Affiliations: Laboratory of Molecular Investigation, University
Hospital Miguel Servet, Aragonian Health Sciences Institute, Zaragoza, Spain | Department of Biochemistry and Molecular and Cellular
Biology, University of Zaragoza, Zaragoza, Spain | Division of Neurology, Hospital Virgen del Camino,
Pamplona, Spain | Division of Internal Medicine, University Hospital
Miguel Servet, Zaragoza, Spain
Note: [] Corresponding author: Marta Artieda, Laboratorio de
Investigación Molecular, Hospital Universitario Miguel Servet, Isabel la
Católica, 1-3, 50009 Zaragoza, Spain. Tel.: +34 976 765500 Ext. 3481; Fax:
+34 976 76566569; E-mail: martieda@salud.aragon.es
Abstract: Background: Apolipoprotein E (apo E) plays a major role in lipid
metabolism, and its genetic variations have been associated with cardiovascular
risk. The objective of this study was to investigate the influence of the
APOE promoter (−491 A/T, −427 T/C and −219 G/T) and coding
region (APOE ε2/ε3/ε4) polymorphisms in
atherosclerosis disease by association and linkage disequilibrium analyses.
Materials and methods: We analyzed these polymorphisms in a sample of 286
subjects with atherosclerosis disease: 153 subjects with atherothrombotic
stroke (ATS) and 133 subjects with ischemic heart disease (IHD); and in two
control groups, 103 newborns and 114 elderly subjects. Results: The
ε4 allele was associated with more severe carotid stenosis in the
ATS group, being the percentages of ε4 carriers 26.7% and
11.4% for the higher and lower carotid stenosis groups, respectively
(p=0,066). The −491 T/T IHD subjects presented higher vessel scores than
subjects A/A and A/T genotypes at that position (p=0,041), and the
frequencies of −2 (5.1% versus 14.1%, p=0,060) and −427C
(10.3% versus 24.4%, p=0,019) alleles were lower in IHD subjects with
higher extent score versus lower extent score. The ε2 allele was
in linkage disequilibrium with the −427C allele in all studied groups, and
the −219T allele was associated with the ε4 allele in the IHD
group. Conclusion: In summary, the ε2 allele was in linkage
disequilibrium with the −427C allele in all studied groups, and only slight
associations between the analyzed APOE polymorphisms in the promoter and in the
coding region and carotid and coronary vascular disease have been observed.
Keywords: Apolipoprotein E, atherosclerosis, atherothrombotic stroke, ischemic heart disease, polymorphisms
