title: Physical activity and sedentary behavior can modulate the effect of the PNPLA3 variant on childhood NAFLD: a case-control study in a Chinese population.
abstract: BACKGROUND
  The patatin like phospholipase containing domain 3 gene (PNPLA3) rs738409 C > G polymorphism, one of the most important gene polymorphisms involved in hepatic steatosis, has been reported to interact with different nutrients and dietary patterns on Non-Alcoholic Fatty Liver Disease (NAFLD), but no studies have focused on its interaction with physical activity or sedentary behavior. Therefore, this study aims at determining whether physical activity or sedentary behavior could modulate the effect of the PNPLA3 variant on childhood NAFLD.
  
  
  METHODS
  A case-control study was conducted including 1027 Chinese children aged 7-18 years old (162 children with NAFLD and 865 children without). The anthropometric measurements, liver ultrasound examination, questionnaires and genotyping of the PNPLA3 rs738409 polymorphism were performed.
  
  
  RESULTS
  Stratified analyses showed that the proportions of NAFLD increased with the G-allele number only in children who did not have enough physical activity (physical activity < 1 h/d) (OR 3.05, 95% CI 1.82-5.12, P < 0.001), and in children with a sedentary lifestyle (sedentary behavior ≥ 2 h/d) (OR 3.41, 95% CI 1.88-6.18, P < 0.001). Significant interactions on childhood NAFLD were found between the G-allele number in the PNPLA3 rs738409 polymorphism and behaviors, including physical activity (P = 0.001), sedentary behavior (P = 0.010) and the combination of physical activity and sedentary behavior (P < 0.001).
  
  
  CONCLUSIONS
  This is the first study to report the interaction between the PNPLA3 rs738409 polymorphism and physical activity or sedentary behavior on NAFLD, providing new clues on the function of the PNPLA3 gene, which will also be useful for future risk assessment and personalized treatment of NAFLD.
authors.affiliation: Institute of Child and Adolescent Health of Peking University, School of Public Health, Peking University Health Science Center, Beijing, 100191, China.|Interdisciplinary Center for Network Science and Applications (iCeNSA), University of Notre Dame, Notre Dame, IN, 46556, USA.
authors.forename: Shuo
authors.initials: S
authors.lastname: Wang
authors.affiliation: Institute of Child and Adolescent Health of Peking University, School of Public Health, Peking University Health Science Center, Beijing, 100191, China.
authors.forename: Jieyun
authors.initials: J
authors.lastname: Song
authors.affiliation: Institute of Child and Adolescent Health of Peking University, School of Public Health, Peking University Health Science Center, Beijing, 100191, China.|Beijing Obstetrics and Gynecology Hospital, Capital Medical University,Beijing Maternal and Child Health Care Hospital, Beijing, 100026, China.
authors.forename: Xiaorui
authors.initials: X
authors.lastname: Shang
authors.affiliation: Interdisciplinary Center for Network Science and Applications (iCeNSA), University of Notre Dame, Notre Dame, IN, 46556, USA.
authors.forename: Nitesh
authors.initials: N
authors.lastname: Chawla
authors.affiliation: Institute of Child and Adolescent Health of Peking University, School of Public Health, Peking University Health Science Center, Beijing, 100191, China.
authors.forename: Yide
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Institute of Child and Adolescent Health of Peking University, School of Public Health, Peking University Health Science Center, Beijing, 100191, China.|Centre for Population Health Sciences, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, Scotland, UK.
authors.forename: Xiangrui
authors.initials: X
authors.lastname: Meng
authors.affiliation: Institute of Child and Adolescent Health of Peking University, School of Public Health, Peking University Health Science Center, Beijing, 100191, China. whjun1@bjmu.edu.cn.
authors.forename: Haijun
authors.initials: H
authors.lastname: Wang
authors.affiliation: Institute of Child and Adolescent Health of Peking University, School of Public Health, Peking University Health Science Center, Beijing, 100191, China. majunt@bjmu.edu.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
mesh_terms: D000293:Adolescent; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D015444:Exercise; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008049:Lipase / Q000235:genetics*; D008099:Liver / Q000000981:diagnostic imaging; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D065626:Non-alcoholic Fatty Liver Disease / Q000000981:diagnostic imaging / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D057185:Sedentary Behavior; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
chemical_list: D008049:Lipase; D008565:Membrane Proteins; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
keywords: Child and adolescent; Non-Alcoholic Fatty Liver Disease; Patatin like phospholipase containing domain 3 gene; Physical activity; Sedentary behavior