Rahman Iffat, Bennet Anna M, Pedersen Nancy L, de Faire Ulf, Svensson Per, Magnusson Patrik K E
1 Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
Twin Res Hum Genet. 2009 Jun;12(3):286-94. doi: 10.1375/twin.12.3.286.
In twin studies of cardiovascular disease biomarkers the dizygotic correlations are often estimated to be less than half of monozygotic correlations indicating a potential influence of nonadditive genetic factors. Using a large and homogenous sample, we estimated the additive and dominance genetic influences on levels of high density lipoprotein, low density lipoprotein, apolipoprotein A-I, apolipoprotein B, total cholesterol, triglycerides, glucose, hemoglobin Alc and c-reactive protein, all of which are biomarkers associated with cardiovascular disease. The blood biomarkers were measured on 12,000 Swedish twins born between 1911 and 1958. The large sample allowed us to obtain heritability estimates with considerable precision and provided adequate statistical power for estimation of dominance genetic components. Our study showed complete absence of the shared environment component for the investigated traits. Dominant genetic component was shown to be significant for low density lipoprotein (0.18), glucose (0.31), Hemoglobin Alc (0.55), and c-reactive protein (0.27). To our knowledge, this is the first statistically significant evidence for dominance genetic variance found for low density lipoprotein, glucose, hemoglobin Alc, and c-reactive protein in a population based twin sample. The study highlights the importance of acknowledging nonadditive genes underlying the risk of developing cardiovascular diseases.
在心血管疾病生物标志物的双胞胎研究中，异卵双胞胎的相关性估计通常不到同卵双胞胎相关性的一半，这表明非加性遗传因素可能产生影响。我们使用一个大型同质样本，估计了加性和显性遗传因素对高密度脂蛋白、低密度脂蛋白、载脂蛋白A-I、载脂蛋白B、总胆固醇、甘油三酯、葡萄糖、糖化血红蛋白和C反应蛋白水平的影响，所有这些都是与心血管疾病相关的生物标志物。对1911年至1958年间出生的12000名瑞典双胞胎进行了血液生物标志物检测。这个大样本使我们能够相当精确地获得遗传力估计值，并为估计显性遗传成分提供了足够的统计效力。我们的研究表明，所研究的性状完全不存在共享环境成分。显性遗传成分对低密度脂蛋白（0.18）、葡萄糖（0.31）、糖化血红蛋白（0.55）和C反应蛋白（0.27）具有显著意义。据我们所知，这是在基于人群的双胞胎样本中首次发现低密度脂蛋白、葡萄糖、糖化血红蛋白和C反应蛋白存在显性遗传变异的统计学显著证据。该研究强调了认识到心血管疾病发生风险背后的非加性基因的重要性。
