THE EFFECTS OF GENOTYPE AND INFANT WEIGHT ON ADULT PLASMA-LEVELS OF FIBRINOGEN, FACTOR-VII, AND LDL CHOLESTEROL ARE ADDITIVE

High circulating levels of cholesterol, particularly low density lipop rotein (LDL) cholesterol and the clotting factors fibrinogen and facto r VII, are associated with increased risk of myocardial infarction. Va riations in the plasma levels of these factors are determined in part by polymorphisms in the genes concerned and also by weight at 1 year ( infant weight). We have looked at the possibility of interactions betw een these genetic factors and infant weight in a sample of 290 men and 192 women from Hertfordshire using the beta-fibrinogen G/A(-455), fac tor VII R353Q, and ApoE polymorphisms. The rare allele frequencies of the three polymorphisms were 0.19 for beta-fibrinogen, 0.10 for factor VII, and 0.07 and 0.13 for the 2 and 4 alleles of ApoE, and these fre quencies were not different in subjects of different infant weight. In this sample, the polymorphisms showed the expected effects on plasma levels of fibrinogen, factor VII, and LDL cholesterol. The A(-455) all ele was associated with higher fibrinogen levels but the effect was on ly statistically significant in women (p=0.003). The R353 allele was a ssociated with higher factor VII activity in both men and women (p<0.0 001 for both). The ApoE2 allele was associated with lower levels of LD L cholesterol (p=0.03 in men, p=0.006 in women), while the ApoE4 allel e was associated with higher levels (p<0.001 in men, not significant i n women). In this sample of men and women the effect of low infant wei ght was only associated with significant effects on fibrinogen and LDL cholesterol in the group of men (p=0.005 and p=0.008 respectively). C ompared with the E3E3 subjects, the LDL lowering effect of the E2 alle le and the raising effect of the E4 allele was greater in those with l ow infant weight compared with those with high infant weight (low v hi gh infant weight for E2: 12,7% v 9.4%; for E4 12.7% v 8.5%). Although in this sample the interactive effect did not reach statistical signif icance, the additive effect of ApoE genotype and low infant weight on determining plasma LDL cholesterol levels, if confirmed, may be of rel evance in determining a person's future risk of atherosclerosis.