Influence of fasting during the night shift on next day eating behavior, hunger, and glucose and insulin levels: a randomized, three-condition, crossover trial.

AIMS: To investigate the influence of fasting during the night shift on eating behavior, hunger, glucose and insulin levels the following day. METHODS: Study with 10 male police officers who have been working at night. Participants were tested under three different conditions separated by at least 6 days of washout in a randomized, crossover design: "Night Shift Fasting" (NSF)-two nights of fasting during the night shift; "Night Shift Eating" (NSE)-two nights with the consumption of a standardized meal during the night shift (678 ± 42 kcal consumed at ~ 0200 h); and "Nighttime Sleep" (NS)-two nights of sleep. The morning after, blood glucose and insulin and hunger ratings were assessed, and food intake was assessed with an ad libitum test meal. Food intake was also assessed throughout the remainder of the day using a food record. Generalized Estimating Equations were used to analyze the effect of experimental condition. RESULTS: Food intake during the test meal, especially of proteins and fats, was higher after fasting during the night shift compared to the other conditions (p < 0.05), whereas desire to eat scores were lower after the NSF compared to NSE condition (p = 0.043). Hunger levels were lower after the NSF compared to the NS condition (p = 0.012). Insulin and HOMA-IR were also lower in the morning after NSF (p < 0.001). CONCLUSION: Fasting during the night shift leads to not only a higher intake of energy and macronutrients both in the early morning after work and throughout the next day, but also lower insulin levels and HOMA-IR in the morning. REGISTRATION NUMBER OF CLINICAL TRIAL: NCT03800732. Initial release: 01/09/2019. Last release: 02/23/2022.

Early chronotype with advanced activity rhythms and dim light melatonin onset in a rural population.

Studying communities at different stages of urbanisation and industrialisation can teach us how timing and intensity of light affect the circadian clock under real-life conditions. We have previously described a strong tendency towards morningness in the Baependi Heart Study, located in a small rural town in Brazil. Here, we tested the hypothesis that this morningness tendency is associated with early circadian phase based on objective measurements (as determined by dim light melatonin onset, DLMO, and activity) and light exposure. We also analysed how well the previously collected chronotype questionnaire data were able to predict these DLMO values. The average DLMO observed in 73 participants (40 female) was 20:03 ± 01:21, SD, with an earlier average onset in men (19:38 ± 01:16) than in women (20:24 ± 01:21; P ≤ .01). However, men presented larger phase angle between DLMO and sleep onset time as measured by actigraphy (4.11 hours vs 3.16 hours; P ≤ .01). Correlational analysis indicated associations between light exposure, activity rhythms and DLMO, such that early DLMO was observed in participants with higher exposure to light, higher activity and earlier light exposure. The strongest significant predictor of DLMO was morningness-eveningness questionnaire (MEQ) (beta=-0.35, P ≤ .05), followed by age (beta = -0.47, P ≤ .01). Sex, light exposure and variables derived from the Munich chronotype questionnaire were not significant predictors. Our observations demonstrate that both early sleep patterns and earlier circadian phase have been retained in this small rural town in spite of availability of electrification, in contrast to metropolitan postindustrial areas.

Self-reported discomfort associated with Daylight Saving Time in Brazilian tropical and subtropical zones.

BACKGROUND: Daylight Saving Time (DST) annually moves clocks 1 hour forward, when daytime is longer than night. Previous studies from medium and high latitude locations have pointed to a disruptive effect of DST on human circadian rhythms. Since Brazil is an equatorial country implementing DST, a different relationship between photic and social synchronisers may interfere with DST effects. AIM: To explore the prevalence and duration of self-reported discomfort related to DST among Brazilian residents (latitude 12-33° S, longditude 39-57° W). It was hypothesised that an elevated prevalence of self-reported discomfort would be found in Brazil, due to the pronounced uncoupling between social and geophysical synchronisers. SUBJECTS AND METHODS: In total, 12 467 volunteers completed a web-based, Brazilian version of Horne-Östberg Morningness-Eveningness Questionnaire, provided demographic information, and answered questions related to DST complaints (discomfort, duration of discomfort). RESULTS: Of the total sample, 45.43% reported no discomfort related to DST, with meaningful proportions for all chronotypes. However, eveningness was most associated with discomfort. About one fourth of the total sample reported discomfort over the whole DST period. Gender interaction is largely supported by these results. CONCLUSIONS: DST at low latitude locations may be disruptive for circadian rhythms, since seasonality of sunrise near the equator is negligible or very mild.

Detecting chronotype differences associated to latitude: a comparison between Horne--Östberg and Munich Chronotype questionnaires.

BACKGROUND: Chronotype, phase preference to perform activities during a 24-hour day, represents distinct circadian temporal organization of living organisms. Morning and evening types can be identified by questionnaires such as Horne and Östberg (HO) and Munich Chronotype Questionnaire (MCTQ). Environmental factors, such as different light-dark cycles experienced at different latitudes, interact with the organisms' circadian timekeeping system. Therefore, chronotype is expected to vary as a result of different geographical locations. AIM: To identify differences in chronotype distribution in populations of two Brazilian cities, Natal and Sao Paulo, located at different latitudes. SUBJECTS AND METHODS: Two specific questionnaires, the Horne and Östberg Questionnaire (HO) and the Munich Chronotype Questionnaire (MCTQ), were used to identify chronotypes of undergraduate students from São Paulo and Natal. RESULTS: The comparison of the curve distributions of HO and MCTQ scores between both cities allowed one to observe that, while HO curves of São Paulo and Natal overlapped, MCTQ curves showed a clear shift towards eveningness in São Paulo. CONCLUSION: This experiment confirmed results from previous studies that the farther away from the equator, the longer the delay of the sleep phase. It was also concluded that MCTQ is better at detecting this phenomenon.

Does the transition into daylight saving time really cause partial sleep deprivation?

AIM: To identify possible changes in the sleep patterns according to chronotype in undergraduate students during the daylight saving time (DST) transition. METHODS: A total of 378 students answered the Morningness-Eveningness Questionnaire (MEQ) to determine their chronotype and kept a diary about sleep-wake schedules 1 week before and after the DST transition. Oral mucosal cell samples were collected for genetic analysis. RESULTS: After the DST transition, intermediate types (I-types) delayed bedtime and increased their time in bed and all groups delayed their wake-up time. All groups presented a shorter phase angle between sunset and the bedtime after the DST transition. On the other hand, only E-types showed a tendency to reduce the phase angle between sunrise and wake-up time, while I-types and M-types kept the same phase angles between sunrise and wake-up time after the DST transition. The polymorphisms in the human genes CLOCK and PER3 were not associated with individual differences in sleep patterns, nor were they associated with an adjustment to the DST transition. CONCLUSION: Under the new set of social times determined by DST, the adjustment was only partial. I-types delayed bedtime and all groups delayed their wake-up times after the beginning of DST. Consequently, the time in bed after the DST transition was not reduced; Morning (M-types) and Evening-types (E-types) kept the same time in bed and I-types showed an increase on it.

Hemodialysis-induced chronodisruption and chronotype distribution in patients with chronic kidney disease.

Changes in circadian rhythms have been observed in patients with chronic kidney disease (CKD), and evidence suggests that these changes can have a negative impact on health. This study aimed to investigate the existence of hemodialysis-induced chronodisruption, the chronotype distribution, and their association with sleep quality and quality of life (QoL). This was a cross-sectional study that enrolled 165 patients (mean age: 51.1 ± 12.5 y, 60.6% male) undergoing hemodialysis from three local units. The following instruments were used: the Morning-Eveningness Questionnaire (MEQ); a modified version of the Munich Chronotype Questionnaire (MCQT) to estimate hemodialysis-induced chronodisruption (HIC); the Kidney Disease QoL Short Form (KDQOL-SF); the Epworth Sleepiness Scale (ESS); the Pittsburgh Sleep Quality Index (PSQI) and the 10-Cognitive Screener (10-CS). HIC was present in 40.6% of CKD patients. Morning chronotype was prevalent in CKD patients (69%) compared to evening-type (17.1%) and significantly different from a paired sample from the general population (p < 0.001). HIC and chronotype were associated with different domains of QoL but not with sleep quality. This study suggests that there is a HIC and that morning chronotype is associated with CKD patients undergoing hemodialysis, with implications for QoL.

Actigraphic characterization of sleep and circadian phenotypes of PER3 gene VNTR genotypes.

The molecular circadian timing system involves genes known as "clock genes," such as the PER3 gene. Studies have demonstrated associations among a repeat polymorphism (VNTR) of the PER3 gene with chronotypes, with the occurrence of circadian rhythm disorders and with sleep homeostasis phenotypes. The aim of this study was to investigate, by actigraphy, sleep and circadian rhythm profiles of people with different genotypes for the VNTR polymorphism of the PER3 gene. We genotyped 467 individuals (46,39% male) for the PER3 VNTR polymorphism. The mean age of the participants was 21.84 ± 2.64, ranging from 18 to 30 y old. Actigraphy data were collected from a subsample of 81 subjects with PER3 4-repeats homozygous (PER34/4) or 5-repeats homozygous (PER35/5) genotypes from April to June of 2021. From this sample, 48 PER34/4 and 33 PER35/5 subjects wore a wrist actigraph between 12 and 19 d. The sleep onset (weekdays, p = 0.015; weekend, p = 0.022) and offset (weekdays, p = 0.004; weekend, p = 0.041) of the PER35/5 group occurred later than the PER34/4 group. Similar results were observed for the mid-sleep phase of weekdays (MSW) (p = 0.008) and free days (MSF) (p = 0.019), and for the mid-sleep phase corrected for sleep debt accumulated over the week (MSFsc) (p = 0.024). Despite the phase differences found between the PER34/4 and PER35/5 groups, no differences were found in sleep duration and social jet lag. However, the PER34/4 group presented, on average, a longer sleep rebound on the days off when compared to the PER35/5 (p = 0.002). The PER35/5 group showed lower interdaily stability (IS) (p = 0.032) and higher daily activity rhythm variability (IV) (p = 0.035). The findings of the present study revealed associations between the PER3 gene, sleep, and circadian rhythms. In general, we found that the gene is associated with the expression of sleep timing and duration and to the phase of the activity rhythm. The experiments carried out here occurred in the COVID-19 pandemic scenario, which should be considered as an environmental element with potential effects on the results obtained.

Multiple positive outcomes of a later school starting time for adolescents.

OBJECTIVE: We tested the effect of later school start time (LSST) by 1 hour during 1 week on sleep, sleepiness, and mood profile using within-subject design. DESIGN: A within-subject 3-weeks-long interventional study. A baseline week with school starting at 7:30 AM (week A), followed by an intervention week with school starting at 8:30 AM (week B), and a recovery week with school start time back to 7:30 AM (week C). Mixed model for repeated measures analysis was applied to test for the LSST effect between weeks. SETTING: A private high school with high level of socioeconomic status. PARTICIPANTS: Forty-eight adolescents from 3 different high school years. MEASUREMENTS: Participants were invited to wear actigraphs continuously during the 3 experimental weeks. Somnolence was obtained every school day twice, at arrival and before departure of school. Sleep quality and mood profile were evaluated by standard measures by the end of each school week, resulting in 3 repeated measures for each variable. RESULTS: Thirty-eight adolescents completed the study. Adolescents woke up later during week B (7:42 ± 00:30) in comparison to weeks A (6:54 ± 00:12) and C (6:46 ± 00:15) (p < .001), with no significant change on sleep onset between weeks (p = .657), resulting in a longer sleep duration in week B (p < .001). Significant improvements on sleepiness and mood profile were also reported during week B. CONCLUSIONS: Starting school later was effective in improving multiple aspects from sleep patterns, subjective sleepiness, and mood profile.

What are we measuring with the morningness-eveningness questionnaire? Exploratory factor analysis across four samples from two countries.

Individual variability in diurnal preference or chronotype is commonly assessed with self-report scales such as the widely used morningness-eveningness questionnaire (MEQ). We sought to investigate the MEQ's internal consistency by applying exploratory factor analysis (EFA) to determine the number of underlying latent factors in four different adult samples, two each from the United Kingdom and Brazil (total N = 3,457). We focused on factors that were apparent in all samples, irrespective of particular sociocultural diversity and geographical characteristics, so as to show a common core reproducible structure across samples. Results showed a three-factor solution with acceptable to good model fit indexes in all studied populations. Twelve of the 19 MEQ items in the three-correlated factor solution loaded onto the same factors across the four samples. This shows that the scale measures three distinguishable, yet correlated constructs: (1) items related to how people feel in the morning, which we termed efficiency of dissipation of sleep pressure (recovery process) (items 1, 3, 4, 5, 7, 9, 13, and 19); (2) items related to how people feel before sleep, which we called sensitivity to buildup of sleep pressure (items 2, 10, and 12); and (3) peak time of cognitive arousal (item 11). Although the third factor was not regarded as consistent since only one item was common among all samples, it might represent subjective amplitude. These results suggested that the latent constructs of the MEQ reflect dissociable homeostatic processes in addition to a less consistent propensity for cognitive arousal at different times of the day. By analyzing answers to MEQ items that compose these latent factors, it may be possible to extract further knowledge of factors that affect morningness-eveningness.

Compared Heritability of Chronotype Instruments in a Single Population Sample.

It is well established that the oldest chronotype questionnaire, the morningness-eveningness questionnaire (MEQ), has significant heritability, and several associations have been reported between MEQ score and polymorphisms in candidate clock genes, a number of them reproducibly across populations. By contrast, there are no reports of heritability and genetic associations for the Munich chronotype questionnaire (MCTQ). Recent genome-wide association studies (GWAS) from large cohorts have reported multiple associations with chronotype as assessed by a single self-evaluation question. We have taken advantage of the availability of data from all these instruments from a single sample of 597 participants from the Brazilian Baependi Heart Study. The family-based design of the cohort allowed us to calculate the heritability (h2) for these measures. Heritability values for the best-fitted models were 0.37 for MEQ, 0.32 for MCTQ, and 0.28 for single-question chronotype (MEQ Question 19). We also calculated the heritability for the two major factors recently derived from MEQ, "Dissipation of sleep pressure" (0.32) and "Build-up of sleep pressure" (0.28). This first heritability comparison of the major chronotype instruments in current use provides the first quantification of the genetic component of MCTQ score, supporting its future use in genetic analysis. Our findings also suggest that the single chronotype question that has been used for large GWAS analyses captures a larger proportion of the dimensions of chronotype than previously thought.

A single nucleotide polymorphism in the HOMER1 gene is associated with sleep latency and theta power in sleep electroencephalogram.

Glutamate is the most excitatory neurotransmitter in the central nervous system and it is involved in the initiation and maintaining of waking and rapid-eye-movement (REM) sleep. Homer proteins act in the trafficking and/or clustering of metabotropic glutamate receptors, and polymorphisms in the HOMER1 gene have been associated with phenotypes related to glutamate signaling dysregulation. In this study, we report the association of a single nucleotide polymorphism (SNP) in the HOMER1 gene (rs3822568) with specific aspects of sleep in a sample of the Brazilian population. To accomplish this, 1,042 individuals were subjected to a full-night polysomnography, and a subset of 983 subjects had rs3822568 genotyping data available. When compared with the A allele carriers, GG genotyped individuals showed higher sleep latency, lower sleep efficiency, reduced number of arousals per hour, lower apnea-hypopnea index (AHI) and lower theta spectral power. In summary, the present findings suggest that the rs3822568 polymorphism in the HOMER1 gene is associated with sleep EEG profiles and might have an impact on sleep quality and sleep structure, with potential to explain inter-individual variation in sleep homeostasis.

Association between light exposure and metabolic syndrome in a rural Brazilian town.

CONTEXT: Metabolic syndrome (MetS) is a complex condition comprising a 'clustering' of components representing cardiometabolic risk factors for heart disease and diabetes; its prevalence rate is high and consequences serious. Evidence suggests that light exposure patterns and misalignment of circadian rhythms might contribute to MetS etiology by impacting energy metabolism and glucose regulation. OBJECTIVE: We hypothesised that individuals with MetS would show disrupted circadian and sleep parameters alongside differences in light exposure profiles. We investigated this using data from a cohort study in Brazil. METHODS: Data from 103 individuals from the Baependi Heart Cohort Study aged between 50 and 70 were analysed. Motor activity and light exposure were measured using wrist-worn actigraphy devices. Cardiometabolic data were used to calculate the number of MetS components present in each participant, and participants grouped as MetS/non-MetS according to standard guidelines. Between-group comparisons were made for the actigraphy measures; additionally, correlation analyses were conducted. RESULTS: Motor activity and circadian profiles showed no differences between groups. However, the MetS group presented lower light exposure during the day and higher light exposure at night. Correlation analyses, including all participants, showed that greater daytime light exposure and greater light exposure difference between day and night were associated with reduced MetS risk (a lower number of MetS components). Also, the light exposure difference between day and night correlated with body mass index across all participants. CONCLUSIONS: The observed results suggest a direct association between light exposure and MetS which appears to not be attributable to disruptions in circadian activity rhythm nor to sleep parameters. This link between light exposure patterns and MetS risk could inform possible prevention strategies.

[Timekeeping molecules: implications for circadian phenotypes]. / Moléculas que marcam o tempo: implicações para os fenótipos circadianos.

OBJECTIVE: The aim of this study was to review the molecular chronobiology studies in the last 36 years in order Eto point out the advances in this area to health professionals. METHOD: We searched in the PubMed and Scopus data banks for articles related with human molecular chronobiology. The keywords used were 'clock genes, circadian rhythms, diurnal preference, delayed sleep phase syndrome, advanced sleep phase syndrome, photoperiod and mood disorder'. DISCUSSION: The knowledge about molecular mechanism of circadian rhythms increased a lot in the last years and now we are able to better understand the details of molecular processes involved in circadian and sleep regulation. Studies show that polymorphisms in clock genes are associated with sleep and mood disorders. These studies will be helpful to further elucidate the regulation of molecular mechanisms of circadian rhythms. CONCLUSIONS: The development of these studies in molecular chronobiology can be helpful to treat circadian and mood disorders and to prevent health risks caused by intercontinental flights (Jet Lag), nocturnal or shift work schedule.

Delayed Sleep in Winter Related to Natural Daylight Exposure among Arctic Day Workers.

Natural daylight exposures in arctic regions vary substantially across seasons. Negative consequences have been observed in self-reports of sleep and daytime functions during the winter but have rarely been studied in detail. The focus of the present study set out to investigate sleep seasonality among indoor workers using objective and subjective measures. Sleep seasonality among daytime office workers (n = 32) in Kiruna (Sweden, 67.86° N, 20.23° E) was studied by comparing the same group of workers in a winter and summer week, including work and days off at the weekend, using actigraphs (motion loggers) and subjective ratings of alertness and mood. Actigraph analyses showed delayed sleep onset of 39 min in winter compared to the corresponding summer week (p < 0.0001) and shorter weekly sleep duration by 12 min (p = 0.0154). A delay of mid-sleep was present in winter at workdays (25 min, p < 0.0001) and more strongly delayed during days off (46 min, p < 0.0001). Sleepiness levels were higher in winter compared to summer (p < 0.05). Increased morning light exposure was associated with earlier mid-sleep (p < 0.001), while increased evening light exposure was associated with delay (p < 0.01). This study confirms earlier work that suggests that lack of natural daylight delays the sleep/wake cycle in a group of indoor workers, despite having access to electric lighting. Photic stimuli resulted in a general advanced sleep/wake rhythm during summer and increased alertness levels.

PER3 variable number tandem repeat (VNTR) polymorphism modulates the circadian variation of the descending pain modulatory system in healthy subjects.

We evaluated the circadian pattern of variation of the descending pain modulatory system (DPMS) using a conditioned pain modulation (CPM) paradigm according to the variable-number tandem-repeat (VNTR) of the clock gene PER3 polymorphism. We assessed the relationship between the genotypes PER34/4 and PER35/5 and the temporal pattern of variation across the day using the following measures: the heat pain threshold (HPT), the cold pressure test (CPT), and the serum levels of BDNF and S100-B protein. The ∆-values (from afternoon to morning) of these measures were used for the analysis. The circadian phenotype was according to the mid-point sleep time established by the Munich ChronoType Questionnaire (MCTQ). We included 18 healthy volunteers (15 women) ages 18 to 30. A Generalized Linear Model (GLM) revealed a significant difference in the ∆-CPM-task between Per34/4 and Per35/5 genotypes, with means (SDs) of -0.41 (0.78) vs. 0.67 (0.90) (χ2 = 7.256; df = 1' P = 0.007), respectively. Both sleep deprivation of at least 2 h/day (B = -0.96, 95% confidence interval (CI) = -1.86 to -0.11)) and the ∆-S100-B protein (-0.03, 95% CI = -0.06 to -0.02) were negatively correlated with the ∆-CPM-task, while the ∆-BDNF was positively correlated with the ∆-CPM-task (0.015, 95% CI = 0.01 to 0.03). We observed a difference in the ∆-CPT between PER34/4 and PER35/5 (0.11 (4.51) vs. 4.00 (2.60), respectively) (χ2 = 22.251; df = 1 P = 0.001). These findings suggest that the polymorphism of PER35/5 is associated with a decrease in the inhibitory function of the DPMS over the course of the day. However, sleep deprivation is an independent factor that also reduces the inhibitory function of the DPMS, regardless of the PER3 VNTR polymorphism.

Simple detection of large InDeLS by DHPLC: the ACE gene as a model.

Insertion-deletion polymorphism (InDeL) is the second most frequent type of genetic variation in the human genome. For the detection of large InDeLs, researchers usually resort to either PCR gel analysis or RFLP, but these are time consuming and dependent on human interpretation. Therefore, a more efficient method for genotyping this kind of genetic variation is needed. In this report, we describe a method that can detect large InDeLs by DHPLC (denaturating high-performance liquid chromatography) using the angiotensin-converting enzyme (ACE) gene I/D polymorphism as a model. The InDeL targeted in this study is characterized by a 288 bp Alu element insertion (I). We used DHPLC at nondenaturating conditions to analyze the PCR product with a flow through the chromatographic column under two different gradients based on the differences between D and I sequences. The analysis described is quick and easy, making this technique a suitable and efficient means for DHPLC users to screen InDeLs in genetic epidemiological studies.

Casein kinase I epsilon (CKIvarepsilon) N408 allele is very rare in the Brazilian population and is not involved in susceptibility to circadian rhythm sleep disorders.

Circadian rhythms are regulated by clock proteins through post-translational modifications. Indeed, Casein kinase I epsilon (CKIvarepsilon) promotes reversible phosphorylation of PER proteins, and a deficiency in this phosphorylation has been implicated in human sleep disorders. Here, we investigated the CKIvarepsilon S408N polymorphism in a Brazilian population sample. The N408 allele was previously described to be much less frequent in individuals with Delayed Sleep-Phase Syndrome (DSPS), than in the general Japanese population, suggesting a protective function for the allele against the disease. We found that this polymorphism is very rare in the Brazilian population (1.37%), indicating that it has no influence on susceptibility to circadian rhythm sleep disorders. Therefore, it is necessary to account for adaptative influences in genetic background, analyzing different groups with different photoperiods, to validate the effects of this and other polymorphisms on sleep and circadian disorders.

PER3 gene regulation of sleep-wake behavior as a function of latitude.

OBJECTIVES: We searched for interactions between PER3 gene VNTR polymorphism, latitude, sleep duration, diurnal sleepiness, and social jetlag. DESIGN: We selected samples from 3 distinct cities along the latitudinal range of Brazil and comprising the same time zone. SETTING: Undergraduate universities located in 3 major cities of Brazil. PARTICIPANTS: A total of 980 undergraduate students: 276 from Maceio (latitude 9°), 358 from Campinas (latitude 22°), and 346 from Porto Alegre (latitude 30°). MEASUREMENTS: PER3 variable number of tandem repeats genotyping, diurnal sleepiness, sleep duration (weekdays and weekend), chronotype, and social jetlag. RESULTS: Latitude is associated with a differential expression of circadian and sleep profiles. We observed a shift toward eveningness with increased latitude and increased social jetlag and diurnal sleepiness at latitude 30°. Moreover, our results suggest that the PER3 variable number of tandem repeats polymorphism has a modulatory effect on these circadian and sleep profiles: the variant PER34/4 is associated with a smaller difference in the sleep duration on weekdays among different latitudes and is associated with longer sleep duration on weekends just at latitude 30°, even when compared to both other genotypes at the same latitude. On the other hand, irrespective of the genotype, volunteers from latitude 30° expressed increased social jetlag and diurnal sleepiness. CONCLUSIONS: The seasonal variation in the light/dark cycle, tied to latitude, together with the tight social time constraints that young adults are subjected to during weekdays, generates differences in the sleep phenotypes. Volunteers with the PER34/4 variant who live farther from the equator have a greater increase in their weekend sleep duration.

HLA-DQB1 genotyping in a family with narcolepsy-cataplexy.

Narcolepsy is a unique model for dysfunction in mechanisms that regulate sleep and wakefulness. The narcolepsy syndrome is characterized by excessive daytime sleepiness with recurrent episodes of irresistible sleep, cataplexy, hypnagogic and/or hypnopompic hallucinations and sleep paralysis. The current hypothesis for the etiology of narcolepsy is that it is an autoimmune disorder because of its strong association with the human leukocyte antigen (HLA) system. HLA-DQ alleles are not particularly mutated in narcoleptic patients but they directly influence susceptibility to the disease. DQB10602 homozygote carriers have a two to four times higher risk of developing the disease than heterozygote carriers. In the present study we report a rare multiplex familial case of narcolepsy-cataplexy and show the strong effect of the HLA-DQB10602 allele upon the disease phenotype. In the family studied herein, both the proband and his brother are severely affected and homozygous DQB10602, whereas their sister does not carry the allele and is not affected at all. These data corroborate previous findings proposing DQB10602 homozygous subjects to be far more susceptible to narcolepsy. Insights into the DQB10602 positive family that include homozygous subjects may prove to be an important asset in the investigation of genetic vs. environmental factors predisposing to narcolepsy.

Clock polymorphisms and circadian rhythms phenotypes in a sample of the Brazilian population.

A Clock polymorphism T to C situated in the 3' untranslated region (3'-UTR) has been associated with human diurnal preference. At first, Clock 3111C had been reported as a marker for evening preference. However these data are controversial, and data both corroborating and denying them have been reported. This study hypothesizes that differences in Clock genotypes could be observed if extreme morning-type subjects were compared with extreme evening-type subjects, and the T3111C and T257G polymorphisms were studied. The possible relationship between both polymorphisms and delayed sleep phase syndrome (DSPS) was also investigated. An interesting and almost complete linkage disequilibrium between the polymorphisms T257G in the 5' UTR region and the T3111C in the 3' UTR region of the Clock gene is described. Almost always, a G in position 257 corresponds to a C in position 3111, and a T in position 257 corresponds to a T in position 3111. The possibility of an interaction of these two regions in the Clock messenger RNA structure that could affect gene expression was analyzed using computer software. The analyses did not reveal an interaction between those two regions, and it is unlikely that this full allele correspondence affects Clock gene expression. These results show that there is no association between either polymorphism T3111C or T257G in the Clock gene with diurnal preference or delayed sleep phase syndrome (DSPS). These controversial data could result from the possible effects of latitude and clock genes interaction on circadian phenotypes.