scholarly journals Genetic Determinants of Neurobehavioral Responses to Caffeine Administration during Sleep Deprivation: A Randomized, Cross Over Study (NCT03859882)

Genes ◽  
2021 ◽  
Vol 12 (4) ◽  
pp. 555
Author(s):  
Mégane Erblang ◽  
Fabien Sauvet ◽  
Catherine Drogou ◽  
Michaël Quiquempoix ◽  
Pascal Van Beers ◽  
...  
Keyword(s):  
Sleep Deprivation ◽  
Nucleotide Polymorphisms ◽  
Genetic Determinants ◽  
Placebo Condition ◽  
Double Blind ◽  
Single Nucleotide ◽  
Psychomotor Vigilance Test ◽  
Tnf Α ◽  
And Performance ◽  
Psychomotor Vigilance

This study investigated whether four single nucleotide polymorphisms (SNPs) moderated caffeine effects on vigilance and performance in a double-blind and crossover total sleep deprivation (TSD) protocol in 37 subjects. In caffeine (2 × 2.5 mg/kg/24 h) or placebo-controlled condition, subjects performed a psychomotor vigilance test (PVT) and reported sleepiness every six hours (Karolinska sleepiness scale (KSS)) during TSD. EEG was also analyzed during the 09:15 PVT. Carriers of the TNF-α SNP A allele appear to be more sensitive than homozygote G/G genotype to an attenuating effect of caffeine on PVT lapses during sleep deprivation only because they seem more degraded, but they do not perform better as a result. The A allele carriers of COMT were also more degraded and sensitive to caffeine than G/G genotype after 20 h of sleep deprivation, but not after 26 and 32 h. Regarding PVT reaction time, ADORA2A influences the TSD effect but not caffeine, and PER3 modulates only the caffeine effect. Higher EEG theta activity related to sleep deprivation was observed in mutated TNF-α, PER3, and COMT carriers, in the placebo condition particularly. In conclusion, there are genetic influences on neurobehavioral impairments related to TSD that appear to be attenuated by caffeine administration. (NCT03859882).

scholarly journals 0274 Associations of TNFα Gene Polymorphism with Resilience to Sleep Deprivation and Caffeine Sensitivity

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A104-A104
Author(s):  
L Skeiky ◽  
D A Hansen ◽  
B C Satterfield ◽  
M Petrovick ◽  
T J Balkin ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Information Processing ◽  
Sleep Deprivation ◽  
Signal To Noise Ratio ◽  
Placebo Condition ◽  
Double Blind ◽  
Psychomotor Vigilance Test ◽  
Recovery Sleep ◽  
Time In Bed ◽  
Official Policy

Abstract Introduction Sleep deprivation degrades the fidelity of human brain information processing, leading to cognitive impairment. Carriers of the A allele of a single nucleotide polymorphism of the TNFα gene (G308A, rs1800629) have been found to be resilient to cognitive impairment due to sleep deprivation as compared to individuals homozygous for the G allele. Caffeine mitigates the cognitive impairment associated with sleep deprivation. We investigated whether the effects of caffeine and TNFα genotype interact. Methods In an 18-day, controlled, in-laboratory study, 12 healthy adults (age 27.4±6.9; 6 females) underwent three sessions of 48-hour total sleep deprivation (TSD), with each TSD session preceded and followed by three nights of baseline and/or recovery sleep (10 hours time in bed). In randomized, counterbalanced, double-blind, placebo-controlled fashion, during each TSD session a specific dose of caffeine (0, 200, or 300 mg) was administered four times at 12-hour intervals. Vigilant attention was measured every 2 hours during each TSD session with a psychomotor vigilance test (PVT), for which the log of the signal-to-noise ratio (LSNR) derived from the RT distribution was determined as a measure of the fidelity of information processing. Each subject’s TNFα genotype was assessed from a blood sample. Results Subjects homozygous for the TNFα G allele showed greater PVT impairment during sleep deprivation in the 0 mg caffeine (i.e., placebo) condition as compared to carriers of the A allele and as compared to the 200 and 300 mg caffeine conditions (mixed-effects ANOVA, genotype by dose interaction: F2,566=5.23, p=0.005). There was no appreciable caffeine-related difference in performance for carriers of the A allele, who were relatively resilient to TSD regardless of caffeine dose. Conclusion These results suggest non-additive, interacting effects of TNFα genotype and caffeine and a potentially shared mechanism of action with regard to the fidelity of information processing during sleep deprivation. Support This research was supported by ONR. AJB, TJB, VFC, RHR were supported by DoD MOMRP-USAMRDC. The views expressed here are those of the authors and do not represent the official policy or position of the DoD.

scholarly journals Genetics and Cognitive Vulnerability to Sleep Deprivation in Healthy Subjects: Interaction of ADORA2A, TNF-α and COMT Polymorphisms

Life ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1110
Author(s):  
Mégane Erblang ◽  
Catherine Drogou ◽  
Danielle Gomez-Merino ◽  
Arnaud Rabat ◽  
Mathias Guillard ◽  
...  
Keyword(s):  
Sleep Deprivation ◽  
Genetic Polymorphisms ◽  
Healthy Subjects ◽  
Receptor Gene ◽  
Cognitive Responses ◽  
Total Sleep Deprivation ◽  
Psychomotor Vigilance Test ◽  
Tnf Α ◽  
Vigilance Test ◽  
Psychomotor Vigilance

Several genetic polymorphisms differentiate between healthy individuals who are more cognitively vulnerable or resistant during total sleep deprivation (TSD). Common metrics of cognitive functioning for classifying vulnerable and resilient individuals include the Psychomotor Vigilance Test (PVT), Go/noGo executive inhibition task, and subjective daytime sleepiness. We evaluated the influence of 14 single-nucleotide polymorphisms (SNPs) on cognitive responses during total sleep deprivation (continuous wakefulness for 38 h) in 47 healthy subjects (age 37.0 ± 1.1 years). SNPs selected after a literature review included SNPs of the adenosine-A2A receptor gene (including the most studied rs5751876), pro-inflammatory cytokines (TNF-α, IL1-β, IL-6), catechol-O-methyl-transferase (COMT), and PER3. Subjects performed a psychomotor vigilance test (PVT) and a Go/noGo-inhibition task, and completed the Karolinska Sleepiness Scale (KSS) every 6 h during TSD. For PVT lapses (reaction time >500 ms), an interaction between SNP and SDT (p < 0.05) was observed for ADORA2A (rs5751862 and rs2236624) and TNF-α (rs1800629). During TSD, carriers of the A allele for ADORA2A (rs5751862) and TNF-α were significantly more impaired for cognitive responses than their respective ancestral G/G genotypes. Carriers of the ancestral G/G genotype of ADORA2A rs5751862 were found to be very similar to the most resilient subjects for PVT lapses and Go/noGo commission errors. Carriers of the ancestral G/G genotype of COMT were close to the most vulnerable subjects. ADORA2A (rs5751862) was significantly associated with COMT (rs4680) (p = 0.001). In conclusion, we show that genetic polymorphisms in ADORA2A (rs5751862), TNF-α (rs1800629), and COMT (rs4680) are involved in creating profiles of high vulnerability or high resilience to sleep deprivation. (NCT03859882).

scholarly journals Nonsynonymous single nucleotide polymorphisms of NHE3 differentially decrease NHE3 transporter activity

2015 ◽  
Vol 308 (9) ◽  
pp. C758-C766 ◽  
Author(s):  
Xinjun Cindy Zhu ◽  
Rafiquel Sarker ◽  
John R. Horton ◽  
Molee Chakraborty ◽  
Tian-E Chen ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Large Fraction ◽  
Regulatory Protein ◽  
Nucleotide Polymorphisms ◽  
Genetic Determinants ◽  
Single Nucleotide ◽  
Mutant Proteins ◽  
Homologous Protein ◽  
Genetic Abnormalities ◽  
The Impact

Genetic determinants appear to play a role in susceptibility to chronic diarrhea, but the genetic abnormalities involved have only been identified in a few conditions. The Na+/H+ exchanger 3 (NHE3) accounts for a large fraction of physiologic intestinal Na+ absorption. It is highly regulated through effects on its intracellular COOH-terminal regulatory domain. The impact of genetic variation in the NHE3 gene, such as single nucleotide polymorphisms (SNPs), on transporter activity remains unexplored. From a total of 458 SNPs identified in the entire NHE3 gene, we identified three nonsynonymous mutations (R474Q, V567M, and R799C), which were all in the protein's intracellular COOH-terminal domain. Here we evaluated whether these SNPs affect NHE3 activity by expressing them in a mammalian cell line that is null for all plasma membrane NHEs. These variants significantly reduced basal NHE3 transporter activity through a reduction in intrinsic NHE3 function in variant R474Q, abnormal trafficking in variant V567M, or defects in both intrinsic NHE3 function and trafficking in variant R799C. In addition, variants NHE3 R474Q and R799C failed to respond to acute dexamethasone stimulation, suggesting cells with these mutant proteins might be defective in NHE3 function during postprandial stimulation and perhaps under stressful conditions. Finally, variant R474Q was shown to exhibit an aberrant interaction with calcineurin B homologous protein (CHP), an NHE3 regulatory protein required for basal NHE3 activity. Taken together, these results demonstrate decreased transport activity in three SNPs of NHE3 and provide mechanistic insight into how these SNPs impact NHE3 function.

scholarly journals Association Between Apical Periodontitis and TNF-α -308 G>A Gene Polymorphism: A Systematic Review and Meta-Analysis

2017 ◽  
Vol 28 (5) ◽  
pp. 535-542 ◽  
Author(s):  
Alessandro Guimarães Salles ◽  
Lívia Azeredo Alves Antunes ◽  
Patrícia Arriaga Carvalho ◽  
Erika Calvano Küchler ◽  
Leonardo Santos Antunes
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Apical Periodontitis ◽  
Permanent Teeth ◽  
Genotype Distribution ◽  
Nucleotide Polymorphisms ◽  
Eligibility Criteria ◽  
Single Nucleotide ◽  
Mesh Terms ◽  
Tnf Α

Abstract Currently, investigations have focused on the identification of Single Nucleotide Polymorphisms (SNP) involved in host response and its ability to generate an immunity deficiency. The aim of this study was to perform a systematic review (SR) and meta-analysis to evaluate the association between TNF-α -308 G>A polymorphism and apical periodontitis (AP) phenotypes. A broad search for studies was conducted. The following databases were used: PubMed, Scopus, Web of Science, and VHL (Medline, SciELO, Ibecs, and Lilacs). The MeSH terms “Periapical Periodontitis,” “Periapical Abscess,” “Polymorphism, Genetic,” and “Polymorphism, Single Nucleotide” were used. MeSH synonyms, related terms, and free terms were included. Clinical investigations of individuals with different AP phenotypes in permanent teeth were selected. After application of the eligibility criteria, selected studies were qualified by assessing their methodological quality. A fixed effect model was used for the meta-analysis. The initial search identified 71 references. After excluding duplicate abstracts, 33 were selected. From these, two were eligible for quality assessment and were classified as being of moderate evidence. The included studies did not demonstrate association between AP and TNF-α -308 G>A SNP. However, the meta-analysis demonstrated an association between the genotype distribution and AP phenotype (OR= 0.49; confidence interval= 0.25, 0.96; p=0.04). The role of TNF-α -308 G>A SNP in AP phenotypes is debatable. Further studies are needed to confirm and understand the underlying mechanisms of the identified association.

scholarly journals INFLUENCE ON HOMEOSTASIS AS THE CRITERION FOR SELECTING SINGLE NUCLEOTIDE POLYMORPHISMS FOR THE STUDY OF METABOLIC SYNDROM IN THE KAZAKH POPULATION

REPORTS ◽  
2020 ◽  
Vol 5 (333) ◽  
pp. 86-93
Author(s):  
V.V. Benberin ◽  
◽  
T.A. Voshchenkova ◽  
A.A. Nagymtayeva ◽  
A.S. Sibagatova ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Traditional Approach ◽  
Population Based ◽  
Malignant Neoplasms ◽  
Nucleotide Polymorphisms ◽  
Genetic Determinants ◽  
Single Nucleotide ◽  
Sequence Of Events ◽  
Kazakh Population ◽  
Symptom Complex

Metabolic syndrome (MS) is increasingly cited as the world's leading health risk. The sequence of events toward multimorbidity in most cases passes through MS. According to the research, MS heritability ranges from 23 to 27% in Europeans, and 51 to 60% in Asians. The purpose of the review: to form a strategy for the selection of single nucleotide polymorphisms (SNPs) for the study of MS in the Kazakh population based on the effect of SNPs on homeostasis indicators The stable symptom complex of MS is a complicated dynamic system of successive accumulations of dysmetabolic disorders of homeostasis. This system starts the development of subsequent age-associated diseases), such as cardiometabolic, neurodegenerative, and malignant neoplasms. The system for selecting SNPs for the MS study, proposed on the basis of the concept of homeostasis dysfunction, assumes, in conditions of limited resources, to see the greatest level of their influence within the conditional framework of three genetic models of homeostasis dysregulation: insulin resistance , oxidative stress, and chronic inflammation. This approach is fundamentally different from the traditional approach involving candidate genes. It is expected that scientific research in this direction will contribute not only to the understanding of general biological processes, but also to the targeted search for genetic determinants and for new opportunities for personalized interventions.

The G allele in IL-10-1082 G/A may have a role in lowering the susceptibility to panic disorder in female patients

2016 ◽  
Vol 28 (6) ◽  
pp. 357-361 ◽  
Author(s):  
Han-Joon Kim ◽  
Yong-Ku Kim
Keyword(s):  
Panic Disorder ◽  
Patient Group ◽  
Control Group ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Female Patients ◽  
Immune System Activation ◽  
Tnf Α ◽  
System Activation ◽  
And Control

BackgroundImmune system activation is involved in the pathophysiology of panic disorder (PD). We investigated INF-γ+874 A/T, TNF-α-308 G/A, and IL-10-1082 G/A single nucleotide polymorphisms (SNPs) to determine their association with PD.MethodThis study enroled 135 PD patients and 135 healthy controls. INF-γ+874 A/T (rs2430561), TNF-α-308 G/A (rs1800629), and IL-10-1082 G/A (rs1800896) were genotyped.ResultsThere were no differences in genotypes or allele frequencies between the patient and control groups, regardless of accompanying agoraphobia. However, for female patients, the G allele frequency in IL-10 SNP was higher in the control group than in the patient group. Additionally, the female control group had a higher frequency of the A/G and G/G genotype in the IL-10 SNP than the female patient group.ConclusionWe suggest that the G allele in IL-10-1082 G/A might have a role in reducing the manifestations of PD in female patients. Further studies are needed to extend and confirm our findings.

Association of RETN and TNFRSF1B polymorphisms with TNF-α inhibitor response in rheumatoid arthritis patients

2020 ◽  
Author(s):  
Nga Thi Trinh ◽  
Hyun Jeong Kim ◽  
Woorim Kim ◽  
Sang Oh Kang ◽  
Kyung Hyun Min ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Statistical Significance ◽  
Univariate Analysis ◽  
Multivariable Logistic Regression Analysis ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Final Model ◽  
Asian Populations ◽  
Tnf Α

Abstract Background: Despite the improvement from the introduction of tumor necrosis factor inhibitors (TNFi) in the rheumatoid arthritis (RA), TNFi therapy fails for more than 30% or results in a partial response. Thus, we aimed to explore treatment marker by examining the association of single nucleotide polymorphisms (SNPs) with response to TNFi therapy.Method: Genes associated with RA or RA treatment were reviewed and fourteen SNPs with minor allele frequency ≥ 20% in the East Asian populations were selected and analyzed. Data were collected from 105 RA patients. Our primary endpoint was the disease activity score using 28-joint count after six months of treatment (DAS28-6month). The secondary outcomes were the subcomponents of DAS28.Results: A total of 88 patients were included in the final analyses. Among the 14 SNPs analyzed, one SNP showed statistical significance in DAS28-6month: patients with the GG allele of RETN rs1862513 had a 4.7 times higher chance of low disease activity at 6-months than GC or CC-carriers (p = 0.033), as indicated by multivariable logistic regression analysis. Rs3397 was marginally significant in univariate analysis (p=0.059), but was significant in the multivariable model (p=0.041). The final model explained 24.5% (Nagelkerke R2) of the variance in DAS28-6month.Conclusion: Our results demonstrated that, among the genes related to RA, SNPs in RETN and TNFRSF1B were associated with the response of TNFi treatment.

scholarly journals The Effects of an Energy Drink on Psychomotor Vigilance in Trained Individuals

2019 ◽  
Vol 4 (3) ◽  
pp. 47 ◽  
Author(s):  
Antonio ◽  
Kenyon ◽  
Horn ◽  
Jiannine ◽  
Carson ◽  
...  
Keyword(s):  
Reaction Time ◽  
Fixed Time ◽  
Energy Drink ◽  
Time Frame ◽  
Caffeine Intake ◽  
Test Reaction ◽  
Double Blind ◽  
Psychomotor Vigilance Test ◽  
Vigilance Test ◽  
Psychomotor Vigilance

The psychomotor vigilance test (PVT) measures one’s behavioral alertness. It is a visual test that involves measuring the speed at which a person reacts to visual stimuli over a fixed time frame (e.g., 5 min). The purpose of this study was to assess the effects of an energy drink on psychomotor vigilance as well as a simple measure of muscular endurance (i.e., push-ups). A total of 20 exercise-trained men (n = 11) and women (n = 9) (mean SD: age 32 7 years; height 169 10 cm; weight; 74.5 14.5 kg; percent body fat 20.3 6.2%; years of training 14 9; daily caffeine intake 463 510 mg) volunteered for this randomized, double-blind, placebo-controlled, crossover trial. In a randomized counterbalanced order, they consumed either the energy drink (ED) (product: BANG®, Weston Florida) or a similar tasting placebo drink (PL). In the second visit after a 1-week washout period, they consumed the alternate drink. A full 30 minutes post-consumption, they performed the following tests in this order: a 5-minute psychomotor vigilance test, three sets of push-ups, followed once more by a 5-minute psychomotor vigilance test. Reaction time was recorded. For the psychomotor vigilance test, lapses, false starts and efficiency score are also assessed. There were no differences between groups for the number of push-ups that were performed or the number of false starts during the psychomotor vigilance test. However, the ED treatment resulted in a significantly lower (i.e., faster) psychomotor vigilance mean reaction time compared to the PL (p = 0.0220) (ED 473.8 42.0 milliseconds, PL 482.4 54.0 milliseconds). There was a trend for the ED to lower the number of lapses (i.e., reaction time > 500 milliseconds) (p = 0.0608). The acute consumption of a commercially available ED produced a significant improvement in psychomotor vigilance in exercise-trained men and women.

Single nucleotide polymorphisms in piRNA-pathway genes: an insight into genetic determinants of human diseases

2019 ◽  
Vol 295 (1) ◽  
pp. 1-12 ◽  
Author(s):  
Jyoti Roy ◽  
Kalyani Anand ◽  
Swati Mohapatra ◽  
Rojalin Nayak ◽  
Trisha Chattopadhyay ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Human Diseases ◽  
Nucleotide Polymorphisms ◽  
Genetic Determinants ◽  
Single Nucleotide ◽  
Pirna Pathway ◽  
Insight Into

scholarly journals Functional Inflammatory Genotypes in Ischemic Stroke: Could We Use Them to Predict Age of Onset and Long-Term Outcome?

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Stella Marousi ◽  
Anna Antonacopoulou ◽  
Haralambos Kalofonos ◽  
Panagiotis Papathanasopoulos ◽  
Marina Karakantza ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Cox Regression ◽  
Age Of Onset ◽  
Adverse Outcome ◽  
Nucleotide Polymorphisms ◽  
Term Outcome ◽  
Single Nucleotide ◽  
Long Term Outcome ◽  
Tnf Α

Functional single-nucleotide polymorphisms (SNPs) of inflammatory cytokines have been previously related to the occurrence of an ischemic stroke (IS). We investigated whether five functional SNPs (i.e., TNF-α-308G>A, IL6-174G>C, IL12B 1188A>C, IL4-589C>T, and IL10-1082G>A) might be associated with the age of onset and 6-month outcome of an acute IS. A probe-free real-time PCR methodology was used to genotype 145 consecutively admitted cases with a first-ever IS. Simple Kaplan-Mayer and adjusted Cox regression analyses showed no association between inflammatory genotypes and the age of IS onset. IL6-174G>C, IL12B 1188A>C, IL4-589C>T, and IL10-1082G>A were not found to significantly contribute to the long-term outcome of the disease. However, carriage of the TNF-α-308 GG genotype was significantly associated with reduced odds for an adverse outcome. Larger studies are needed to confirm our results.

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