Polymorphisms in the insulin response element of APOC-III gene promoter influence the correlation between insulin and triglycerides or triglyceride-rich lipoproteins in humans.

Abstract

To assess whether the -455 and -482 mutations in APOC-III gene insulin response element affect the relationships between plasma insulin and triglyceride-rich lipoprotein levels. Population-based studies. The population sample was composed of 983 subjects (485 men and 498 women), aged between 35 and 65 y, randomly sampled from the electoral rolls in Northern France and stratified on gender and 10 y age groups. Plasma triglyceride, apolipoprotein C-III, apoB, LpC-III:B and LpE:B lipoprotein particles and insulin levels were measured. Two polymorphisms in APOC-III gene insulin response element (T-->C at -455 and/or C-->T at -482) were determined. Plasma insulin was positively correlated to triglyceride levels (P<0.0001), apo C-III (P<0.003), LpC-III:B (P<0.0001), apoB (P<0.0001) and LpE:B (P<0.0001). This association differed significantly according to APOC-III insulin response element polymorphisms. The relationship between insulin and LpC-III:B (P<0.02) or apoB (P<0.02) was greater in women bearing the C allele of -455 than the T allele. Similarly, the relationship between insulin and LpC-III:B (P<0.02) or LpE:B (P<0.05) was greater in women bearing the T allele of -482 than the C allele. There was no evidence for any effect in men. These results suggest that the relationship between plasma insulin and triglyceride-rich lipoprotein levels is partly influenced by polymorphisms in APOC-III insulin response element.