ABSTRACT
Anxiety sensitivity (AS) is characterised by the fear of anxiety-related symptoms and is a risk factor for the development of anxiety-related disorders. We examined whether genetic variation in three stress response genes, CRHR1, NR3C1, and FKBP5, interact with childhood trauma (CT) to predict AS in South African adolescents. Xhosa (n = 634) and Coloured (n = 317) students completed self-report measures of AS and CT, and a total of eighteen polymorphisms within CRHR1, NR3C1, and FKBP5 were genotyped. Differences in AS based on genetic variation and CT were analysed within population and gender groups using multiple linear regression. Associations were found between AS and FKBP5 rs9296158 (p = 0.025) and rs737054 (p = 0.045) in Coloured males. Analysis of gene x CT interactions indicated that NR3C1 rs190488 CC-genotype, NR3C1 rs10482605 G-allele addition, and FKBP5 rs3800373 C-allele addition protect against AS with increasing CT in Xhosa females (p = 0.009), Xhosa males (p = 0.036) and Coloured males (p = 0.049), respectively. We identified two different protective single nucleotide polymorphism (SNP) combinations in a four-SNP CRHR1 haplotype in Coloured males. An analysis of the interaction between CT and a six-SNP FKBP5 haplotype in Coloured males revealed both protective and risk allelic combinations. Our results provide evidence for the influence of both genetic variation in CRHR1, NR3C1 and FKBP5, as well as CT x SNP interactions, on AS in South African adolescents. This study reinforces the importance of examining the influence of gene-environment (G X E) interactions within gender and population groups.
Subject(s)
Anxiety/genetics , Gene-Environment Interaction , Hypothalamo-Hypophyseal System/metabolism , Pituitary-Adrenal System/metabolism , Adolescent , Adult , Alleles , Anxiety/physiopathology , Child , Female , Genotype , Humans , Male , Polymorphism, Single Nucleotide/genetics , Risk Factors , Sex Factors , South AfricaABSTRACT
OBJECTIVES: Anxiety sensitivity (AS) has predictive potential for the development of anxiety disorders. We investigated the role that gene-environment (G × E) interactions, focussing on childhood trauma (CT) and selected SLC6A4 variants, play in modulating levels of AS in a South African adolescent population. METHODS: All adolescents (n = 951) completed measures for AS and CT. Six SLC6A4 polymorphisms were genotyped. G × E influences on AS levels were assessed using multiple linear regression models. Relevant confounders were included in all analyses. RESULTS: Xhosa (n = 634) and Coloured (n = 317) participants were analysed independently of one another. The 5-HTTLPR-rs25531 L-G haplotype associated with reduced AS among Xhosa adolescents (P = 0.010). In addition, the rs1042173 CC-genotype protected against increased levels of AS in Xhosa participants who had experienced increased levels of CT (P = 0.038). Coloured males homozygous for the S-allele had significantly increased levels of AS compared to Coloured males with at least one L-allele (P = 0.016). CONCLUSIONS: This is the first study to be conducted on AS in adolescents from two ethnically diverse populations. Results indicate that the L-G haplotype confers protection against high AS levels in a Xhosa population. Furthermore, increased CT was found to protect against high levels of AS in Xhosa rs1042173 CC-carriers.
Subject(s)
Anxiety/genetics , Gene-Environment Interaction , Life Change Events , Polymorphism, Genetic , Serotonin Plasma Membrane Transport Proteins/genetics , Adolescent , Alleles , Anxiety/ethnology , Female , Genotype , Humans , Linear Models , Male , South Africa/ethnologyABSTRACT
BACKGROUND: We evaluated the role that selected variants in serotonin transporter (5-HTT), dopamine receptor 2 (DRD2) and brain-derived neurotrophic factor (BDNF) genes play in PTSD symptom severity in an at-risk population. We also investigated the interaction between the genetic variants to determine whether these variables and the interactions between the variables influenced the severity of PTSD symptoms. METHODS: PTSD symptoms were quantitatively assessed using the Davidson Trauma Scale (DTS) in 150 participants from an at-risk South African population. All participants were genotyped for the 5-HTTLPR, DRD2 Taq1A and BDNF Val66Met polymorphisms. Gene-gene interactions were investigated using various linear models. All analyses were adjusted for age, gender, major depressive disorder diagnosis, level of resilience, level of social support and alcohol dependence. RESULTS: A significant interaction effect between DRD2 Taq1A and BDNF Val66Met variants on DTS score was observed. On the background of the BDNF Val66Val genotype, DTS score increased significantly with the addition of a DRD2 Taq1A A1 allele. However, on the BDNF Met66 allele background, the addition of an A1 allele was found to reduce total DTS score. CONCLUSIONS: This study provides preliminary evidence for an epistatic interaction between BDNF Val66Met and DRD2 Taq1A polymorphisms on the severity of PTSD symptoms, where both too little and too much dopamine can result in increased PTSD symptom severity.
