Genetic and Environmental Influences on Lipids, Lipoproteins, and Apolipoproteins

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. Key Words: lipids Ⅲ genetics Ⅲ twin study Ⅲ menopause P ostmenopausal women are 2 to 3 times more likely to suffer from coronary heart disease than are premenopausal women. 1,2 Part of this increased risk is likely to be due to adverse changes in lipids and (apo)lipoproteins after menopause. Levels of total cholesterol, LDL, triglycerides, and apoB have been reported to increase, 3,4 probably (at least partly) because of a reduction in LDL receptor activity in response to the gradual decline in blood estrogen levels in the perimenopausal years. 5,6 Levels of lipids, lipoproteins, and apolipoproteins, which have been established as important predictors of atherosclerotic coronary disease, 7 vary considerably over a lifespan, and their phenotypic variance generally shows an increase with age. 8 -11 Such an increase in lipid and (apo)lipoprotein variance may be due to interindividual variation in the rise of lipid levels over time, and several studies now indicate that different genetic and/or environmental factors are likely to be involved at different ages. 10,12,13 Superimposed on the global change across the whole lifespan, 4 specific time periods are associated with more dramatic changes. Menopause is one of these; the others are old age, adolescence, and the first years after birth. Conclusions-TheseWe recently reviewed twin studies of lipids and (apo)lipoproteins and showed that most studies report heritability (h 2 ) estimates between 40% and 80% for total cholesterol, LDL, HDL, triglycerides, apoA1, and apoB, with Lp(a) h 2 values of Ϸ90%. 11 Only one study, which reported on HDL alone, focused on the effect of menopause and found that postmenopausal m...

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