NR3C1参与HPA轴调节,与应激相关的身心疾病关系密切。以往针对NR3C1与焦虑障碍的研究基本以成人为考察对象,且大多关注负性生活事件等个体层面环境变量。本研究采用病例-对照设计,以238名青少年为被试(焦虑障碍117人,对照121人),旨在考察NR3C1常见位点rs6191、rs6196、rs41423247的多态性、单倍型以及父母不同类型教养方式对焦虑障碍的影响。结果表明rs6191 GG基因型、rs6196 AA基因型、rs41423247 GG基因型与低焦虑障碍风险相关。父母过多的过度保护与冷漠拒绝、父亲过少的温暖关怀可预测较高的焦虑障碍风险。rs41423247多态性与母亲温暖关怀存在交互作用:rs41423247 GG基因型只在母亲温暖关怀较多时能降低焦虑障碍风险,在母亲温暖关怀较少时与焦虑障碍并无显著相关。此外,rs6191-rs6196-rs41423247构成的单倍型GAG与低焦虑障碍风险显著关联,TGC与高焦虑障碍风险显著关联,且二者与母亲温暖关怀、母亲过度保护分别存在交互作用。未来可采用追踪研究,从表观遗传层面探讨教养方式与NR3C1影响焦虑障碍的内在机制。
Glucocorticoid receptor gene (NR3C1), one of the key genes involved in the HPA axis regulation, has been evidenced to have a role in various stress-related physical and mental illnesses. Previous studies concerning NR3C1 polymorphisms and anxiety disorders, however, have mostly been conducted among adult samples and looked into negative environmental variables such as adverse or traumatic life events while examining the gene-environment interactions. There is a dearth of knowledge on how NR3C1 polymorphisms could contribute to adolescent anxiety disorders. The purpose of this study was to examine the genetic variants in NR3C1 and their interaction with paternal and maternal parenting styles in relationship to adolescent anxiety disorders using a Chinese sample. This study adopted a case-control design. Of 3501 adolescents underwent a stepwise clinical screening, 117 who were diagnosed with anxiety disorders (74 females; average age 16.69 ~ 1.13 years) and 121 healthy controls (56 female; average age 16.54 ~ 1.05 years) were included in this study. Participants' oral mucosal samples were collected for DNA extraction and three single-nucleotide polymorphisms (SNPs) of the NR3C1 gene (i.e., rs41423247, rs6191, rs6196) were genotyped using MassARRAY system. The Chinese version of Parental Bonding Instrument was used to measure four types of paternal/maternal parenting styles (i.e., warmth, autonomy, overprotection, indifference). Multivariate logistic regressions were performed to examine the main effects of genotypes and parental/maternal parenting styles and their interactions in predicting the presence of anxiety disorders. Results revealed that rs6191 GG genotype, rs6196 AA genotype and rs41423247 GG genotype were associated with decreased risk of anxiety disorders. Higher level of paternal/maternal overprotection and indifference, as well as lower level of paternal warmth, could predict increased risk of anxiety disorders. Moreover, there was a significant interaction between rs4142324