title: Associations of obesity susceptibility loci with hypertension in Chinese children.
abstract: BACKGROUND
  Recent genome-wide association studies have identified several single-nucleotide polymorphisms (SNPs) that are associated with body mass index (BMI)/obesity.
  
  
  OBJECTIVE
  As obesity is an independent risk factor for hypertension, the objective of the study was to investigate the associations of obesity susceptibility loci with blood pressure (BP)/hypertension in a population of Chinese children.
  
  
  METHODS
  This was a genotype-phenotype association study. Participants included 3077 Chinese children, aged 6-18 years. Based on the Chinese age- and sex-specific BP standards, 619 hypertensive cases and 2458 controls with normal BP were identified.
  
  
  METHODS
  BP was measured by auscultation using a standard clinical sphygmomanometer.
  
  
  RESULTS
  Of the 11 SNPs, only FTO rs9939609 was significantly associated with systolic BP (SBP; P=0.034) and three SNPs were significantly associated with diastolic BP (DBP; GNPDA2 rs10938397: P=0.026; FAIM2 rs7138803: P=0.015; NPC1 rs1805081: P=0.031) after adjustment for age, sex and hypertension status. In addition, three SNPs were significantly associated with hypertension risk after adjustment for age and sex (FTO rs9939609: odds ratio (OR)=1.35, 95% confidence interval (CI) 1.12-1.62, P=0.001; MC4R rs17782313: OR=1.22, 95% CI 1.06-1.42, P=0.007; GNPDA2 rs10938397: OR=1.17, 95% CI 1.02-1.34, P=0.021). After additional adjustment for BMI, none remained significant. The genetic risk score (GRS), based on three significant SNPs (FTO rs9939609, MC4R rs17782313, GNPDA2 rs10938397), showed a positive association with SBP (P=5.17 × 10(-4)) and risk of hypertension (OR=1.22, 95% CI 1.12-1.33, P=6.07 × 10(-6)). Further adjustment for BMI abolished the positive associations (SBP: P=0.220; DBP: P=0.305; hypertension: P=0.052). Only FTO rs9939609 and GRS were statistically associated with hypertension risk in the age- and sex-adjusted model after correction for multiple testing.
  
  
  CONCLUSIONS
  The present study demonstrated that FTO rs9939609 and combined SNPs were significantly associated with risk of hypertension, which seems to be dependent on BMI.
authors.affiliation: Department of Maternal and Child Health Care, School of Public Health, Shandong University, Jinan, China.
authors.forename: B
authors.initials: B
authors.lastname: Xi
authors.forename: X
authors.initials: X
authors.lastname: Zhao
authors.forename: Y
authors.initials: Y
authors.lastname: Shen
authors.forename: L
authors.initials: L
authors.lastname: Wu
authors.forename: K
authors.initials: K
authors.lastname: Hotta
authors.forename: D
authors.initials: D
authors.lastname: Hou
authors.forename: H
authors.initials: H
authors.lastname: Cheng
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.forename: J
authors.initials: J
authors.lastname: Mi
mesh_terms: D000293:Adolescent; D017677:Age Distribution; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D044466:Asian People / Q000235:genetics; D001794:Blood Pressure; D015992:Body Mass Index; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics; D002648:Child; D002681:China / Q000453:epidemiology; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D006973:Hypertension / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D016017:Odds Ratio; D063766:Pediatric Obesity / Q000453:epidemiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D044105:Receptor, Melanocortin, Type 4 / Q000235:genetics; D012307:Risk Factors; D017678:Sex Distribution; D011795:Surveys and Questionnaires
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C470072:MC4R protein, human; D011506:Proteins; D044105:Receptor, Melanocortin, Type 4; C579455:BDNF protein, human; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human