中国实用儿科杂志

中国实用儿科杂志 ›› 2024, Vol. 39 ›› Issue (12): 941-948.DOI: 10.19538/j.ek2024120611

• 论著 • 上一篇    下一篇

基于全外显子测序技术对儿童肥胖症的遗传病因及临床表型研究

  

  1. 1 .江西省儿童医院  a 江西省儿童发育与遗传重点实验室，b 内分泌遗传代谢科，江西  南昌  330006；2.江西省儿童遗传代谢性疾病临床医学研究中心，江西  南昌  330006
  • 出版日期:2024-12-06 发布日期:2025-02-24
  • 通讯作者: 杨玉，电子信箱：yangyu5168@126.com
  • 基金资助:
    儿童发育江西省重点实验室项目（2024SSY06191）；儿童疑难罕见病早期筛查新技术及其应用研究项目（2023ZD007）

A study on the genetic etiology and clinical phenotypes of childhood obesity based on whole exome sequencing technology

  1. *Jiangxi Provincial Key Laboratory of Child Development and Genetics，Jiangxi Provincial Children's Hospital，Nanchang  330006，China
  • Online:2024-12-06 Published:2025-02-24

摘要： 目的　探讨非综合征型儿童青少年肥胖症的遗传学病因及临床表型。方法　收集2020年1月至2022年6月在江西省儿童医院内分泌遗传代谢科就诊住院的7～14岁非综合征型肥胖症患儿共计391例。采用全外显子测序筛查潜在的遗传学病因并对含肥胖目标基因基因拷贝数变异（CNV）及79个已报道的肥胖症候选基因进一步分析，采用美国医学遗传学与基因组学学会（ACMG）指南对变异评级，并对基因变异及临床表型进行分析。结果　共计纳入391例非综合征型儿童青少年肥胖症患儿，均在10岁以下出现肥胖症状，男童302例和女童90例，男女比为3.38∶1；肥胖基因筛查结果：筛查出32例（32/391，8.2%）患儿携带18个非综合征型肥胖基因，阳性组患儿男女比为2.2∶1，年龄分布以9～12岁最为常见。其中，UCP3基因和MC4R基因最为常见；临床表型与遗传学相关性分析：经单因素分析和多因素Logistics回归分析发现，患儿的尿微量蛋白、游离T4（FrT4）、血清丙氨酸转移酶（ALT）、血清谷氨酰转肽酶（OGG）、尿酸、血磷、父亲体重、糖尿病、肥胖或高血压家族史、糖耐量受损（IGT）、非高密度脂蛋白胆固醇（non-HDL-C）、合并代谢综合征等项差异有明显统计学意义（P<0.05）；多因素Logistics统计分析显示血磷是儿童青少年肥胖症遗传因素的独立危险因素（P<0.05）。结论　研究发现儿童青少年非综合征型肥胖症患儿中，UCP3、MC4R基因为非综合征型肥胖症最常见的基因，可能为非综合征型肥胖热点基因；根据单因素分析结果构建并验证了列线图预测模型，为遗传高风险患儿临床筛查提供了临床风险预测指标。

关键词: 儿童, 青少年, 肥胖症, 遗传风险

Abstract: Objective    To explore the genetic etiology and clinical phenotypes of non-syndromic obesity in children and adolescents. Methods    We collected the data of 391 non-syndromic obese children aged 7-14 years，who were admitted to the Department of Endocrinology，Genetics and Metabolism of Jiangxi Children's Hospital from January 2020 to June 2022. Whole-exome sequencing was employed to identify potential genetic causes，followed by a detailed analysis of copy number variations （CNVs），obesity-associated target genes，and 79 previously reported candidate genes for obesity. The American College of Medical Genetics and Genomics （ACMG） guidelines were utilized to classify genetic variants and to analyze gene variations and clinical phenotypes. Results    The study cohort comprised 391 non-syndromic obese children and adolescents，all of whom exhibited obesity symptoms before the age of 10，with 302 males and 90 females，resulting in a male-to-female ratio of 3.38∶1. Genetic screening outcomes： A total of 32 cases （8.2%） were identified carrying 18 non-syndromic obesity genes，with a male-to-female ratio of 2.2∶1 in the positive group. The majority of these cases were observed in the 9-12-year-old age bracket，with UCP3 and MC4R being the most common genes. Clinical-genetic correlations： Univariate and multivariate logistic regression analyses revealed that there were significant statistical differences in urinary trace proteins，free thyroxine （fT4），serum alanine aminotransferase （ALT），serum glutamyl transpeptidase （GGT），uric acid，blood phosphorus，paternal weight，family history of diabetes，obesity and hypertension， impaired glucose tolerance （IGT）， non-high-density lipoprotein cholesterol（non-HDL-C）， and complicated metabolic syndrome （P<0.05）. Multivariate Logistics statistical analysis showed that blood phosphorus emerged as an independent risk factor for genetic factors of obesity in children and adolescents （P<0.05）. Conclusion    This study has identified UCP3 and MC4R as the most prevalent genes associated with non-syndromic obesity in children and adolescents，suggesting their potential as key genetic markers. Based on univariate analysis，a nomogram prediction model is developed and validated to serve as a clinical tool for risk prediction and to guide the screening of genetically susceptible children.

Key words: child, adolescents, obesity, genetic risk