title: [Impact of obesity-related gene polymorphism on risk of obesity and metabolic disorder in childhood].
abstract: OBJECTIVE
  To examine the impact of single nucleotide polymorphisms in obesity-related genes on risk of obesity and metabolic disorder in childhood.
  
  
  METHODS
  A total of 3 503 Chinese children aged 6 to 18 years participated in the study, including 1 229 obese, 655 overweight and 1 619 normal weight children (diagnosed by the Chinese age- and sex- specific BMI cutoffs). Body size parameters were assessed and venipuncture blood samples were collected after a 12-hour overnight fast. Plasma glucose, insulin and serum lipid profiles were measured.Genomic DNA was isolated from peripheral blood white cells using the salt fractionation method. A total of 11 single nucleotide polymorphisms were genotyped by TaqMan allelic discrimination assays with the GeneAmp 7900 sequence detection system (Applied Biosystems, Foster City, CA, USA) (FTO rs9939609, MC4R rs17782313, GNPDA2 rs10938397, FAIM2 rs7138803, BDNF rs6265, NPC1 rs1805081, PCSK1 rs6235, KCTD15 rs29941, BAT2 rs2844479, SEC16B rs10913469 and SH2B1 rs4788102). Multiple factor analysis was performed to estimate the association between the variant and obesity-related traits. The false discovery rate (FDR) approach was used to correct for multiple comparisons.
  
  
  RESULTS
  After sex, age and pubertal stage adjustment and correction for multiple testing, the rs9939609-A, rs17782313-C, rs10938397-G, and rs7138803-A alleles were associated with higher BMI (β = 0.352-0.747), fat mass percentage(β = 0.568-1.113), waist circumference (β = 0.885-1.649) and waist-to-height ratio(β = 0.005-0.010) (all P values < 0.01) in Chinese children. The rs6265-G allele increased BMI(β = 0.251, P = 0.020). The rs9939609-A, rs17782313-C, and rs10938397-G and rs6265-G alleles were also associated with risk of obesity (OR = 1.386, 95%CI:1.171-1.642; OR = 1.367, 95%CI:1.196-1.563; OR = 1.242, 95%CI:1.102-1.400; OR = 1.156, 95%CI:1.031-1.296).Rs7138803 was associated with risk of obesity only in boys (OR = 1.234, 95%CI:1.043-1.460). GNPDA2 rs10938397-G allele was associated with risk of insulin resistance(OR = 1.205, 95%CI:1.069-1.359), but there was no significance after adjusting for BMI.
  
  
  CONCLUSIONS
  The association of FTO rs9939609-A, MC4R rs17782313-C, GNPDA2 rs10938397-G, and FAIM2 rs7138803-A with higher BMI, fat mass percentage, waist circumference, and waist-to height ratio and risk of obesity, and BDNF rs6265-G allele may increase BMI and obesity risk in Chinese children. GNPDA2 rs10938397-G may increase the risk of childhood insulin resistance depending on BMI.
authors.affiliation: Department of Epidemiology, Capital Institute of Pediatrics, Beijing 100020, China.
authors.forename: Meixian
authors.initials: M
authors.lastname: Zhang
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Zhao
authors.forename: Bo
authors.initials: B
authors.lastname: Xi
authors.forename: Yue
authors.initials: Y
authors.lastname: Shen
authors.forename: Lijun
authors.initials: L
authors.lastname: Wu
authors.forename: Hong
authors.initials: H
authors.lastname: Cheng
authors.forename: Dongqing
authors.initials: D
authors.lastname: Hou
authors.affiliation: Email: jiemi@vip.163.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Mi
mesh_terms: D000293:Adolescent; D000483:Alleles; D044466:Asian People; D015992:Body Mass Index; D002648:Child; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008659:Metabolic Diseases; D009765:Obesity; D050177:Overweight; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D055105:Waist Circumference