单基因非综合征肥胖的遗传研究进展  

Advances in Genetic Research of Monogenic Non-syndromic Obesity

作　　者：李颖 刘彦山 石磊[1] 张学 Li Ying;Liu Yanshan;Shi Lei;Zhang Xue(Key Laboratory of National Health Commission,the Fourth Affiliated Hospital of Harbin Medical University,Harbin 150028,China;Pediatric laboratory,Wuxi Children’s Hospital Affiliated to Nanjing Medical University,Wuxi 214023,China)

机构地区：[1]哈尔滨医科大学附属第四医院国家卫健委重点实验室,150028 [2]南京医科大学附属无锡市儿童医院儿科实验室,214023

出　　处：《国际遗传学杂志》2021年第6期444-451,共8页International Journal of Genetics

基　　金：国家卫健委重点实验室专项经费(2019PT310001)。

摘　　要：肥胖是一种复杂代谢性疾病, 由能量摄入与消耗不平衡, 脂肪过度积累导致, 其发病率逐年上升, 已经成为全球性的流行病。肥胖具有多病因性, 遗传、表观遗传、环境因素及其之间的相互作用均能影响肥胖的病理进程。单基因非综合征肥胖(monogenic non-syndromic obesity)是一种特殊类型的肥胖, 临床一般表现为严重食欲亢进和早发性肥胖, 通常由瘦素-黑素皮质素通路(leptin-melanocortin pathway)的单基因突变导致。信号素3(semaphorin 3, SEMA3)通路的基因突变也被证实导致单基因非综合征肥胖。随着测序技术的发展, 其他肥胖致病基因被相继鉴定。基于单基因非综合征肥胖的致病基因已经开发出一些靶向治疗药物, 如重组人瘦素和黑皮质素4受体激动剂。本文就单基因非综合征肥胖的遗传学研究作一综述。Obesity is a complex disease characterized by the imbalance of energy intake and expenditure,followed by the excessive accumulation of body fat.Obesity is now a global epidemic with the increasing incidence over recent years.The multifactorial etiology of obesity implies that the combination effect of genetic variations,epigenetic modifications,environmental influences,and their interactions on its pathogenesis.Specially,the patients with monogenic non-syndromic obesity usually exhibit early-onset excess fat and severe hyperphagia,and harbor the monogenic mutations of the leptin-melanocortin or semaphorin 3(SEMA3)pathway.More obesity-causing genes or genetic variants have been rapidly and successively identified in the era of high-throughput sequencing.The research and development of targeted-drug based on genetic discoveries has achieved preliminary results,such as recombinant human leptin and MC4R agonists.This review summarizes the advanced genetic research of the monogenic non-syndromic obesity.

关 键 词：单基因肥胖 突变 瘦素-黑素皮质素通路 信号素3通路 

分 类 号：R589.2[医药卫生—内分泌]