Dunger D B, Petry C J, Ong K K
Department of Paediatrics, University of Cambridge, Addenbrooke's Hospital, UK.
Horm Res. 2006;65 Suppl 3:34-40. doi: 10.1159/000091504. Epub 2006 Apr 10.
Size at birth is said to be a highly heritable trait, with an estimated 30-70% of the variability a result of genetics. Data from family studies may be confounded, however, by potential interactions between fetal genes and the maternal uterine environment. Overall, the maternal environment tends to restrain fetal growth, and this is most evident in first pregnancies. Restraint of fetal growth appears to be inherited through the maternal line. Potential genetic candidates include the mitochondrial DNA 16189 variant, and common variants of exclusively maternally expressed genes, such as H19, which have been associated with size at birth. Maternal blood glucose levels and blood pressure are also correlated with size at birth, but the degree to which these changes relate to genetic variation in the mother is unclear. Elegant studies in mouse knockout models and rare genetic variants in humans have highlighted the importance of insulin-like growth factor I (IGF-I), IGF-II, insulin and their respective receptors in determining fetal growth. However, data linking common variation in the genes that regulate these proteins and receptors with size at birth are few and inconsistent. Interestingly, common variation in the insulin gene (INS) variable number tandem repeats, which regulates the transcription of insulin and IGF-II, has been associated with size at birth, largely in second and subsequent pregnancies, where maternal restraint is least evident. This suggests that fetal genes, and in particular paternally expressed genes, may have significant effects on fetal growth during pregnancies where maternal restraint of fetal growth is less evident.
出生时的体型据说是一种高度可遗传的特征，估计30%-70%的变异性是由基因决定的。然而，家族研究的数据可能会因胎儿基因与母体子宫环境之间的潜在相互作用而产生混淆。总体而言，母体环境往往会抑制胎儿生长，这在初产时最为明显。胎儿生长受限似乎是通过母系遗传的。潜在的基因候选包括线粒体DNA 16189变体，以及仅由母体表达的基因（如H19）的常见变体，这些基因与出生时的体型有关。母体血糖水平和血压也与出生时的体型相关，但这些变化与母亲基因变异的关联程度尚不清楚。对小鼠基因敲除模型的精细研究以及人类中的罕见基因变体突出了胰岛素样生长因子I（IGF-I）、IGF-II、胰岛素及其各自受体在决定胎儿生长中的重要性。然而，将调节这些蛋白质和受体的基因的常见变异与出生时的体型联系起来的数据很少且不一致。有趣的是，调节胰岛素和IGF-II转录的胰岛素基因（INS）可变数目串联重复序列的常见变异与出生时的体型有关，主要在二胎及后续妊娠中，此时母体抑制作用最不明显。这表明胎儿基因，尤其是父系表达的基因，可能在母体对胎儿生长抑制作用不明显的妊娠期间对胎儿生长有显著影响。
