Genetic Associations and Interactions Between the NR3C1 (GR) and NR3C2 (MR) Genes and Aggressive Behavior in a Central South Chinese Han Population

Genet Test Mol Biomarkers. 2017 Aug;21(8):497-505. doi: 10.1089/gtmb.2016.0417. Epub 2017 Jul 7.

Abstract

Aims: The glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) play important roles in the hypothalamic-pituitary-adrenal axis and stress regulation. The current study aimed to address the genetic association and gene-gene interactions between GR and MR gene polymorphisms and aggressive behavior.

Methods: A haplotype-based, case-control study was designed to examine the association between human MR and GR genes and aggressive behaviors, including robbery and intentional interpersonal injury, in a central south Chinese Han population. Eight well-studied polymorphisms of the MR gene (rs2070951, rs2871, rs5522, and rs5525) and the GR gene (rs10482605, rs6190, rs1800445, and rs6196) were genotyped using SNaPshot.

Results: The MR and GR gene polymorphisms were not associated with aggressive behaviors, including in robbery and intentional interpersonal injury subgroups (p > 0.05). The frequency of haplotype TAAT of GR was significantly higher in the control group than that in the case group (p = 0.004, padj = 0.02). In addition, a two-way interaction between GR rs1800445 and MR rs2070951 and aggressive behavior was also found (p = 0.01).

Conclusions: The haplotype TAAT of GR might be a protective factor against aggressive behavior, while gene-gene interactions between GR rs1800445 and MR rs2070951 might be a risk factor for aggressive behavior in the Central South Chinese Han population.

Keywords: gene–gene interaction; glucocorticoid receptor (GR); mineralocorticoid receptor (MR); polymorphism.

MeSH terms

  • Adult
  • Aggression / physiology
  • Case-Control Studies
  • China
  • Ethnicity / genetics
  • Genetic Association Studies / methods
  • Genetic Predisposition to Disease
  • Genotype
  • Haplotypes
  • Humans
  • Hypothalamo-Hypophyseal System
  • Male
  • Middle Aged
  • Pituitary-Adrenal System
  • Polymorphism, Single Nucleotide
  • Receptors, Glucocorticoid / genetics*
  • Receptors, Glucocorticoid / metabolism
  • Receptors, Mineralocorticoid / genetics*
  • Receptors, Mineralocorticoid / metabolism
  • Stress, Psychological / genetics

Substances

  • NR3C1 protein, human
  • NR3C2 protein, human
  • Receptors, Glucocorticoid
  • Receptors, Mineralocorticoid