Interaction of the common apolipoprotein C-III (APOC3-482C > T) and hepatic lipase (LIPC-514C > T) promoter variants affects glucose tolerance in young adults. European Atherosclerosis Research Study II (EARS-II)

Both hepatic lipase (HL) and apolipoprotein C-III (apoC-III) influence lipi d metabolism. Common variation in promoters of both genes, LLPC -514C >T an d APOC3 -482C >T; respectively; have been shown to affect plasma lipids and lipoproteins and glucose tolerance. We studied the interaction between bot h variants on parameters of glucose tolerance and lipid metabolism in 714 h ealthy young males participating in the second European Atherosclerosis Res earch Study (EARS-II). Approximately 18% of the subjects were carriers of a t least one rare LIPC and APOC3 allele. These subjects exhibited, after fas ting and oral fat loading, the highest values of triglyceride-rich lipoprot eins, but there was no significant interactive effect on any lipid variable . However, interaction occurred on basal diastolic blood pressure (p = 0.03 6) and, during oral glucose tolerance testing, on peak (p = 0.0065) and are a under the curve for glucose (p = 0.049), and insulin (p = 0.035). This re sulted in the highest diastolic blood pressure and lowest glucose tolerance in carriers of at least one rare allele of both genes. Thus gene:gene inte raction between LIPC and APOC3, even in these healthy young males, leads to changes in parameters that are typically characteristic of Syndrome-X.