Influence of obesity on association between genetic variants identified by genome-wide association studies and hypertension risk in Chinese children

Am J Hypertens. 2013 Aug;26(8):990-6. doi: 10.1093/ajh/hpt046. Epub 2013 Apr 16.

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.

Keywords: Chinese children; blood pressure; genetic risk score; hypertension; obesity; polymorphism..

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • CSK Tyrosine-Protein Kinase
  • Case-Control Studies
  • Child
  • China
  • Female
  • Fibroblast Growth Factor 5 / genetics
  • Gene-Environment Interaction
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Hypertension / complications
  • Hypertension / genetics*
  • Male
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics
  • Obesity / complications*
  • Overweight / complications
  • Plasma Membrane Calcium-Transporting ATPases / genetics
  • Polymorphism, Single Nucleotide
  • Protein-Serine-Threonine Kinases / genetics
  • Steroid 17-alpha-Hydroxylase / genetics
  • src-Family Kinases / genetics

Substances

  • ATP2B1 protein, human
  • FGF5 protein, human
  • Fibroblast Growth Factor 5
  • CYP17A1 protein, human
  • Steroid 17-alpha-Hydroxylase
  • MTHFR protein, human
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • CSK Tyrosine-Protein Kinase
  • src-Family Kinases
  • CSK protein, human
  • Protein-Serine-Threonine Kinases
  • STK39 protein, human
  • Plasma Membrane Calcium-Transporting ATPases