Sookoian Silvia, Gemma Carolina, Gianotti Tomas Fernández, Burgueño Adriana, Alvarez Azucena, González Claudio Daniel, Pirola Carlos Jose
Cardiologia Molecular Instituto de Investigaciones Medicas, A. Lanari. Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina.
Sleep. 2007 Aug;30(8):1049-53. doi: 10.1093/sleep/30.8.1049.
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.
683 men were included in this study: 437 day workers were compared with 246 rotating shift workers.
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).
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.
由于血清素(5-羟色胺,5-HT)是一种与昼夜节律调节相关的神经递质,我们探讨了5-HT、血清素代谢产物5-羟吲哚乙酸(5HIAA)以及血清素转运体基因(SLC6A4)启动子的功能多态性与轮班工作之间的可能关系。
本研究纳入了683名男性:437名日班工人与246名轮班工人进行比较。
日班工人(41.28±1.99 pg/mg)和轮班工人(37.91±4.16 pg/mg)的血小板5-HT含量存在显著差异(P = 0.002);日班工人(11.40±0.82 pg/mg)的5-HIAA含量也显著高于轮班工人(9.33±1.02 pg/mg)(P = 0.00004)。我们进一步研究了SLC6A4启动子(5-HTTLPR,44 bp插入:长(L)/缺失:短(S)等位基因)的差异。我们发现日班工人(LL:126例(28.8%),LS:202例(46.2%),SS:109例(24.9%))和轮班工人(LL:47例(19.1%),LS:124例(50.4%),SS:75例(30.5%))的基因型分布存在显著差异(P = 0.016)。当我们将受试者分为轮班工作暴露时间少于60个月和多于60个月的两组时,SLC6A4基因型频率的差异仅在暴露时间≥60个月的组中显著(P = 0.011)。此外,与其他基因型相比,S等位基因携带者的血小板5-HIAA含量显著较低(SS:9.2±1.0 pg/mg vs. SL/LL:11.0±0.8 pg/mg,P <0.02)。
轮班工人的血小板5-HT和5-HIAA含量显著低于日班工人,且SLC6A4启动子的S变异与轮班工作之间存在显著关联。这些发现对于制定有效的治疗策略以改善轮班工人的相关合并症和行为问题可能具有重要意义。