Genetic and Environmental Influences on Lipids, Lipoproteins, and Apolipoproteins

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Abstract
Objective — Levels of lipids and (apo)lipoproteins are known to increase after menopause, but it is unknown whether the genetic and environmental variability alters or whether lipids and (apo)lipoproteins are influenced by different genes before and after menopause. Methods and Results — We studied 453 monozygotic and 1280 dizygotic pairs of female white twins recruited from the St. Thomas’ UK Adult Twin Registry and measured total cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL), triglycerides, lipoprotein(a) [Lp(a)], apolipoprotein A1 (apoA1), and apolipoprotein B (apoB). Variance components software was used to estimate genetic and environmental influences on serum lipid levels in premenopausal and postmenopausal women. Total variance was higher for triglycerides, HDL, and apoB after menopause. Postmenopausal women showed larger genetic variance for most lipids, apart from apoB and Lp(a). In premenopausal females, total cholesterol, LDL, HDL, apoA1, and apoB all showed an influence of the shared environment (22% to 34%), which, after menopause, decreased in HDL and completely disappeared in total cholesterol, LDL, and apoA1. Only for Lp(a), with a high heritability of 87%, did the same model fit premenopausal and postmenopausal women. Generally, there was no indication that different genes influence lipids before and after menopause. Conclusions — These findings imply that genetic studies of lipids can pool results from premenopausal and postmenopausal women and that family-based interventions, such as changes in diet, are more likely to succeed in younger women, in whom the environmental influences are greater.