Zuccaro Michael V, LeDuc Charles A, Thaker Vidhu V
Division of Genetics and Genomics, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA, 02115, United States.
Division of Molecular Genetics, Department of Pediatrics, Columbia University Irving Medical Center, 1150, St. Nicholas Avenue, NY 10032, United States.
Curr Obes Rep. 2024 Sep;13(3):626-641. doi: 10.1007/s13679-024-00567-y. Epub 2024 Jun 1.
The goal of this paper is to aggregate information on monogenic contributions to obesity in the past five years and to provide guidance for genetic testing in clinical care.
Advances in sequencing technologies, increasing awareness, access to testing, and new treatments have increased the utilization of genetics in clinical care. There is increasing recognition of the prevalence of rare genetic obesity from variants with mean allele frequency < 5% -new variants in known genes as well as identification of novel genes- causing monogenic obesity. While most of these genes are in the leptin melanocortin pathway, those in adipocytes may also contribute. Common variants may contribute either to higher lifetime tendency for weight gain or provide protection from monogenic obesity. While specific genetic mutations are rare, these segregate in individuals with early-onset severe obesity; thus, collectively genetic etiologies are not as rare. Some genetic conditions are amenable to targeted treatment. Research into the discovery of novel genetic causes as well as targeted treatment is growing over time. The utility of therapeutic strategies based on the genetic risk of obesity is an advancing frontier.
本文旨在汇总过去五年中关于单基因对肥胖影响的信息，并为临床护理中的基因检测提供指导。
测序技术的进步、意识的提高、检测的可及性以及新疗法增加了遗传学在临床护理中的应用。人们越来越认识到罕见基因性肥胖的患病率，这些肥胖由平均等位基因频率<5%的变异引起——已知基因中的新变异以及新基因的鉴定——导致单基因肥胖。虽然这些基因大多处于瘦素-促黑素细胞激素途径，但脂肪细胞中的基因也可能起作用。常见变异可能导致更高的终生体重增加倾向，或提供对单基因肥胖的保护。虽然特定基因突变很少见，但它们在早发性严重肥胖个体中呈分离状态；因此，总体而言，遗传病因并不罕见。一些遗传疾病适合进行靶向治疗。随着时间的推移，对新型遗传病因的发现以及靶向治疗的研究不断增加。基于肥胖遗传风险的治疗策略的效用是一个不断发展的前沿领域。
