Abstract P194: Gene-Environment Interactions and Blood Lipid levels: a Twin Study

Abstract

Genetic variation may affect blood lipid levels by directly determining levels (‘level genes’) and/or by influencing the response to environmental factors (‘variability genes’), i.e. gene-environment interaction. Previous dietary studies assessing variability gene effects have produced inconsistent results, perhaps due to a lack of statistical power, different dietary protocols, and/or differences in the age, sex, habitual diet, baseline lipid values and other genes of the participants. Monozygotic (MZ) twins can enhance our ability to identify variability genes because they are genetically identical and also share the same age, sex and aspects of their early environment. Therefore, all intrapair differences in blood lipid levels are due to environmental factors such as diet and lifestyle, and variation between genotypes in intrapair differences will indicate the existence of variability genes. We investigated the hypothesis that polymorphisms within the genes for apoB, apoE and lipoprotein lipase influence the blood lipid response to environmental factors. The subjects studied were 64 MZ male and female twin pairs aged 18-75 years who had been recruited for a study of coronary heart disease risk factors in twins. Blood samples already taken for analysis of fasting lipid levels were used for DNA extraction. Genotypes were determined for the polymorphisms apoB signal peptide insertion/deletion (I/D), apoB Xba I, apoE, and lipoprotein lipase Pvu II, Hind III and S447X. Mean intrapair differences in lipid levels adjusted for mean twin pair lipid level were calculated for each genotype group. In MZ twins, carriers of the apoB signal peptide D allele had smaller intrapair differences in total cholesterol (p=0.044) but larger intrapair differences in apoAI (p=0.035) than I/I twins, and apoE ε4 carriers had smaller intrapair differences in HDL-cholesterol than E3/3 and E3/2 twins (p=0.024). MZ twins with the Pvu II P-P- genotype had significantly greater intrapair differences in apoB than P-P+ or P+P+ twins. The Xba I, Hind III and S447X polymorphisms did not influence intrapair differences in lipid levels. In conclusion, the apoB signal peptide I/D, apoE and lipoprotein lipase Pvu II polymorphisms may act as variability genes and influence the susceptibility of blood lipid levels to dietary and pharmacological interventions for dyslipidaemia. The approach of using MZ twins to identify variability genes can be applied to other phenotypes, prior to determining the environmental factors that interact with the genes to influence the phenotype.