title: Apolipoprotein E epsilon4 genotype is independently associated with increased intima-media thickness in a recessive pattern.
abstract: Polymorphisms in the apolipoprotein E (Apo E) gene have been associated with lipid levels, carotid intima media thickness (CCA-IMT), inflammation and cardiovascular disease (CVD). Earlier findings suggested an association of the Apo E alleles with increased CCA-IMT following a recessive pattern. Whether associations might be independent of C-reactive protein (CRP), lipid levels and other CVD risk factors is not known. We investigated the relationships between Apo E (epsilon2, epsilon3 and epsilon4 alleles) and CCA-IMT, measured by B-mode ultrasound, in dominant and recessive models in a community-based sample of 437 men 75 years of age. In men homozygous for the epsilon4 allele CCA-IMT was significantly increased by 0.13 mm to 0.86 +/- 0.16 mm compared to 0.73 +/- 0.19 mm in non- epsilon4-carriers (P = 0.0012) and 0.73 +/- 0.21 mm in epsilon4 heterozygous (P = 0.0044) in unadjusted recessive models. The association between Apo E epsilon4 genotype and CCA-IMT was independent of Apo E epsilon2 and Apo E epsilon3 alleles, CRP, lipid variables (TG, LDL, HDL) and other CVD risk factors (smoking, hypertension, body mass index, diabetes) (P = 0.018). No relations between Apo E genotype and CCA-IMT were observed in dominant models. No significant associations between the Apo E epsilon2 and epsilon3 alleles and CCA-IMT were found. In this study, men homozygous with the ApoE epsilon4 allele had thicker CCA-IMT, independently of Apo E epsilon2 and epsilon3 alleles, CRP, lipid variables (TG, LDL, HDL) and other CVD risk factors (smoking, hypertension, body mass index, diabetes), suggesting CCA-IMT to be modified by the ApoE epsilon4 genotype in a recessive pattern.
authors.affiliation: Department of Public Health and Caring Sciences/Geriatrics and Clinical Nutrition, Faculty of Medicine, Uppsala University, Uppsala Science Park, 751 85, Uppsala, Sweden. martin.wohlin@pubcare.uu.se
authors.forename: M
authors.initials: M
authors.lastname: Wohlin
authors.forename: J
authors.initials: J
authors.lastname: Sundström
authors.forename: Lars
authors.initials: L
authors.lastname: Lannfelt
authors.forename: Tomas
authors.initials: T
authors.lastname: Axelsson
authors.forename: A C
authors.initials: AC
authors.lastname: Syvänen
authors.forename: B
authors.initials: B
authors.lastname: Andrén
authors.forename: S
authors.initials: S
authors.lastname: Basu
authors.forename: L
authors.initials: L
authors.lastname: Lind
mesh_terms: D000368:Aged; D000483:Alleles; D053327:Apolipoprotein E4 / Q000097:blood / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000378:metabolism; D002339:Carotid Arteries / Q000000981:diagnostic imaging*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D012307:Risk Factors; D017539:Tunica Intima / Q000000981:diagnostic imaging; D017540:Tunica Media / Q000000981:diagnostic imaging; D014463:Ultrasonography
chemical_list: D053327:Apolipoprotein E4