Rodriguez Santiago, Gaunt Tom R, Day Ian N M
Bristol Genetic Epidemiology Laboratories and MRC Centre for Causal Analyses in Translational Epidemiology (CAiTE), Department of Social Medicine, University of Bristol, Canynge Hall, Whiteladies Road, Bristol, BS8 2PR, UK.
Hum Genet. 2007 Aug;122(1):1-21. doi: 10.1007/s00439-007-0378-3. Epub 2007 May 30.
The human growth hormone gene (GH1) and the insulin-like growth factor 1 and 2 genes (IGF1 and IGF2) encode the central elements of a key pathway influencing growth in humans. This "growth pathway" also includes transcription factors, agonists, antagonists, receptors, binding proteins, and endocrine factors that constitute an intrincate network of feedback loops. GH1 is evolutionarily coupled with other genes in linkage disequilibrium in 17q24.2, and the same applies to IGF2 in 11p15.5. In contrast, IGF1 in 12q22-24.1 is not in strong linkage disequilibrium with neighbouring genes. Knowledge of the functional architecture of these regions is important for the understanding of the combined evolution and function of GH1, IGF2 and IGF1 in relation to complex diseases. A number of mutations accounting for rare Mendelian disorders have been described in GH-IGF elements. The constellation of genes in this key pathway contains potential candidates in a number of complex diseases, including growth disorders, metabolic syndrome, diabetes (notably IGF2BP2) cardiovascular disease, and central nervous system diseases, and in longevity, aging and cancer. We review these genes and their associations with disease phenotypes, with special attention to metabolic risk traits.
人类生长激素基因（GH1）以及胰岛素样生长因子1和2基因（IGF1和IGF2）编码了影响人类生长的关键途径的核心要素。这条“生长途径”还包括转录因子、激动剂、拮抗剂、受体、结合蛋白和内分泌因子，它们构成了一个错综复杂的反馈回路网络。GH1在进化上与17q24.2中处于连锁不平衡状态的其他基因相关联，11p15.5中的IGF2也是如此。相比之下，12q22 - 24.1中的IGF1与相邻基因不存在强连锁不平衡。了解这些区域的功能结构对于理解GH1、IGF2和IGF1在复杂疾病中的联合进化和功能非常重要。在GH - IGF元件中已经描述了一些导致罕见孟德尔疾病的突变。这条关键途径中的基因组合包含了许多复杂疾病的潜在候选基因，包括生长障碍、代谢综合征、糖尿病（特别是IGF2BP2）、心血管疾病和中枢神经系统疾病，以及长寿、衰老和癌症。我们综述这些基因及其与疾病表型的关联，特别关注代谢风险特征。
