Human Genetic Laboratory, Oswaldo Cruz Institute/FIOCRUZ, Rio de Janeiro, Brazil.
Institute of Translational Medicine, Universidad del Rosario, Bogota, Colombia.
J Diabetes Complications. 2017 Oct;31(10):1549-1561. doi: 10.1016/j.jdiacomp.2017.04.026. Epub 2017 Jun 16.
Childhood obesity is a serious public health problem associated with the development of several chronic diseases, such as type 2 diabetes mellitus, dyslipidemia, and hypertension. The elevated prevalence of obesity is mostly due to inadequate diet and lifestyle, but it is also influenced by genetic factors.
To review recent advances in the field of the genetics of obesity. We summarize the list of genes associated with the rare non-syndromic forms of obesity, and explain their function. Furthermore, we discuss the technologies that are available for the genetic diagnosis of obesity.
Several studies reported that single gene variants cause Mendelian forms of obesity, determined by mutations of major effect in single genes. Rare, non-syndromic forms of obesity are a result of loss-of-function mutations in genes that act on the development and function of the hypothalamus or the leptin-melanocortin pathway. These variants disrupt enzymes and receptors that play a role in energy homeostasis, resulting in severe early-onset obesity and endocrine dysfunctions. Different approaches and technologies have been used to understand the genetic background of obesity. Currently, whole genome and whole exome sequencing are important diagnostic tools to identify new genes and variants associated with severe obesity, but other approaches are also useful at individual or population levels, such as linkage analysis, candidate gene sequencing, chromosomal microarray analysis, and genome-wide association studies.
The understanding of the genetic causes of obesity and the usefulness and limitations of the genetic diagnostic approaches can contribute to the development of new personalized therapeutic targets against obesity.
儿童肥胖是一个严重的公共卫生问题，与多种慢性疾病的发生有关，如 2 型糖尿病、血脂异常和高血压。肥胖症的高发主要是由于饮食和生活方式不当，但也受到遗传因素的影响。
综述肥胖遗传学领域的最新进展。我们总结了与罕见非综合征性肥胖相关的基因列表，并解释了它们的功能。此外，我们还讨论了用于肥胖症遗传诊断的技术。
几项研究表明，单基因突变导致孟德尔肥胖形式，由单个基因中的主要效应突变决定。罕见的非综合征性肥胖是由于下丘脑或瘦素-黑素皮质素途径相关基因的功能丧失性突变引起的。这些变异会破坏在能量平衡中发挥作用的酶和受体，导致严重的早发性肥胖和内分泌功能障碍。已经使用了不同的方法和技术来了解肥胖的遗传背景。目前，全基因组和全外显子组测序是识别与严重肥胖相关的新基因和变异的重要诊断工具，但其他方法在个体或群体水平上也很有用，如连锁分析、候选基因测序、染色体微阵列分析和全基因组关联研究。
了解肥胖的遗传原因以及遗传诊断方法的实用性和局限性有助于开发针对肥胖的新的个性化治疗靶点。
