Middelberg Rita P S, Spector Tim D, Swaminathan Ramasamyiyer, Snieder Harold
Twin Research and Genetic Epidemiology Unit, St. Thomas' Hospital, London, UK.
Arterioscler Thromb Vasc Biol. 2002 Jul 1;22(7):1142-7. doi: 10.1161/01.atv.0000022889.85440.79.
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.
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.
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.
已知绝经后血脂和(载)脂蛋白水平会升高,但遗传和环境变异性是否会改变,以及绝经前后血脂和(载)脂蛋白是否受不同基因影响尚不清楚。
我们对从英国圣托马斯成人双胞胎登记处招募的453对单卵和1280对双卵女性白人双胞胎进行了研究,测量了总胆固醇、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)、甘油三酯、脂蛋白(a) [Lp(a)]、载脂蛋白A1(apoA1)和载脂蛋白B(apoB)。使用方差成分软件估计绝经前和绝经后女性血清脂质水平的遗传和环境影响。绝经后甘油三酯、HDL和apoB的总方差更高。除apoB和Lp(a)外,绝经后女性大多数脂质的遗传方差更大。在绝经前女性中,总胆固醇、LDL、HDL、apoA1和apoB均显示出共同环境的影响(22%至34%),绝经后,HDL的这种影响降低,总胆固醇、LDL和apoA1的这种影响完全消失。只有Lp(a)的遗传度高达87%,相同模型适用于绝经前和绝经后女性。一般来说,没有迹象表明绝经前后不同基因影响脂质。
这些发现表明,脂质的遗传研究可以汇总绝经前和绝经后女性的结果,而且基于家庭的干预措施,如饮食改变,在环境影响更大的年轻女性中更有可能成功。