A common variant in the peroxisome proliferator-activated receptor-γ coactivator-1α gene is associated with nonalcoholic fatty liver disease in obese children
Journal
American Journal of Clinical Nutrition
Journal Volume
97
Journal Issue
2
Pages
326-331
Date Issued
2013
Author(s)
Abstract
Background: The single nucleotide polymorphism in the peroxi-some proliferator-activated receptor-γ coactivator (PGC)-1a gene (PPARGC1A) was identified to be associated with nonalcoholic fatty liver disease (NAFLD) in adults. The PPARGC1A gene encodes PGC-1α, which regulates cellular energy metabolism. Objective: We aimed to test the hypothesis that the PPARGC1A rs8192678 risk A allele would influence the risk of NAFLD in obese children. Design: We genotyped PPARGC1A rs8192678 and PNPLA3 rs738409 in 781 obese children aged 7-18 y. NAFLD was determined by ultrasonography. We evaluated the independent influence of the PPARGC1A rs8192678 risk A allele on pediatric NAFLD after control for the effect of the PNPLA3 rs738409 polymorphism. Results: A total of 23.3% of the recruited obese children had NAFLD. PNPLA3 rs738409 increased the OR of NAFLD by 1.622 (95% CI: 1.071, 2.457; P = 0.023) in subjects with GC alleles and 2.659 (95% CI: 1.509, 4.686; P < 0.001) for GG alleles, as compared with CC alleles. After control for the effects of age- and sex-adjusted BMI, sex, and PNPLA3 rs738409 polymorphism, the PPARGC1A rs8192678 risk A allele was an independent risk factor for developing NAFLD, with an OR of 1.740 (95% CI: 1.149, 2.637; P = 0.009). Subjects with the PPARGC1A rs8192678 risk A allele had an increase in the mean serum alanine aminotransferase concentration of 5.2 IU/L, as compared with subjects without this allele (P = 0.011). Conclusion: The PPARGC1A rs8192678 risk A allele is associated with an increased risk of NAFLD, independent of the effect of the PNPLA3 rs738409 polymorphism in our population of obese Taiwanese children. ? 2013 American Society for Nutrition.
SDGs
Other Subjects
alanine aminotransferase; aspartate aminotransferase; gamma glutamyltransferase; patatin like phospholipase 3; peroxisome proliferator activated receptor gamma coactivator 1alpha; phospholipase; unclassified drug; adolescent; adult; alanine aminotransferase blood level; article; aspartate aminotransferase blood level; child; childhood obesity; controlled study; diastolic blood pressure; female; gene frequency; genetic variability; genotype; human; insulin resistance; major clinical study; male; nonalcoholic fatty liver; oxidative stress; risk factor; school child; single nucleotide polymorphism; systolic blood pressure; waist circumference; Adolescent; Alleles; Body Mass Index; Child; Cohort Studies; Fatty Liver; Female; Genetic Association Studies; Genetic Predisposition to Disease; Heat-Shock Proteins; Heterozygote; Homozygote; Humans; Lipase; Liver; Male; Membrane Proteins; Obesity; Polymorphism, Single Nucleotide; Taiwan; Transcription Factors; Waist Circumference
Type
journal article