Relationship between common lipoprotein lipase gene sequence variants, hyperinsulinemia, and risk of ischemic heart disease: A population-based study

Abstract

Objective Hyperinsulinemia and lipoprotein lipase (LPL) are important determinants of fasting and postprandial plasma triglyceride levels. High insulin and high triglyceride levels are associated with an increased risk of ischemic heart disease (IHD). This study aimed to find out whether common LPL gene sequence variants could change the relationship between insulin and IHD. Methods This investigation was a prospective population-based study of 2265 women and men, age 41–72 years, without major cardiovascular diseases and diabetes at baseline. At baseline, IHD risk factors, including fasting levels of plasma glucose and serum insulin, were measured, and carrier status for the two common LPL gene sequence variants: 447X and 291Ser, was determined. Results Of the 2265 participants, 19.9% had the 447X variant and 4.9% had the 291Ser variant. Over a median follow-up of 12.6 years, incidence of IHD (fatal and non-fatal) amounted to 169 events. In proportional-hazard models, adjusted for age, sex, smoking, hypertension, and hypercholesterolemia, hyperinsulinemia, defined as the highest sex-specific insulin quartile, was significantly associated with incident IHD with a hazard ratio (95% confidence interval) of 1.44 (1.05–1.98), P = 0.025, without the LPL variants in the model, and a hazard ratio of 1.42 (1.03–1.95), P = 0.031, with the LPL variants included in the model. In addition, we found no interactions between insulin and the LPL variants and IHD risk ( P > 0.21). Conclusion The relationship between hyperinsulinemia and IHD risk was not changed significantly by common LPL gene sequence variants.