[Associations of candidate gene polymorphisms, gut microbiota, and their interactions with NAFLD in obese children].

Authors

Cailian Wei, Xiongfeng Pan, Yaoxing Liu, Zhihang Huang, Jia Wei, Jiayou Luo, Miyang Luo

Published in

Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences. Volume 51. Issue 5. Pages 937-946. May 28, 2026.

Abstract

The prevalence of non-alcoholic fatty liver disease (NAFLD) in obese children has been increasing year by year. Its pathogenesis involves the joint effects of genes and gut microbiota, but their interaction effects remain unclear. This study aims to investigate the associations of gene polymorphisms, gut microbiota, and their interactions with NAFLD in obese children, thereby providing new clues for research on the pathogenesis of NAFLD in this population.
A case-control study was conducted. A total of 87 obese children with NAFLD who visited Hunan Children's Hospital from January 2020 to September 2021 were selected as a case group, and 50 obese children without NAFLD who visited the hospital during the same period were selected as a control group. Polymorphisms in 52 candidate genes were detected using multiplex polymerase chain reaction and high-throughput sequencing, and the composition of the gut microbiota was analyzed using 16S ribosomal DNA (16S rDNA) sequencing. Logistic regression was used to analyze the associations between candidate gene polymorphisms and NAFLD in obese children, and the Benjamini-Hochberg method was applied for false discovery rate (FDR) correction in multiple comparisons, with an expected FDR of 0.05. Linear discriminant analysis effect size (LEfSe) analysis was used to compare the relative abundance of gut microbiota at the genus level. Logistic regression models, crossover analysis, and generalized multifactor dimensionality reduction (GMDR) were used to explore two-factor gene-microbiota interactions and the associations of higher-order multifactor interactions with the risk of NAFLD in obese children.
After adjustment for sex, age, and body mass index, PRKAB1 rs6490265 and IL32 rs28372698 were both significantly associated with NAFLD in obese children (both P<0.05). IL32 rs28372698 remained statistically significant after FDR correction, under both the dominant and additive models (P_adj=0.035), whereas PRKAB1 rs6490265 showed no significant differences in any model after FDR correction. Compared with the control group, Escherichia-Shigella, Enterobacter, Bacteroides, Klebsiella, Dialister, and Erysipelotrichaceae_UCG_003 were significantly enriched in the NAFLD group (all P<0.05). Compared with the NAFLD group, Intestinibacter, Coprococcus, Ralstonia, Ligilactobacillus, Fusicatenibacter, Sarcina, Eubacterium_eligens_group, and Pseudomonas were significantly enriched in the control group (all P<0.05). Multiplicative interaction analysis showed that the interaction terms between PRKAB1 rs6490265 and Bacteroides, between PRKAB1 rs6490265 and Intestinibacter, and between IL32 rs28372698 and Ligilactobacillus were statistically significant (all P<0.05). GMDR higher-order interaction analysis showed that the interaction among IL32 rs28372698, Ligilactobacillus, and Intestinibacter was the best model.
Polymorphisms in PRKAB1 and IL32 may be potentially associated with the risk of NAFLD in obese children. The antagonistic interaction effects between PRKAB1 rs6490265 and the abundance of Bacteroides and Enterobacter, as well as the synergistic interaction effect between IL32 rs28372698 and the abundance of Ligilactobacillus, may jointly influence the risk of NAFLD in obese children.

PMID:
42565570
Bibliographic data and abstract were imported from PubMed on 07 Aug 2026.

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