Garner C, Tatu T, Reittie J E, Littlewood T, Darley J, Cervino S, Farrall M, Kelly P, Spector T D, Thein S L
Wellcome Trust Centre for Human Genetics, Oxford, UK.
Blood. 2000 Jan 1;95(1):342-6.
To assess the relative contribution of genetic factors in the variation of F cells (FC) and other hematologic variables, we conducted a classical twin study in unselected twins. The sample included 264 identical (monozygotic [MZ]) twin pairs and 511 nonidentical (dizygotic [DZ]) same-sex twin pairs (aged 20 to 80 years) from the St. Thomas' UK Adult Twin Register. The FC values were distributed continuously and positively skewed, with values ranging from 0.6% to 22%. FC values were higher in women than in men and decreased with age, with the variables accounting for 2% of the total FC variance. The intraclass correlations of FC values were higher in MZ (rMZ = 0.89) than in DZ (rDZ = 0.49) twins. The XmnI-(G)gamma polymorphism in the beta-globin gene cluster had a significant effect on FC levels, accounting for approximately 13% of the total FC variance. Variance components analysis showed that the FC values were accounted for predominantly by additive genetic and nonshared environmental influences, with an estimate of heritability of 0.89. Hemoglobin levels and red blood cell, white blood cell, and platelet numbers were also substantially heritable, with heritability estimates of 0.37, 0.42, 0.62, and 0.57, respectively. Previously, studies of sib pairs with sickle cell disease and isolated family studies showed that high levels of Hb F and FC tend to be inherited. Here, our classical twin study demonstrated that the variance of FC levels in healthy adults is largely genetically determined. (Blood. 2000;95:342-346)
为评估遗传因素在F细胞(FC)变异及其他血液学变量中的相对贡献,我们对未经挑选的双胞胎进行了一项经典双胞胎研究。样本包括来自英国圣托马斯成人双胞胎登记处的264对同卵(单卵[MZ])双胞胎和511对非同卵(双卵[DZ])同性双胞胎(年龄在20至80岁之间)。FC值呈连续且正偏态分布,范围为0.6%至22%。女性的FC值高于男性,且随年龄增长而降低,这些变量占FC总方差的2%。MZ双胞胎(rMZ = 0.89)的FC值组内相关性高于DZ双胞胎(rDZ = 0.49)。β-珠蛋白基因簇中的XmnI-(G)γ多态性对FC水平有显著影响,约占FC总方差的13%。方差成分分析表明,FC值主要由加性遗传和非共享环境影响决定,遗传度估计为0.89。血红蛋白水平以及红细胞、白细胞和血小板数量也具有较高的遗传性,遗传度估计分别为0.37、0.42、0.62和0.57。此前,对镰状细胞病同胞对的研究和孤立家系研究表明,高水平的胎儿血红蛋白(Hb F)和FC往往是可遗传的。在此,我们的经典双胞胎研究表明,健康成年人中FC水平的方差在很大程度上是由基因决定的。(《血液》。2000年;95:342 - 346)