Apolipoprotein E e4 allele affects risk of hyperhomocysteinemia in the elderly.
BACKGROUND
Apolipoprotein E (APOE) plays a central role in VLDL metabolism. Both APOE e4 allele (APOE4) and C-reactive protein (CRP) are associated with greater risk of dementia and vascular disease, but APOE4 carriers have lower blood concentrations of CRP than do noncarriers, possibly through a mechanism favoring the clearance of the CRP VLDL-bound fraction. Homocysteine, another risk factor for vascular disease and dementia, also binds to VLDL in blood. However, the association between APOE4 and hyperhomocysteinemia has never been thoroughly investigated.


OBJECTIVE
We investigated in an elderly population whether 1) APOE4 is associated with hyperhomocysteinemia [plasma total homocysteine (tHcy) > 15 micromol/L], 2) hyperhomocysteinemia affects the association between APOE4 and high CRP (serum CRP > 3 mg/L), and 3) B vitamin status affects these associations.


METHODS
APOE4 genotypes were assessed and tHcy, CRP, and serum concentrations of folate and vitamin B-12 were measured in 671 cognitively healthy subjects (52% women; mean age: 73 y) from an Italian population-based prospective cohort study.


RESULTS
APOE4 carriers without high CRP [multivariate-adjusted odds ratio (OR): 0.22; 95% CI: 0.08, 0.59] had a lower risk of hyperhomocysteinemia than did noncarriers. The risk of high CRP was lower in APOE4 carriers without hyperhomocysteinemia (multivariate-adjusted OR: 0.51; 95% CI: 0.31, 0.85) than in noncarriers. The associations were not affected by B vitamin status.


CONCLUSIONS
Independently from B vitamin status, APOE4 carriers have a lower risk of hyperhomocysteinemia and of high CRP than do noncarriers, but the presence of one condition attenuates the association of APOE4 with the other condition.
Ravaglia
Giovanni
G
Department of Internal Medicine, Cardioangiology, and Hepatology, University Hospital S Orsola-Malpighi, Bologna, Italy. ravaglia@med.unibo.it
Forti
Paola
P
Maioli
Fabiola
F
Chiappelli
Martina
M
Montesi
Fausta
F
Bianchin
Marisa
M
Licastro
Federico
F
Patterson
Christopher
C
D000368:Aged; D000375:Aging / Q000097:blood* / Q000502:physiology / Q000523:psychology; D000483:Alleles; D053327:Apolipoprotein E4 / Q000235:genetics*; D002097:C-Reactive Protein / Q000378:metabolism*; D015331:Cohort Studies; D016001:Confidence Intervals; D003704:Dementia / Q000097:blood / Q000453:epidemiology / Q000209:etiology; D005260:Female; D005838:Genotype; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000097:blood / Q000453:epidemiology*; D008079:Lipoproteins, VLDL / Q000378:metabolism; D008297:Male; D016017:Odds Ratio; D011446:Prospective Studies; D012307:Risk Factors; D014652:Vascular Diseases / Q000097:blood / Q000453:epidemiology / Q000209:etiology
D053327:Apolipoprotein E4; D008079:Lipoproteins, VLDL; D006710:Homocysteine; D002097:C-Reactive Protein