Serotonin and Serotonin Transporter Gene Variant in Rotating Shift Workers

Abstract

Study Objectives: Because serotonin is a neurotransmitter associated with circadian rhythm regulation, we explored a possible relationship of serotonin (5-HT), serotonin metabolite, 5-hydroxyindolacetic acid (5-HIAA), and the functional polymorphism of the serotonin transporter gene (SLC6A4) promoter with rotating shift work. Design & Participants: 683 men were included in this study: 437 day-workers were compared with 246 rotating shift-workers. Results: Platelet 5-HT content differed significantly (p=0.002) between day-workers (41.28±1.99 pg/mg) and rotating shift-workers (37.91±4.16 pg/mg). Accordingly, 5-HIAA content was also significantly (p=0.00004) higher in day-workers (11.40±0.82 pg/mg) in comparison with rotating shift-workers (9.33±1.02 pg/mg). We looked for further differences in SLC6A4 promoter (5-HTTLPR, 44 bp insertion: long (L)/deletion: short (S) alleles). We found a significant (p< 0.008) difference in genotypes distribution between day-workers (LL: 126, LS: 202, and SS: 109 individuals) and rotating shift-workers (LL: 47, LS: 124 and SS: 75 individuals). Logistic regression analysis showed that rotating shift work was associated with S allele independently of work time exposure (Estimate±SE: 0.27±0.11, p<0.015). Besides, there was a significantly lower content of platelet 5-HIAA in S allele carriers in comparison with the other genotypes (SS: 9.2±1.0 pg/mg vs. SL/LL: 11.0±0.8 pg/mg, p<0.02). In conclusion, platelet 5-HT and 5-HIAA contents were significantly lower in rotating shift-workers in comparison with day-workers and there was a significant association between the S variant of SLC6A4 promoter and shift work. These findings may be important for targeting effective therapeutic strategies to ameliorate the associated co- morbidities and behavioral problems in rotating shift workers.