APOC3 ­482C>T polymorphism, circulating apolipoprotein C-III and smoking: Interrelation and roles in predicting type-2 diabetes and coronary disease

ObjectivesWe determined the relationship of smoking status on APOC3 ­482C>T polymorphism and apolipoprotein C-III (apoC-III) concentrations and the latter two parameters’ influence on risk of diabetes and coronary heart disease (CHD).Design and methodsPrediction of incident cases was assessed at 5.5 years’ follow-up in unselected 519 individuals of a general population genotyped for ­482C>T polymorphism.ResultsFemale sex and current smoking were significantly associated with low circulating apoC-III in subjects without (p ≤ 0.033) than with abdominal obesity (p = 0.053) or than insulin resistant ­482TT homozygotes (p = 0.034) who had 20–30% higher serum apoC-III. Multi-adjusted serum apoC-III was log-linearly associated with fasting triglycerides. ApoC-III levels determined the development of diabetes [RR 1.56 (95%CI 1.21; 2.01)] and CHD [RR 1.38 (1.10; 1.72) for an increment of 14%], after adjustment for confounders.ConclusionAPOC3 ­482TT genotype is associated with high apoC-III concentrations only in the presence of abdominal obesity or insulin resistance, but not in current smokers who remain lean or insulin-sensitive. Rather than APOC3 ­482C>T polymorphism, circulating apoC-III determines cardiometabolic risk.