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Gene-gene interactions and associations of six hypertension related single nucleotide polymorphisms with obesity risk in a Chinese children population

Gene. 2018 Dec 30:679:320-327. doi: 10.1016/j.gene.2018.09.019. Epub 2018 Sep 12.

Abstract

Obesity is a major risk for hypertension. However, the associations between hypertension susceptibility loci and the risk of obesity as well as the effects of gene-gene interactions are unclear, especially in the Chinese children population. Six single nucleotide polymorphisms (SNPs) (ATP2B1 rs17249754, CSK rs1378942, MTHFR rs1801133, CYP17A1 rs1004467, STK39 rs3754777, FGF5 rs16998073) were genotyped for 3503 Chinese children, aged 6-18 years. Of them, 758 obese cases and 2745 controls were identified based on the International Obesity Task Force age- and sex-specific BMI references. Among the six SNPs, three were associated with obesity risk (CSK rs1378942: odds ratio (OR) = 1.20, 95% confidence interval (CI) 1.01-1.43, P = 0.042; MTHFR rs1801133: OR = 1.19, 95% CI 1.05-1.34, P = 0.006; FGF5 rs16998073: OR = 1.14, 95% CI 1.00-1.29, P = 0.047). The genetic risk score (GRS), based on these three SNPs (CSK rs1378942, MTHFR rs1801133, FGF5 rs16998073), showed a positive association with risk of obesity (OR = 1.18, 95% CI 1.09-1.28, P = 7.60 × 10-5). The same association signals were also detected in the subgroups of puberty and inactivity. In addition, interaction analyses among these loci implied a potential gene-gene interaction between MTHFR and FGF5. These findings show a significant association of hypertension susceptibility loci in Chinese children, suggesting a likely influence of genetic and environmental factors on the risk of obesity.

Keywords: Body mass index; Chinese children; Interaction; Obesity; Polymorphism.

MeSH terms

  • Adolescent
  • Asian People / genetics*
  • CSK Tyrosine-Protein Kinase
  • Child
  • China
  • Cross-Sectional Studies
  • Epistasis, Genetic
  • Female
  • Genetic Association Studies
  • Humans
  • Hypertension / genetics*
  • Male
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics*
  • Obesity / genetics*
  • Polymorphism, Single Nucleotide*
  • Receptor, Fibroblast Growth Factor, Type 5 / genetics*
  • src-Family Kinases / genetics*

Substances

  • FGFRL1 protein, human
  • Receptor, Fibroblast Growth Factor, Type 5
  • MTHFR protein, human
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • CSK Tyrosine-Protein Kinase
  • src-Family Kinases
  • CSK protein, human