title: Apolipoprotein E genotype and the cardiovascular disease risk phenotype: impact of sex and adiposity (the FINGEN study).
abstract: Here the impact of APOE genotype on CHD risk in UK adults is reported, along with an analysis of APOE genotype × BMI/age/sex interactions. APOE genotype had a significant impact on fasting total:LDL-cholesterol (TC:LDL-C) ratio, triglycerides, % HDL3, and the Framingham 10-year CVD risk score (P<0.05), with an overall trend towards lower and higher risk in E2- and E4-carriers, respectively, relative to the wild-type E3/E3 genotype. A greater impact of genotype on TC:HDL-C was observed in females, which explained 16% of the variability in this outcome versus 6% in males. APOE genotype was also associated with plasma C-reactive protein and adhesion molecule concentrations (P<0.05), with significant genotype × BMI interactions observed. Our observations indicate that the association between the APOE genotype and CHD risk is unlikely to be homogenous and highlights the risk of inaccurate estimations of genotype-phenotype associations in population subgroups without appropriate stratification for sex and adiposity.
authors.affiliation: Hugh Sinclair Unit of Human Nutrition, Department of Food and Nutritional Sciences, University of Reading, Reading RG6 6AP, United Kingdom.
authors.forename: Bettina M
authors.initials: BM
authors.lastname: Kofler
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Miles
authors.forename: Peter
authors.initials: P
authors.lastname: Curtis
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Armah
authors.forename: Sabine
authors.initials: S
authors.lastname: Tricon
authors.forename: Jilly
authors.initials: J
authors.lastname: Grew
authors.forename: Frances L
authors.initials: FL
authors.lastname: Napper
authors.forename: Leslie
authors.initials: L
authors.lastname: Farrell
authors.forename: Georg
authors.initials: G
authors.lastname: Lietz
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Packard
authors.forename: Muriel J
authors.initials: MJ
authors.lastname: Caslake
authors.forename: John C
authors.initials: JC
authors.lastname: Mathers
authors.forename: Christine M
authors.initials: CM
authors.lastname: Williams
authors.forename: Philip C
authors.initials: PC
authors.lastname: Calder
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Minihane
mesh_terms: D050154:Adiposity / Q000235:genetics*; D000328:Adult; D000367:Age Factors; D001057:Apolipoproteins E / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000032:analysis; D002318:Cardiovascular Diseases / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D015815:Cell Adhesion Molecules / Q000097:blood; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D012737:Sex Factors; D014280:Triglycerides / Q000097:blood; D006113:United Kingdom
chemical_list: D001057:Apolipoproteins E; D015415:Biomarkers; D015815:Cell Adhesion Molecules; D008078:Cholesterol, LDL; D018836:Inflammation Mediators; D014280:Triglycerides; D002097:C-Reactive Protein; D002784:Cholesterol