Both hepatic lipase (HL) and apolipoprotein C-III (apoC-III) influence lipid metabolism. Common
variation in promoters of both genes, LIPC -514C > T and APOC3 -482C > T, respectively, have
been shown to affect plasma lipids and lipoproteins and glucose tolerance. We studied the interaction
between both variants on parameters of glucose tolerance and lipid metabolism in 714 healthy young
males participating in the second European Atherosclerosis Research Study (EARS-II). Approximately
18% of the subjects were carriers of at least one rare LIPC and APOC3 allele. These subjects
exhibited, after fasting and oral fat loading, the highest values of triglyceride-rich lipoproteins, but
there was no significant interactive effect on any lipid variable. However, interaction occurred on
basal diastolic blood pressure (p =0.036) and, during oral glucose tolerance testing, on peak (p =
0.0065) and area under the curve for glucose (p =0.049), and insulin (p = 0.035). This resulted in
the highest diastolic blood pressure and lowest glucose tolerance in carriers of at least one rare allele
of both genes. Thus gene:gene interaction between LIPC and APOC3, even in these healthy young
males, leads to changes in parameters that are typically characteristic of Syndrome-X.