Apolipoprotein E polymorphism and atherosclerosis: association of the epsilon4 allele with defects in the internal elastic lamina

The defects in the internal elastic lamina (IEL) have been proposed to be important for the migration of smooth muscle cells into the intima during atherosclerosis. We investigated the association of a genetic factor--apolipoprotein E (apoE) genotype--with the number of gaps in the IEL of the artery wall in 123 consecutive autopsy cases (90 male, 33 female) aged 18-93. At autopsy, the circumference of the IEL and the number of gaps in the IEL were measured in circular samples of the coeliac; (CA), superior mesenteric (SMA) and inferior mesenteric (IMA) arteries. In the series, the number of gaps per millimetre in the IEL of CA, SMA and IMA were associated with intimal thickening (P<0.0001, P=0.01 and P=0.005, respectively). In men, apoE genotype was significantly associated with the number of gaps in the IEL of the CA and IMA (P=0.033 and P=0.041, respectively). The carriers of epsilon4/3 or epsilon4/4 genotype had higher number of gaps in CA than the carriers of epsilon3/3 genotype (2.30+/-2.63 vs. 1.38+/-1.83 gaps/mm, P=0.035) and also higher number of gaps in IMA than the carriers of epsilon3/2 (2.18+/-1.71 vs. 0.66+/-0.60 gaps/mm, P=0.041). The results suggest that the apoE varepsilon4 allele may be involved with IEL fragmentation in men. This may be mediated through higher serum cholesterol associated with the varepsilon4 allele.