The Effect of Nicotine on HPA Axis Activity in Females is Modulated by the FKBP5 Genotype

Abstract

Tobacco smoking modulates activity in the hypothalamic-pituitary-adrenal (HPA) axis and is used to cope with stress, especially by females. The single nucleotide polymorphism (SNP) rs1360780, linked to FK506-binding protein 51 (FKBP5), has been shown to affect HPA axis functioning, and has thus been suggested as a promising candidate for indicating vulnerability to stress-related disorders. The aim of this study was to investigate the interaction between nicotine consumption and rs1360780 on cortisol plasma levels in females. A total of 296 female smokers (assessed by the Fagerström Test for Nicotine Dependence; FTND) were genotyped for the SNP rs1360780. We measured participants' cortisol plasma concentration in blood plasma collected 3 h after standardized tobacco smoking exposure. In the 36 TT-homozygotes, we found a significant negative correlation between the FTND sum score and cortisol plasma concentrations. Using linear regression analysis, we found that the FTND sum score accounted for 12.4% of the variance of cortisol plasma levels. This association was not detected in C-allele carriers. Our results suggest that nicotine is an important confounder in the modulation of HPA axis activity by FKBP5. In light of these findings, future studies on FKBP5 should seek to include data on nicotine consumption as a covariate.

The Interaction of Child Abuse and rs1360780 of the FKBP5 Gene is Associated with Amygdala Resting-State Functional Connectivity in Young Adults

“…The distribution of rs1360780 alleles did not deviate from the Hardy-Weinberg equilibrium (χ2 = 0.29, p = .59). As per Grabe et al (2016) and other studies on rs1360780 genotype (Koopmann et al, 2016), we combined the CC and CT carriers into one group, thus comparing T-homozygotes with C allele carriers.…”

Examining sex differences in pleiotropic effects for depression and smoking using polygenic and gene‐region aggregation techniques

“…For example, Rogausch, Kochen, Meineke, and Hennig (2007) found that G allele carriers at rs41423247 of NR3C1 were more likely to become smokers and had significantly higher daily cigarette consumption than C homozygotes. Other SNPs within NR3C2, FKBP5, and CRHR1 have also been examined in relation to smoking outcomes (dos Santos et al, 2012;Jensen et al, 2015;Koopmann et al, 2016;Rovaris et al, 2013;Tang et al, 2015), with mixed results. Interestingly, a small GWAS of daily cigarette use reported associations at SNPs within NR3C2, providing additional evidence that genes underlying HPA-axis function may also play a role in smoking behavior.…”

Chronic cocaine administration upregulates FKBP5 in the extended amygdala of male and female rats

“…Several studies have investigated drug use and FKBP5 genetic variability in humans. FKBP5 genotype is associated with the severity of withdrawal from nicotine (Jensen and Sofuoglu, 2016), as well as the effect of nicotine on the HPA axis (Koopmann et al, 2016). The interaction of early life trauma and FKBP5 genetic variation predicts heavy drinking in college students (Lieberman et al, 2016), and FKBP5 genetic variability is associated with severity of alcohol withdrawal (Huang et al, 2014).…”