Obesity modulates the association among APOE genotype, insulin, and glucose in men.
OBJECTIVE
Obesity, insulin resistance, and apolipoprotein E (APOE) genotype have all been associated with coronary heart disease. We examined the interaction between obesity and APOE genotype in determining fasting insulin and glucose levels.


METHODS
From 1991 to 1995, 3799 subjects underwent a clinical examination and fasting insulin and glucose measurement. APOE genotypes were determined on 3500 participants. Participants taking oral hypoglycemic drugs or insulin preparations or with the rare APOE2/4 genotype were excluded. Finally, 2929 individuals were included in the present analysis.


RESULTS
In men, we observed a statistically significant interaction between obesity and APOE genotype on insulin and glucose level (p = 0.003 and 0.008, respectively). Obese men with the APOE4 genotype presented with higher levels of insulin and glucose than obese men in the other genotype groups. No association between genotype and insulin or glucose in nonobese men was observed. Obesity was associated with higher insulin levels in the three APOE genotypes groups, whereas obesity was directly associated with glucose in those with the APOE4 genotype. In women, the effect of interaction between APOE genotype and obesity on fasting insulin and glucose was not statistically significant. Obesity was associated with higher levels of fasting insulin and glucose. APOE genotype was not associated with insulin or glucose.


CONCLUSIONS
Obesity modulates the association between the APOE genotype and fasting insulin and glucose levels in men. Although weight control is important in all people, it may be especially important in APOE4 men to modify potentially elevated fasting insulin and glucose levels.
Elosua
Roberto
R
Nutrition and Genomics Laboratory and Lipid Metabolism Laboratory, Jean Mayer-U.S. Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts 02111, USA.
Demissie
Serkalem
S
Cupples
L Adrienne
LA
Meigs
James B
JB
Wilson
Peter W F
PW
Schaefer
Ernst J
EJ
Corella
Dolores
D
Ordovas
Jose M
JM
D001057:Apolipoproteins E / Q000235:genetics*; D001786:Blood Glucose / Q000378:metabolism*; D004247:DNA / Q000737:chemistry / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007328:Insulin / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood* / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012737:Sex Factors
D001057:Apolipoproteins E; D001786:Blood Glucose; D007328:Insulin; D004247:DNA