ABSTRACT
OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) has significant genetic susceptibility. Adipocytokines play a crucial role in NAFLD development by participating in insulin resistance and hepatic steatosis. However, the association between adipocytokine pathway genes and NAFLD remains unclear. This study aims to explore the association of gene polymorphisms in the adipocytokine pathway and their interactions with NAFLD in obese children. METHODS: A case-control study was conducted, dividing obese children into NAFLD and control groups. Peripheral venous blood (2 mL) was collected from each participant for DNA extraction. A total of 14 single nucleotide polymorphisms (SNP) in the adipocytokine pathway were genotyped using multiplex PCR and high-throughput sequencing. Univariate and multivariate Logistic regression analyses were used to assess the association between SNP and NAFLD in obese children. Dominant models were used to analyze additive and multiplicative interactions via crossover analysis and Logistic regression. Generalized multifactor dimensionality reduction (GMDR) was used to detect gene-gene interactions among the 14 SNPs and their association with NAFLD in obese children. RESULTS: A total of 1 022 children were included, with 511 in the NAFLD group and 511 in the control group. After adjusting for age, gender, and BMI, multivariate Logistic regression showed that PPARG rs1801282 was associated with NAFLD in the obese children in 3 genetic models: heterozygote model (CG vs CC, OR=0.58, 95% CI 0.36 to 0.95, P=0.029), dominant model (GG+CG vs CC, OR=0.62, 95% CI 0.38 to 1.00, P=0.049), and overdominant model (CC+GG vs CG, OR=1.72, 95% CI 1.06 to 2.80, P=0.028). PRKAG2 rs12703159 was associated with NAFLD in 4 genetic models: heterozygous model (CT vs CC, OR=1.51, 95% CI 1.10 to 2.07, P=0.011), dominant model (CT+TT vs CC, OR=1.50, 95% CI 1.10 to 2.03, P=0.010), overdominant model (CC+TT vs CT, OR=0.67, 95% CI 0.49 to 0.92, P=0.012), and additive model (CC vs CT vs TT, OR=1.40, 95% CI 1.07 to 1.83, P=0.015). No significant multiplicative or additive interaction between PPARG rs1801282 and PRKAG2 rs12703159 was found in association with NAFLD. GMDR analysis, adjusted for age, gender, and BMI, revealed no statistically significant interactions among the 14 SNPs (all P>0.05). CONCLUSIONS: Mutations in PPARG rs1801282 and PRKAG2 rs12703159 are associated with NAFLD in obese children. However, no gene-gene interactions among the SNP are found to be associated with NAFLD in obese children.
Subject(s)
Adipokines , Genetic Predisposition to Disease , Non-alcoholic Fatty Liver Disease , Polymorphism, Single Nucleotide , Humans , Non-alcoholic Fatty Liver Disease/genetics , Non-alcoholic Fatty Liver Disease/complications , Child , Case-Control Studies , Male , Female , Adipokines/genetics , Adipokines/blood , Obesity/genetics , Obesity/complications , PPAR gamma/genetics , Adolescent , Pediatric Obesity/genetics , Pediatric Obesity/complicationsABSTRACT
OBJECTIVES: Insulin signaling pathway plays an important role in metabolic associated fatty liver disease (MAFLD), however, the association between polymorphisms of genes related to insulin signaling pathway and MAFLD remains unclear. This study aims to investigate the association between insulin signaling pathway-related gene polymorphisms and gene-gene interactions with MAFLD susceptibility in obese children so as to provide scientific basis for further study of genetic mechanism. METHODS: A total of 502 obese children with MAFLD who admitted to Hunan Provincial Children's Hospital from September 2019 to October 2021, were recruited as a case group, and 421 obese children with non-MAFLD admitted during the same period were recruited as a control group. Socio-demographic information, preterm birth history, eating habits, and exercise status of the subjects were collected by inquiry survey, and anthropometric information was collected by physical measurement. At the same time, 2 mL of venous blood was collected to extract DNA, and the polymorphism of insulin signaling pathway-related genes (5 representative candidate genes, 12 variants) was detected. Multivariate Logistic regression analysis was used to investigate the association between insulin signaling pathway-related gene polymorphisms and MAFLD in obese children. RESULTS: After adjusting for confounder factors, INS rs3842748 was significantly associated with the risk of MAFLD in obese children in allele, heterozygous, and dominant models [OR and 95% CI 1.749 (1.053 to 2.905), 1.909 (1.115 to 3.267), 1.862 (1.098 to 3.157), all P<0.05]; INS rs3842752 was significantly associated with the risk of MAFLD in obese children in heterozygous and dominant models [OR and 95% CI 1.736 (1.028 to 2.932), 1.700 (1.015 to 2.846), all P<0.05]. NR1H3 rs3758674 was significantly correlated with the risk of MAFLD in obese children in allele model [OR and 95% CI 0.716 (0.514 to 0.997), P<0.05]. SREBP-1c rs2297508 was significantly associated with the risk of MAFLD in obese children in allele and dominant models [OR and 95% CI 0.772 (0.602 to 0.991) and 0.743 (0.557 to 0.991), all P<0.05]. SREBP-1c rs8066560 was significantly associated with the risk of MAFLD in obese children in allele, heterozygous, and dominant models [OR and 95% CI 0.759 (0.589 to 0.980), 0.733 (0.541 to 0.992), 0.727 (0.543 to 0.974), all P<0.05]. NR1H3 rs3758674 mutant C and SREBP-1c rs2297508 mutant G had interaction in the development of MAFLD in obese children [OR and 95% CI 0.407 (0.173 to 0.954), P<0.05]. CONCLUSIONS: The INS, NR1H3, and SREBP-1c gene polymorphisms in the insulin signaling pathway are associated with the susceptibility of MAFLD in obese children, but the functions and mechanisms of these genes need to be further studied.
Subject(s)
Insulins , Non-alcoholic Fatty Liver Disease , Pediatric Obesity , Premature Birth , Child , Infant, Newborn , Humans , Female , Pediatric Obesity/genetics , Sterol Regulatory Element Binding Protein 1 , Signal Transduction/geneticsABSTRACT
BACKGROUND: It had been reported that the increase in the prevalence of childhood overweight and obesity in several developed countries over the decade was largely a consequence of changes in the upper end of the body mass index (BMI) distribution. We speculated that the change in BMI distribution among Chinese children is different from that in developed countries. Therefore, we investigated the changes in the BMI distribution among urban children in Changsha, China. METHODS: A secondary data analysis of the 2002 and 2018 Annual Survey on Students' Constitution and Health from Yuhua District, Changsha City, China was performed. The BMI distribution of children aged 6-15 years (n=72,061) was examined by calculating the BMI value at 5th, 50th, 85th, and 95th percentiles. Differences in the BMI value at the 5th, 50th, 85th, and 95th percentiles between 2002 and 2018 according to age and sex were calculated. RESULTS: From 2002 to 2018, the standardized rate of underweight decreased from 6.9% to 3.4%, whereas that of obesity increased from 6.1% to 13.8%. The BMI of the population increased over the 16-year period. The greatest change between the years was seen in the 85th percentile, and moderate changes were seen in the 5th and 50th BMI percentiles. Also, the greatest changes in the BMI percentiles were evident at age 12-14 years. CONCLUSIONS: The whole spectrum of BMI distribution among school-aged children shifted over the 16-year study period, although the increases were more marked in the upper than lower percentiles. Health professionals and health policymakers should develop strategies and interventions aimed at preventing adverse health effects caused by this change.
ABSTRACT
BACKGROUND: To investigate trends in the prevalence of reduced visual acuity (VA), a proxy measure for myopia, in an urban district in China. METHODS: Data were extracted from the dataset of the 2002 and 2018 Annual Survey on Students' Constitution and Health from Yuhua District, Changsha City, China. Children aged 6-15 years were included in the study. VA was measured using a LogMAR tumbling E chart. The prevalence of reduced VA was calculated by age and gender. The chi-square test was used to compare the differences between groups. RESULTS: The final VA analysis included 26217 children in 2002 and 45510 children in 2018. The overall prevalence of reduced VA increased from 28.3% in 2002 to 46.5% in 2018 (P < 0.001). The prevalence of reduced VA started to increase markedly from the age of 14 years in 2002, while in 2018 it started to increase markedly from the age of 9 years. The prevalence of severely reduced VA increased in all age groups from 2002 to 2018 and increased with age (all P < 0.001). In 2002, over 50% of children in all age groups had normal VA. By 2018, the prevalence of normal VA decreased from 61.4% in those aged 6 years to 31.9% in those aged 15 years. CONCLUSIONS: The prevalence of reduced VA among children aged 6-15 years in Yuhua District has become more common with age, and there has been a marked increase in the prevalence of reduced VA from 2002 to 2018. The remarkable epidemic of reduced VA started 5 years earlier in 2018 than in 2002. Evidence from the present study suggests that interventions should be launched before the age of 9 years.