title: Influence of obesity on association between genetic variants identified by genome-wide association studies and hypertension risk in Chinese children.
abstract: BACKGROUND
  Childhood hypertension is a complex disease influenced by both genetic and environmental factors. We aimed to examine how obesity status influences the association of 6 single nucleotide polymorphisms (SNPs) identified by genome-wide association studies (GWASs) with systolic/diastolic blood pressure (SBP/DBP) and hypertension in Chinese children.
  
  
  METHODS
  We recruited 619 hypertensive case subjects and 2,458 individuals with normal blood pressure from the Beijing Child and Adolescent Metabolic Syndrome study, a population-based case-control study. We selected 6 SNPs from earlier GWASs of hypertension and genotyped them using TaqMan assay.
  
  
  RESULTS
  In the normal weight group, we did not observe any significant association of 6 SNPs and the genetic risk score (GRS) with SBP/DBP and hypertension (all P > 0.05). Only STK39 rs3754777 was significantly associated with higher DBP (P = 0.02) in the overweight subjects. In the obese group, 3 SNPs and the GRS were significantly associated with higher SBP (ATP2B1 rs17249754: P = 0.02; CSK rs1378942: P = 0.003; CYP17A1 rs1004467: P = 0.04; GRS: P = 0.0002). We also observed a significant association of 4 SNPs and the GRS with hypertension (ATP2B1 rs17249754: P = 0.02; CSK rs1378942: P = 0.02; CYP17A1 rs1004467: P = 0.02; MTHFR rs1801133: P = 0.03; GRS: P = 0.0004). Correction for multiple testing had no influence on the statistical significance of the association of GRS with SBP/hypertension.
  
  
  CONCLUSIONS
  This study shows a significant association of hypertension susceptibility loci only in obese Chinese children, suggesting a likely influence of childhood obesity on the risk of hypertension.
authors.affiliation: Department of Maternal and Child Health Care, School of Public Health, Shandong University, Jinan, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Xi
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Zhao
authors.forename: Giriraj R
authors.initials: GR
authors.lastname: Chandak
authors.forename: Yue
authors.initials: Y
authors.lastname: Shen
authors.forename: Hong
authors.initials: H
authors.lastname: Cheng
authors.forename: Dongqing
authors.initials: D
authors.lastname: Hou
authors.forename: Xingyu
authors.initials: X
authors.lastname: Wang
authors.forename: Jie
authors.initials: J
authors.lastname: Mi
mesh_terms: D000293:Adolescent; D000081247:CSK Tyrosine-Protein Kinase; D016022:Case-Control Studies; D002648:Child; D002681:China; D005260:Female; D051521:Fibroblast Growth Factor 5 / Q000235:genetics; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000235:genetics*; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D009765:Obesity / Q000150:complications*; D050177:Overweight / Q000150:complications; D053499:Plasma Membrane Calcium-Transporting ATPases / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics; D019061:src-Family Kinases / Q000235:genetics
chemical_list: C506952:ATP2B1 protein, human; C496449:FGF5 protein, human; D051521:Fibroblast Growth Factor 5; C501892:CYP17A1 protein, human; D013254:Steroid 17-alpha-Hydroxylase; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human; D017346:Protein Serine-Threonine Kinases; C486409:STK39 protein, human; D053499:Plasma Membrane Calcium-Transporting ATPases
keywords: Chinese children; blood pressure; genetic risk score; hypertension; obesity; polymorphism.