Serotonin and serotonin transporter gene variant in rotating shift workers.
OBJECTIVE
Because serotonin (5-HT) is a neurotransmitter associated with circadian rhythm regulation, we explored a possible relation among 5-HT, serotonin metabolite, 5-hydroxyindolacetic acid (5HIAA), and the functional polymorphism of the serotonin transporter gene (SLC6A4) promoter with rotating shift work.


METHODS
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); 5-HIAA content was also significantly (P = 0.00004) higher in day workers (11.40+/-0.82 pg/mg) than in 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 = 0.016) difference in genotype distribution between day workers LL: 126 (28.8%), LS: 202 (46.2%), and SS: 109 (24.9%), and rotating shift workers LL: 47 (19.1%), LS: 124 (50.4%), and SS: 75 (30.5%). When we divided the subjects between workers with less and more than 60 month rotating shift-work exposure, the difference in SLC6A4 genotypes frequency was only significant in the group with > or =60 months (P = 0.011). In addition, 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).


CONCLUSIONS
Platelet 5-HT and 5-HIAA contents were significantly lower in rotating shift workers than 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 comorbidities and behavioral problems in rotating shift workers.
Sookoian
Silvia
S
Cardiologia Molecular Instituto de Investigaciones Medicas, A. Lanari. Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina.
Gemma
Carolina
C
Gianotti
Tomas Fernández
TF
Burgueño
Adriana
A
Alvarez
Azucena
A
González
Claudio Daniel
CD
Pirola
Carlos Jose
CJ
D000328:Adult; D000483:Alleles; D001786:Blood Glucose / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D002872:Chromosome Deletion; D002940:Circadian Rhythm / Q000235:genetics / Q000502:physiology; D005838:Genotype; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000097:blood*; D007328:Insulin / Q000097:blood; D008297:Male; D016254:Mutagenesis, Insertional / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012701:Serotonin / Q000097:blood*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D020178:Sleep Disorders, Circadian Rhythm / Q000097:blood / Q000235:genetics*; D014280:Triglycerides / Q000097:blood; D014940:Work Schedule Tolerance
D001786:Blood Glucose; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D007328:Insulin; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D014280:Triglycerides; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D002784:Cholesterol
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