Association between polymorphisms in the glucose metabolism and lipid regulation genes with metabolic abnormalities in childhood obesity

XIA Zhiwei; GONG Zhaolong; LIU Tingting; WANG Lu; ZHAO Hai; SUN Bingjie; LI Yan; YIN Jiyong; HUO Junsheng

doi:10.16835/j.cnki.1000-9817.2025172

Volume 46 Issue 6

Jun. 2025

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XIA Zhiwei, GONG Zhaolong, LIU Tingting, WANG Lu, ZHAO Hai, SUN Bingjie, LI Yan, YIN Jiyong, HUO Junsheng. Association between polymorphisms in the glucose metabolism and lipid regulation genes with metabolic abnormalities in childhood obesity[J]. CHINESE JOURNAL OF SCHOOL HEALTH, 2025, 46(6): 888-893. doi: 10.16835/j.cnki.1000-9817.2025172

Citation:

XIA Zhiwei, GONG Zhaolong, LIU Tingting, WANG Lu, ZHAO Hai, SUN Bingjie, LI Yan, YIN Jiyong, HUO Junsheng. Association between polymorphisms in the glucose metabolism and lipid regulation genes with metabolic abnormalities in childhood obesity[J]. CHINESE JOURNAL OF SCHOOL HEALTH, 2025, 46(6): 888-893. doi: 10.16835/j.cnki.1000-9817.2025172

Citation:

XIA Zhiwei, GONG Zhaolong, LIU Tingting, WANG Lu, ZHAO Hai, SUN Bingjie, LI Yan, YIN Jiyong, HUO Junsheng. Association between polymorphisms in the glucose metabolism and lipid regulation genes with metabolic abnormalities in childhood obesity[J]. CHINESE JOURNAL OF SCHOOL HEALTH, 2025, 46(6): 888-893. doi: 10.16835/j.cnki.1000-9817.2025172

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Association between polymorphisms in the glucose metabolism and lipid regulation genes with metabolic abnormalities in childhood obesity

doi: 10.16835/j.cnki.1000-9817.2025172

1.
Institute of Nutrition and Health, Chinese Center for Disease Control and Prevention/NHC Key Laboratory of Public Nutrition and Health, Beijing(100050), China

Received Date: 2025-05-07
Rev Recd Date: 2025-05-21

Available Online: 2025-07-04

Publish Date: 2025-06-25

Abstract

Abstract

Objective To explore the association between CDKAL1 rs35261542, FAIM2 rs3205718, and VGLL4 rs2574704 polymorphisms with childhood obesity and related metabolic phenotypes to provide evidence for personalized prevention and management strategies. Methods Based on the 2023 Long-term Nutritional Health Effects of Early Childhood Nutrition Package Intervention project, the study enrolled 1 078 children aged 5-7 years from four counties in Henan (Songxian and Ruyang countries) and Guizhou (Guiding and Fuquan countries) provinces. Using BMI Z-scores, 87 overweight and obese(OVOB) children were selected and matched by sex, age, and BMI Z-score with 117 normal-weight controls. Participants were further stratified into four metabolic phenotype groups: metabolically healthy normal weight (MHNW, n=51), metabolically unhealthy normal weight (MUNW, n=66), metabolically healthy obesity (MHO, n=31) and metabolically unhealthy obesity (MUO, n=56) based on four conventional cardiometabolic risk factor (CR) criteria. Data were collected through questionnaires, anthropometric measurements, serum biochemical tests, and KASP genotyping. The distribution of three genetic polymorphisms (CDKAL1 rs35261542, FAIM2 rs3205718, VGLL4 rs2574704) across metabolic subgroups was analyzed. Multivariate Logistic regression models assessed associations between these polymorphisms and obesity/metabolic phenotypes. Results Multivariate Logistic regression analysis showed that Homozygous mutant AA genotype of CDKAL1 rs35261542 was positively associated with OVOB(OR=3.63), MHO (OR=11.04), MUO (OR=4.88) (P < 0.05). Homozygous TT genotype of FAIM2 rs3205718 increased OVOB risk (OR=4.44, P < 0.05) but showed no association with metabolic phenotypes (P>0.05). Homozygous mutant TT of VGLL4 rs2574704 reduced the risks of MHO and MUO (OR=0.30, 0.24, P < 0.05). Cumulative genetic effects analysis demonstrated carriers of 1 or 2 risk genotypes of rs35261542 and rs3205718 had progressively higher OVOB risk (OR=2.53, 20.79), and the combination of rs35261542 and rs2574704 increased risks for both MHO (OR=8.50) and MUO (OR=5.00) (P < 0.05). Conclusions The AA genotype of rs35261542 (CDKAL1) positively correlates with childhood obesity and metabolic abnormalities. The TT genotype of rs3205718 (FAIM2) increases obesity risk but not metabolic phenotypes. The TT genotype of rs2574704 (VGLL4) shows protective effects against metabolic dysfunction. Risk genotypes exhibit dose-dependent cumulative effects on obesity and metabolic outcomes.
- Child,
- Obesity,
- Genes,
- Metabolic diseases,
- Regression analysis

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References(28)

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