ABSTRACT
The aim of this pilot study was to determine the association of the P10L (rs2675703) polymorphism of the OPN4 gene with chronic insomnia in uncertain etiology in a Mexican population. A case control study was performed including 98 healthy subjects and 29 individuals with chronic insomnia not related to mental disorders, medical condition, medication or substance abuse. Samples were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Genetic analyses showed that the T allele of P10L increased risk to chronic insomnia in a dominant model (p = 1 ×10-4; odds ratio (OR) = 9.37, CI = 8.18-335.66, Kelsey statistical power (KSP) = 99.9%), and in a recessive model (p = 7.5 × 10-5, OR = 9.37, KSP = 99.3%, CI = 2.7-34.29). In the insomnia group, we did not find a correlation between genotypes and chronotype (p = 0.219 Fisher's exact test), severity of chronic insomnia using ISI score (p = 0.082 Fisher's exact test) and ESS score (p Ë 0.999 Fisher's exact test). However, evening chronotype was correlated to daytime sleepiness severity, individuals with an eveningness chronotype had more severe drowsiness according to their insomnia severity index (ISI) score (p = 0.021 Fisher's exact test) and Epworth sleepiness scale (ESS) score (p = 0.015 Fisher's exact test) than the morningness and intermediate chronotype. We demonstrated that the T allele of the P10L polymorphism in the OPN4 gene is associated with chronic insomnia in Mexicans. We suggest the need to conduct larger studies in different ethnic populations to test the probable association and function of P10L and other SNPs in the OPN4 gene and in the onset of chronic insomnia.
Subject(s)
Sleep Initiation and Maintenance Disorders , Case-Control Studies , Humans , Pilot Projects , Rod Opsins , Sleep Initiation and Maintenance Disorders/geneticsABSTRACT
Sleep disorders are disturbances of sleep patterns, habits and sleep process, which can affect the onset stage, maintenance stage, or sleep-wake cycle. Sleep and sleep wake disorders are complex phenotypes regulated by various genes, environment, and interaction between them. Primary sleep disorders appear as a consequence of endogenous alterations in the mechanisms of the sleep-wake cycle, which are often aggravated by other factors. At present, genetic studies related to the molecular basis of sleep disorders are scarce, therefore, etiopathogenesis is uncertain. The aim of this review was to recognize the role of genetic factors in sleep disorders.
Los trastornos del sueño son alteraciones de los patrones, hábitos y proceso del dormir, en los cuales pueden estar afectadas las etapas de inicio, mantenimiento o bien el ciclo sueño-vigilia. El sueño y sus trastornos son fenotipos complejos regulados por varios genes, el ambiente y la interacción entre ambos. Los trastornos del sueño primarios aparecen como consecuencia de alteraciones endógenas en los mecanismos del ciclo sueño-vigilia, que a menudo se ven agravadas por diversos factores. En la actualidad son escasos los estudios genéticos relacionados con las bases moleculares de los trastornos del sueño, por lo tanto, su etiopatogenia es incierta. El propósito de esta revisión fue reconocer el papel de los factores genéticos en los trastornos del sueño.
Subject(s)
Gene-Environment Interaction , Genetic Predisposition to Disease , Sleep Wake Disorders/genetics , Genetic Markers , Humans , PhenotypeABSTRACT
Melanopsin is the most recent photopigment described. As all the other opsins, it attaches in the retina as chromophore. Its amino acid sequence resembles more invertebrate opsins than those of vertebrates. The signal transduction pathway of opsins in vertebrates is based on the coupling to the G protein transducin, triggering a signaling cascade that results in the hyperpolarization of the plasma membrane. On the contrary, the photoreceptors of invertebrates activate the Gq protein pathway, which leads to depolarizing responses. Phototransduction mediated by melanopsin leads to the depolarization of those cells where it is expressed, the intrinsically photosensitive retinal ganglion cells; the cellular messengers and the ion channel type(s) responsible for the cells´ response is still unclear. Studies to elucidate the signaling cascade of melanopsin in heterologous expression systems, in retina and isolated/cultured intrinsically photosensitive retinal ganglion cells, have provided evidence for the involvement of protein Gq and phospholipase C together with the likely participation of an ion channel member of the transient receptor potential-canonical family, a transduction pathway similar to invertebrate photopigments, particularly Drosophila melanogaster. The intrinsically photosensitive retinal ganglion cells are the sole source of retinal inferences to the suprachiasmatic nucleus; thus, clarifying completely the melanopsin signaling pathway will impact the chronobiology field, including the clinical aspects.
Subject(s)
Light Signal Transduction/physiology , Retinal Ganglion Cells/physiology , Rod Opsins/physiology , Animals , Drosophila melanogaster , GTP-Binding Protein alpha Subunits, Gq-G11/metabolism , Humans , Signal Transduction/physiologyABSTRACT
There are several factors that suggest serotonin [5-hydroxytryptamine (5-HT)] plays a role as a neurotransmitter/neuromodulator within the retina. The presence of mRNAs encoding 5-HT receptors (5-HTR) of the types 5-HT2CR and 5-HT5AR within the rat retina was investigated using in situ hybridization of digoxigenin-labeled probes. The 5HT5AR probe produced no labeling, whereas the 5HT2CR probe hybridized in cells scattered in the inner nuclear and ganglion cell layers. Thus, the 5HT2CR gene is expressed by retinal neurons, some of which represent third-order neurons, either amacrine or ganglion cells. This suggests that 5-HT may modulate the outgoing signal from the retina.