Austin M A, Sandholzer C, Selby J V, Newman B, Krauss R M, Utermann G
Department of Epidemiology, School of Public Health and Community Medicine, University of Washington, Seattle 98195.
Am J Hum Genet. 1992 Oct;51(4):829-40.
Lp(a) is a unique lipoprotein consisting of an LDL-like particle and a characteristic protein, apo(a). Increased levels of Lp(a) constitute a risk factor for coronary heart disease. Variation in the size of the apo(a) protein is a phenotype controlled by the apo(a) gene on chromosome 6 and is related to Lp(a) plasma levels. Based on 169 MZ and 125 DZ adult female twin pairs, this study's purpose was to estimate the proportion of the variation in Lp(a) levels that is due to genetic influences and to determine the extent to which the apo(a) locus explains this heritability. Lp(a) levels were significantly more similar in MZ twins than in DZ twins: mean co-twin differences were 3.9 +/- 5.7 mg/dl and 16.0 +/- 19.9 mg/dl (P less than .001), respectively. Intraclass correlations were .94 in MZ twins and .32 in DZ twins, resulting in a heritability estimate of .94 (P less than .001). Heritability was then calculated using only co-twins with the same apo(a) phenotype: the heritability estimate decreased to .45 but was still highly significant (P less than .001). Therefore, on the basis of heritability analysis of women twins, Lp(a) levels are almost entirely genetically controlled. Variation at the apo(a) locus contributes to this heritability, although other genetic factors could be involved.
脂蛋白(a)[Lp(a)]是一种独特的脂蛋白,由一个低密度脂蛋白(LDL)样颗粒和一种特征性蛋白质载脂蛋白(a)[apo(a)]组成。Lp(a)水平升高是冠心病的一个危险因素。apo(a)蛋白大小的变异是一种由6号染色体上的apo(a)基因控制的表型,并且与Lp(a)血浆水平相关。基于169对同卵(MZ)成年女性双胞胎和125对异卵(DZ)成年女性双胞胎,本研究的目的是估计Lp(a)水平变异中由遗传影响所致的比例,并确定apo(a)基因座对这种遗传度的解释程度。MZ双胞胎的Lp(a)水平比DZ双胞胎的显著更相似:平均双胞胎间差异分别为3.9±5.7mg/dl和16.0±19.9mg/dl(P<0.001)。组内相关系数在MZ双胞胎中为0.94,在DZ双胞胎中为0.32,得出遗传度估计值为0.94(P<0.001)。然后仅使用具有相同apo(a)表型的双胞胎计算遗传度:遗传度估计值降至0.45,但仍高度显著(P<0.001)。因此,基于对女性双胞胎的遗传度分析,Lp(a)水平几乎完全由基因控制。apo(a)基因座的变异促成了这种遗传度,尽管可能涉及其他遗传因素。