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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.

Polymorphisms in the Apolipoprotein E Gene Regulatory Region in Relation to Coronary Heart Disease and Their Effect on Plasma Apolipoprotein E