Zegers Doreen, Van Hul Wim, Van Gaal Luc F, Beckers Sigri
Department of Medical Genetics, University of Antwerp, Antwerp, Belgium.
Crit Rev Eukaryot Gene Expr. 2012;22(4):325-43. doi: 10.1615/critreveukargeneexpr.v22.i4.60.
The role of genetic factors involved in the etiology of human obesity is beyond question. The identification of the hypothalamic leptin-melanocortin signaling pathway as a critical regulator in energy homeostasis and food intake has been essential for genetic research. In this review, we discuss the involvement of established and novel genes from this pathway in the pathogenesis of obesity. Their roles in monogenic and complex forms of obesity are illustrated by discussing the results of mutation analysis, candidate gene and genome-wide association studies, as well as copy number analysis. While we can conclude from these outcomes that the leptin-melanocortin pathway is of immense importance, there is still a lot of heritability that currently cannot be explained. Future studies implementing genome-wide association studies, genome-wide copy number variant analysis, and whole exome and whole-genome sequencing might aid in finding new variation in the conventional pathways and might reveal new biological pathways implicated in the pathogenesis of obesity.
遗传因素在人类肥胖病因学中的作用毋庸置疑。下丘脑瘦素-黑皮质素信号通路作为能量平衡和食物摄入的关键调节因子被确定，这对遗传学研究至关重要。在本综述中，我们讨论了该通路中已确定的基因和新基因在肥胖发病机制中的作用。通过讨论突变分析、候选基因和全基因组关联研究以及拷贝数分析的结果，阐明了它们在单基因和复杂形式肥胖中的作用。虽然我们可以从这些结果中得出结论，即瘦素-黑皮质素通路非常重要，但目前仍有许多遗传力无法解释。未来开展全基因组关联研究、全基因组拷贝数变异分析以及全外显子组和全基因组测序的研究，可能有助于在传统通路中发现新的变异，并可能揭示肥胖发病机制中涉及的新生物通路。
