Apolipoprotein E genotype and cardiovascular disease in the Framingham Heart Study

Background: Apolipoprotein (apo) E is a constituent of lipoproteins with co nsiderable variation due to cysteine-arginine exchanges. The apo E4 (Arg112 -Cys) polymorphism has been associated with dementia and hypercholesterolem ia. We investigated the relation of APOE genotype to cardiovascular disease (CVD) in the Framingham Offspring Study. Methods and results: DNA was isolated from 3413 study participants and APOE genotypes were determined utilizing the polymerase chain reaction and rest riction isotyping. In the entire group of subjects, 20.7% had apo E4/4 or E 3/4 (Group E4), 14.1%, had apo E2/2 or E2/3 (Group E2) and 63.9% had the ap o E3/3 genotype (Group E3). Subjects with E2/4 (1.3%) were excluded. Period prevalence of CVD between examinations 1 and 5 (1971-1994) (366 events) wa s related to APOE genotype. Age adjusted period prevalence of CVD in men wa s 18.6% for Group E4, 18.2%, for Group E2 and 13.7%. For Group E3 (P = 0.00 4): while in women these rates were 9.9. 4.9. and 6.6%. respectively (P = 0 .037). After adjustment for non-lipid risk factors the relative odds for CV D in Group E2 men was 1.79 (P = 0.0098) and in Group E4 it was 1.63 (P = 0. 0086) compared with the Group E3, while in Group E4 women it was 1.56 (P = 0.054). After adjustment for all CVD risk factors, the relative odds in Gro up E2 men was 1.94 (P = 0.004) and in Group E4 men it was 1.51 (P = 0.0262) . Conclusions: The presence of the apo E2 or apo E4 alleles in men is associa ted with significantly greater CVD risk. This genotypic information may hel p to identify individuals at increased risk for CVD events. (C) 2001 Elsevi er Science Ireland Ltd. All rights reserved.