. Moennig et al.  sequenced the LIPC gene in patients with low HDL/high triglycerides and CAD, and their results suggested that mutations in LIPC may play a role in the pathogenesis of atherosclerosis. The polymorphism that we have studied (T202T) has been shown to be in linkage disequilibrium with other LIPC gene polymorphisms: L334F, T457T (linkage disequilibrium coefficients were -1.00 and -0.96, respectively) and weakly to-C480T , also described as C-514T. This latter polymorphism was reported associated with a lower hepatic lipase activity in CAD patients . This observation has been subsequently confirmed , suggesting that the common LIPC promoter variant-C480T is functional and associated with an impaired hepatic lipase activity influencing lipoproteins metabolism. Furthermore, hepatic lipase enzyme with the L334F variant was shown in in vitro expression studies to have only about 30% of the enzymatic activity of the wild-type enzyme . It is thus possible that the T202T variant, which is one of the more common polymorphisms of LIPC gene, is a simple marker of one of the other LIPC variants, considering also that it is in linkage disequilibrium with these other polymorphisms and in particular with the L334F variant. We acknowledge that our sample was small, and these results should be considered preliminary, although an 8 years follow up is long enough to determine clinical outcomes. Moreover, several reports have demonstrated an important role for the LIPC gene in the risk of CAD and its related lipid abnormalities. Low HDL-cholesterol and LDL subclass distribution, both influenced by hepatic lipase activity, have been shown to be strong risk factors for early atherosclerosis [23, 31]. Thus, further studies on sequence variations of the LIPC gene in CAD patients are warranted, in particular looking at the possible influences on clinical outcomes. The possibility to predict by genetic analysis the risk of progression of coronary atherosclerotic lesions would be of great importance for the management of CAD patients.