title: The gene-gene interaction of INSIG-SCAP-SREBP pathway on the risk of obesity in Chinese children.
abstract: BACKGROUND
  Childhood obesity has become a global public health problem in recent years. This study aimed to explore the association of genetic variants in INSIG-SCAP-SREBP pathway with obesity in Chinese children.
  
  
  METHODS
  A case-control study was conducted, including 705 obese cases and 1,325 nonobese controls. We genotyped 15 single nucleotide polymorphisms (SNPs) of five genes in INSIG-SCAP-SREBP pathway, including insulin induced gene 1 (INSIG1), insulin induced gene 2 (INSIG2), SREBP cleavage-activating protein gene (SCAP), sterol regulatory element binding protein gene 1 (SREBP1), and sterol regulatory element binding protein gene 2 (SREBP2). We used generalized multifactor dimensionality reduction (GMDR) and logistic regression to investigate gene-gene interactions.
  
  
  RESULTS
  Single polymorphism analyses showed that SCAP rs12487736 and rs12490383 were nominally associated with obesity. We identified a 3-locus interaction on obesity in GMDR analyses (P = 0.001), involving 3 genetic variants of INSIG2, SCAP, and SREBP2. The individuals in high-risk group of the 3-locus combinations had a 79.9% increased risk of obesity compared with those in low-risk group (OR = 1.799, 95% CI: 1.475-2.193, P = 6.61 × 10(-9)).
  
  
  CONCLUSIONS
  We identified interaction of three genes in INSIG-SCAP-SREBP pathway on risk of obesity, revealing that these genes affect obesity more likely through a complex interaction pattern than single gene effect.
authors.affiliation: School of Public Health, Institute of Child and Adolescent Health, Peking University, No. 38 Xueyuan Road, Haidian District, Beijing 100191, China.
authors.forename: Fang-Hong
authors.initials: FH
authors.lastname: Liu
authors.affiliation: School of Public Health, Institute of Child and Adolescent Health, Peking University, No. 38 Xueyuan Road, Haidian District, Beijing 100191, China.
authors.forename: Jie-Yun
authors.initials: JY
authors.lastname: Song
authors.affiliation: School of Public Health, Institute of Child and Adolescent Health, Peking University, No. 38 Xueyuan Road, Haidian District, Beijing 100191, China.
authors.forename: Xiao-Rui
authors.initials: XR
authors.lastname: Shang
authors.affiliation: School of Public Health, Institute of Child and Adolescent Health, Peking University, No. 38 Xueyuan Road, Haidian District, Beijing 100191, China.
authors.forename: Xiang-Rui
authors.initials: XR
authors.lastname: Meng
authors.affiliation: School of Public Health, Institute of Child and Adolescent Health, Peking University, No. 38 Xueyuan Road, Haidian District, Beijing 100191, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
authors.affiliation: School of Public Health, Institute of Child and Adolescent Health, Peking University, No. 38 Xueyuan Road, Haidian District, Beijing 100191, China.
authors.forename: Hai-Jun
authors.initials: HJ
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D044466:Asian People; D016022:Case-Control Studies; D002648:Child; D002681:China; D004843:Epistasis, Genetic; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009765:Obesity / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D012307:Risk Factors; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics*; D051782:Sterol Regulatory Element Binding Protein 2 / Q000235:genetics*
chemical_list: C108626:INSIG1 protein, human; C467727:INSIG2 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C497387:SREBF1 protein, human; C497390:SREBF2 protein, human; C102196:SREBP cleavage-activating protein; D051780:Sterol Regulatory Element Binding Protein 1; D051782:Sterol Regulatory Element Binding Protein 2