Common functional polymorphisms in SLC6A4 and COMT genes are associated with circadian phenotypes in a South American sample

The molecular study of circadian rhythms in humans could be an excellent approach to understand the relation between genes and behavior. It is possible that variations in genes involved in neurotransmission and/or synaptic plasticity, such as catechol- O -methyltransferase ( COMT ) and serotonin transporter ( SLC6A4 ) could be of particular interest in understanding human circadian phenotypes. The aim of this study is to analyze the possible and novel associations of the functional polymorphisms in COMT and SLC6A4 genes (Val158Met and 5 - HTTLPR ) and circadian phenotypes in healthy Colombian subjects. 191 university students were genotyped for two functional polymorphisms in COMT and SLC6A4 genes (rs4680 and rs4795541). We applied two scales to measure phenotypic patterns of human circadian rhythms: Composite Scale of Morningness (CSM) and Epworth Sleepiness Scale (ESS). We found a significant association between 5 - HTTLPR polymorphism and morning preference score (CSM) ( p = 0.027) using an overdominant genotypic model and association of COMT Val158Met with daytime sleepiness (ESS scores) ( p = 0.038) in a genotypic recessive model. These results were supported by differences in genotype frequencies between circadian typologies for SLC6A4 gene ( p = 0.007) and categories of diurnal sleepiness for COMT gene ( p = 0.032). Our results suggest, for the first time, a significant relationship between functional SLC6A4 and COMT polymorphisms with specific human circadian phenotypes: morning preference and diurnal sleepiness. These results need to be replicated in other populations. Further study of functional polymorphisms in other synaptic genes could be of relevance for the identification of novel candidate genes for circadian phenotypes, and related endophenotypes of neuropsychiatric importance, in healthy humans.