Association of P10L Polymorphism in Melanopsin Gene with Chronic Insomnia in Mexicans.

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 ˃ 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.

Genetic contribution in primary sleep disorders / Contribución genética en los trastornos primarios del sueño

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.

Mutational analysis of the GLA gene in Mexican families with Fabry disease.

Fabry disease (FD) is a lysosomal storage disorder, which develops due to a deficiency in the hydrolytic enzyme, α-galactosidase A (α-Gal A). Alpha-Gal A hydrolyzes glycosphingolipid globotriaosylceramide (Gb3), and an α-Gal A deficiency leads to Gb3 accumulation in tissues and cells in the body. This pathology is likely to involve multiple systems, but it is generally considered to affect primarily vascular endothelium. In this study, we investigated mutations in the GLA gene, which encodes α-Gal A, in Mexican families with FD. We included seven probands with FD that carried known mutations. We analysed pedigrees of the probands, and performed molecular screening in 65 relatives with the potential of carrying a GLA mutation. Five mutations (P40S, IVS4+4, G328V, R363H, R404del) were detected in seven unrelated Mexican families with the classic FD phenotype. Of the 65 relatives examined, 42 (64.6%) had a GLA gene mutation. In summary, among seven Mexican probands with FD, 65 relatives were at risk of carrying a known GLA mutation, and molecular screening identified 42 individuals with the mutation. Thus, our findings showed that it is important to perform molecular analysis in families with FD to detect mutations and to provide accurate diagnoses for individuals that could be affected.