Apolipoprotein E isoform polymorphisms are not associated with insulin resistance - The Framingham Offspring Study

OBJECTIVE - Insulin resistance and the apolipoprotein (apo) allele e4 have both been associated with coronary heart disease (CHD). We examined the rel ationship between insulin resistance and apo(e) polymorphisms among partici pants in the Framingham Offspring Study. RESEARCH DESIGN END METHODS- During 1991-1995, subjects underwent a clinica l examination and an oral glucose tolerance test with measurement of fastin g and 2-h glucose, insulin levels, and fasting lipid levels. We measured in sulin resistance using the homeostasis model, in which insulin resistance ( HOMA-IR) = Easting insulin x glucose/22.5. Apo(e) isoforms and phenotypes w ere determined in 1983-1987 using isoelectric focusing of plasma VLDL. Of t he 2,120 subjects with complete HOMA-IR and apo(e) data, 204 with type 2 di abetes were excluded. The remainder were classified with features of the in sulin resistance syndrome including impaired glucose tolerance (1997 Americ an Diabetes Association criteria), hypertension (criteria from the Joint Na tional Committee on Prevention, Detection, Evaluation, and Treatment of Hig h Blood Pressure [6th report]), obesity (BMI >85th percentile), high waist- to-hip ratio (>85th percentile), and high triglyceride and low HDL levels ( NCEP-2 criteria). We analyzed data with contingency tables and age- and sex -adjusted logistic regression models. RESULTS - Among the 1,916 subjects, the mean age was 55 (range 28-83 years) and 51% were women. Median HOMA-IR was 6.4 (interquartile range 5.2-8.2), and allele frequencies were 7.8, 79.9, and 12.4% for apo(e) alleles e2, e3, and e4, respectively There were no differences in proportions of apo(e) is oforms or alleles across increasing quintiles of HOMA-IR. A less dramatic i ncrease in proportions occurred with elevated triglycerides associated with increasing HOMA-IR among those with apo(e) isoforms 2/2 and u3 compared wi th the others (P less than or equal to 0.01 for interaction). Otherwise, ap o(e) did not substantially modify associations between insulin resistance a nd features of the insulin resistance syndrome. CONCLUSIONS - There is no association between apo(e) polymorphisms and insu lin resistance. These appear to represent 2 completely independent risk fac tors for CHD.