Exploration of New Susceptible Genes associated with Non-Alcoholic Fatty Liver Disease among Children with Obesity Using Whole Exome Sequencing.

Xiong Feng PAN; Cai Lian WEI; Jia You LUO; Jun Xia YAN; Xiang XIAO; Jie WANG; Yan ZHONG; Mi Yang LUO

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Exploration of New Susceptible Genes associated with Non-Alcoholic Fatty Liver Disease among Children with Obesity Using Whole Exome Sequencing.

Author: Xiong Feng PAN ¹ ; Cai Lian WEI ² ; Jia You LUO ³ ; Jun Xia YAN ² ; Xiang XIAO ³ ; Jie WANG ⁴ ; Yan ZHONG ⁵ ; Mi Yang LUO ²
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1. Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha 410008, Hunan, China;Pediatrics Research Institute of Hunan Province, Hunan Children's Hospital, The Affiliated Children's Hospital of Xiangya School of Medicine, Central South University, Changsha 410008, Hunan, China;The School of Pediatrics, Hunan Provincial Key Laboratory of Pediatric Orthopedics, The school of pediatrics, University of South China, Changsha 410008, Hunan, China.
2. Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha 410008, Hunan, China.
3. Department of Child and Adolescent Health and Maternal and Child Health, Xiangya School of Public Health, Central South University, Changsha 410008, Hunan, China.
4. Supervision and Inspection Department of Shanghai Healthcare Security Bureau, Shanghai 200003, China.
5. Children's Health Center, Hunan Children's Hospital, Changsha 410008, Hunan, China.
Publication Type:Journal Article
Keywords: Interaction; Non-alcoholic fatty liver disease; Obese children; Single nucleotide polymorphism; Susceptible genes; Whole-exome sequencing
MeSH: Humans; Non-alcoholic Fatty Liver Disease/genetics*; Child; Male; Female; Genetic Predisposition to Disease; Case-Control Studies; Exome Sequencing; Adolescent; Polymorphism, Single Nucleotide; Obesity/complications*; Pediatric Obesity/complications*; China
From: Biomedical and Environmental Sciences 2025;38(6):727-739
CountryChina
Language:English
Abstract: OBJECTIVE:This study aimed to evaluate the association between susceptibility genes and non-alcoholic fatty liver disease (NAFLD) in children with obesity.
METHODS:We conducted a two-step case-control study. Ninety-three participants were subjected to whole-exome sequencing (exploratory set). Differential genes identified in the small sample were validated in 1,022 participants using multiplex polymerase chain reaction and high-throughput sequencing (validation set).
RESULTS:In the exploratory set, 14 genes from the NAFLD-associated pathways were identified. In the validation set, after adjusting for sex, age, and body mass index, ECI2 rs2326408 (dominant model: OR = 1.33, 95% CI: 1.02-1.72; additive model: OR = 1.22, 95% CI: 1.01-1.47), C6orf201 rs659305 (dominant model: OR = 1.30, 95% CI: 1.01-1.69; additive model: OR = 1.21, 95% CI: 1.00-1.45), CALML5 rs10904516 (pre-ad dominant model: OR = 1.36, 95% CI: 1.01-1.83; adjusted dominant model: OR = 1.40, 95% CI: 1.03-1.91; and pre-ad additive model: OR = 1.26, 95% CI: 1.04-1.66) polymorphisms were significantly associated with NAFLD in children with obesity ( P < 0.05). Interaction analysis revealed that the gene-gene interaction model of CALML5 rs10904516, COX11 rs17209882, and SCD5 rs3733228 was optional ( P < 0.05), demonstrating a negative interaction between the three genes.
CONCLUSION:In the Chinese population, the CALML5 rs10904516, C6orf201 rs659305, and ECI2 rs2326408 variants could be genetic markers for NAFLD susceptibility.