Polymorphisms in the apolipoprotein E gene regulatory region in relation to coronary heart disease and their effect on plasma apolipoprotein E.
In a previous study which examined the distribution of apolipoprotein E genotypes and plasma levels in a sample of male coronary heart disease (CHD) patients and controls, we found a significant excess of the genotypes carrying APOE*4 allele in CHD men (18.2%) vs. controls (9.6%) and an association between the APOE*4 allele and the lowest concentrations of apoE. In the present investigation, we re-examined in the same samples two recently identified polymorphisms in the promoter region of APOE, -491A/T and -427T/C, which may alter the level of apoE expression. No differences in the distributions of the -491A/T genotypes and alleles were observed between cases and controls (-491*A = 0.760 and 0.757 respectively). Polymorphism -427T/C showed in CHD patients an excess of -427*C allele (patients vs. controls = 0.123 vs. 0.074) and corresponding genotypes that was marginally significant. Stratification of the samples according to the presence/absence of APOE*4 showed that the excess of the -427*C allele concerned only CHD patients not carrying APOE*4 allele (patients vs. controls = 0.133 vs. 0.061; p=0.017). This result suggests that the presence of -427*C allele could represent a risk for developing CHD in subjects with E2/E2, E3/E2, and E3/E3 genotypes. Studies carried out on patients with Alzheimer's disease demonstrated that -491A/T and -427T/C polymorphisms affect the level of plasma apoE. In the present study, carried out on CHD patients and controls, the genetic variation at -427 and -491 sites of the APOE regulatory region had no apparent effect on apoE plasma concentration.
Department of Genetics and Molecular Biology, La Sapienza University, Rome, Italy. Corbo@axcasp.caspur.it
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D000367:Age Factors; D000368:Aged; D000483:Alleles; D000787:Angina Pectoris / Q000097:blood / Q000235:genetics; D001057:Apolipoproteins E / Q000097:blood* / Q000235:genetics*; D016022:Case-Control Studies; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D003327:Coronary Disease / Q000097:blood* / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000235:genetics; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood
D001057:Apolipoproteins E; D008076:Cholesterol, HDL; D014280:Triglycerides; D002784:Cholesterol