Sookoian S et al. (2007) Serotonin and serotonin transporter gene variant in rotating shift workers. Sleep 30: 1049–1053

Desynchronization of circadian rhythms from environmental conditions can have important health implications for rotating shift workers (those who work shifts that rotate or change according to a set schedule). Those individuals have a high risk of developing cardiovascular and metabolic problems. Using a cohort of 683 Argentinian men of European ancestry (437 day workers, 246 rotating shift workers), Sookoian et al. have explored the relationships between 5-hydroxytryptamine (5-HT; a neurotransmitter with an important role in modulating circadian rhythms), 5-hydroxyindoleacetic acid (5-HIAA; a 5-HT metabolite), functional polymorphism of the 5-HT transporter gene (SLC6A4), and work schedule.

Platelet 5-HT and 5-HIAA content were both greater in day workers than in shift workers. Significantly decreased platelet 5-HIAA content, but not platelet 5-HT content, was observed in individuals homozygous for the SLC6A4 promoter short variant, relative to other genotypes. The short (deletion) variant of the SLC6A4 promoter reduces SLC6A4 transcription rates relative to the long (44 bp insertion) variant. Overall, SLC6A4 allele distribution differed between day workers and shift workers, with the short allele being more prevalent in shift workers. This difference was observed in individuals with at least 5 years' exposure to their present work schedule, but not in those with shorter exposure, indicating that individuals harboring short SLC6A4 variants (i.e. those with decreased serotonergic function) might better tolerate shift work than those with long variants.

The authors conclude that better understanding of the mechanisms underlying circadian rhythm desynchronization might aid the development of therapies to alleviate comorbidities associated with shift work.