FK506 binding protein 51 is a modulator of the hypothalamic-pituitary-adrenal axis activity. Its function is modulated by the single nucleotide polymorphism rs 1360780. Females often use smoking to cope with stress. The aim of this study was to investigate if the influence of nicotine consumption on cortisol plasma levels is modified by the polymorphism of rs 1360780 in females.

Two hundred and ninety-six female smokers were genotyped for the SNP rs1360780 of FKBP5 protein. Cortisol plasma concentrations were measured in blood plasma drawn three hours after smoking. Severity of tobacco addiction was assessed based on the Fagerström Test for Nicotine Dependence (FTND).

Thirty-six participants were TT-homozygotes and 260 were C allele carriers. In TT homozygotes, we found a significant negative correlation between the FTND sum score and the cortisol plasma concentrations. In a linear regression analysis, the FTND sum score accounts for 12.4% of the variance of cortisol plasma levels. By contrast, we could not find such an association in C allele carriers.

Our results suggest that nicotine is an important confounder in the modulation of HPA axis activity by FKBP5. In the light of these findings, future studies on FKBP5 should include nicotine consumption as a confounder.

The authors have not supplied their declaration of competing interest.