Premawardhana L D, Lo S S, Phillips D I, Prentice L M, Rees Smith B
Department of Medicine, University of Wales College of Medicine, Cardiff, UK.
Clin Endocrinol (Oxf). 1994 Dec;41(6):725-9. doi: 10.1111/j.1365-2265.1994.tb02786.x.
There are large variations in the circulating concentrations of thyroglobulin. The purpose of this study was to explore the possibility of a genetic basis for the variability of serum concentration of thyroglobulin (Tg) in euthyroid individuals.
The serum concentration of thyroglobulin (Tg) varies several-fold in euthyroid individuals. Other circulating proteins also show wide normal ranges of concentration and these variations have been shown to have a genetic as well as an environmental basis. To explore the possibility of a genetic basis for variability in serum Tg levels, an analysis was made of serum Tg levels in 44 pairs of identical twins and 66 nuclear families who were euthyroid and thyroid autoantibody negative (thereby eliminating subclinical autoimmune thyroid disease and Tg autoantibody interference with the Tg assay).
Each pair of identical twins tended to have a similar Tg level and the overall correlation was highly significant (r = 0.734, P < 0.001). There was no relation between Tg and TSH levels in the twins (r = 0.119; P = 0.366). Segregation analysis of the 66 families showed that where both parents had Tg levels above the overall median for the subjects (males, 19 micrograms/l; females, 33 micrograms/l), 73% of the offspring also had concentrations above these levels, compared with 30% of the offspring when one parent had a high Tg level and only 16% in families where neither parent had a high Tg level.
Complex segregation analysis using the computer program Pointer suggested that variability in Tg levels was the result of a major dominant-like gene effect (accounting for 80% of the variability) combined with a multifactorial component. Thyroglobulin, a template for thyroid hormone production, is also a major thyroid autoantigen and inherited variations in serum Tg levels may have implications for the pathogenesis of autoimmune thyroid disease.
甲状腺球蛋白的循环浓度存在很大差异。本研究的目的是探讨甲状腺功能正常个体血清甲状腺球蛋白（Tg）浓度变异性的遗传基础的可能性。
甲状腺功能正常个体的血清甲状腺球蛋白（Tg）浓度变化数倍。其他循环蛋白也显示出广泛的正常浓度范围，并且这些变化已被证明具有遗传和环境基础。为了探讨血清Tg水平变异性的遗传基础的可能性，对44对同卵双胞胎和66个核心家庭的血清Tg水平进行了分析，这些家庭甲状腺功能正常且甲状腺自身抗体阴性（从而消除亚临床自身免疫性甲状腺疾病和Tg自身抗体对Tg测定的干扰）。
每对同卵双胞胎的Tg水平往往相似，总体相关性非常显著（r = 0.734，P < 0.001）。双胞胎中Tg与TSH水平之间无相关性（r = 0.119；P = 0.366）。对66个家庭的分离分析表明，父母双方的Tg水平均高于受试者的总体中位数（男性，19微克/升；女性，33微克/升）时，73%的后代的浓度也高于这些水平，而当一方父母的Tg水平高时，后代中这一比例为30%，父母双方均无高Tg水平的家庭中这一比例仅为16%。
使用计算机程序Pointer进行的复杂分离分析表明，Tg水平的变异性是主要的显性样基因效应（占变异性的80%）与多因素成分共同作用的结果。甲状腺球蛋白是甲状腺激素产生的模板，也是主要的甲状腺自身抗原，血清Tg水平的遗传变异可能对自身免疫性甲状腺疾病的发病机制有影响。
