Sleep Flashcards
1
Q
AANAT
A
- High Impact Gene (Sleep Onset and Circadian Preferences)
- Rate limiting enzyme of melatonin synthesis
- Responsible for the circadian rhythm of melatonin production via light
- Variants responsible for delayed sleep onset
- Variants contribute to evening preferences
- Treat? Add Melatonin
2
Q
AANAT Alleles
A
- A allele is risk variant (later sleep onset)
- GG genotype is very common (ancestral)
- AG strongly associated with Delayed Sleep Phase Syndrome
- AA is very rare
3
Q
AANAT Micronutrient Deficiencies
A
- B-6
- Mag Glycinate and Mag Threonate
- Zinc
- Tryptophan (5-HTP)
- Folate
4
Q
ABCC9
A
- ATP-binding cassette, subfamily C member 9
- Provides information to make SUR2 protein
- SUR2 is principle protein of the cell potassium ion channel
- Unknown how this relates to sleep duration - genome studies show high phenotypic expression
- G allele = 30 minutes less sleep duration
5
Q
ADA
A
- Adenosine Deaminase
- Responsible for breaking down adenosine
- T allele = 35% lower levels adenosine deaminase = higher sleep pressure and sleep longer because not breaking down adenosine (TT or CT)
- Sleep deeper and more slow-wave sleep but very impacted by sleep deprivation
6
Q
ADA Supplementation Support
A
- Zinc
- Luteolin
- Caffeine
- Inosine (potent antioxidant)
- Berberine – be careful because it suppresses ADA even further
7
Q
ADORA2A (I Adora Caffeine)
A
- Adenosine A2A Receptor
- TT genotype = more sensitivity to caffeine effects on sleep
- TT genotype = greater anxiety with caffeine
- ADA and CYP1A2 must be considered before recommending guidelines for caffeine
8
Q
BDNF
A
- Stickler’s Fave Gene! Be sure to optimize!
- Brain-derived Neurotrophic Factor
- Important to memory, learning, and cognitive processing
- Supports survival of existing neurons and encourages growth and differentiation of new neurons and synapses
- T allele carriers had lower blood BDNF than CC
- CC has about 20 minutes more slow-wave sleep (Stage 3/4) and increased sleep intensity compared to CT
- CC has greater resilience/performance when sleep-deprived
9
Q
BDNF Interventions
A
- Holy Basil/Tulsi (Dan's fave) -- Ursolic Acid - boosts BDNF indirectly and increases growth hormone in muscle, causes DNA to produce FNDC% > Irosine This creates same response as exercise - DHA - Progesterone - Estrogen - Melatonin - DHEA - Quercetin - Caffeine - Curcumin - Niacin - Magnesium L-Threonate - Bacopa (Dan thinks everyone should be on this) - Inosine - Sunlight
10
Q
CLOCK gene
A
- Circadian Locomotor Output Cycles Kaput (What?)
- This CLOCK gene is core to circadian cycle
- Primarily a modifier - changing transcription rates or expression of other genes (turns things on or off)
11
Q
CLOCK(1) (SNP in CLOCK gene)
A
- Affects the persistence and period of Circadian rhythms
- GG = 8.5 hours average sleep
- A allele = 8 hours
12
Q
CLOCK(2) (SNP in CLOCK gene)
A
- Presence of G allele = favorable dietary profile for PUFAs when they sleep longer (need DHA)
- AA = 8-8.5 hours sleep
- GA = 8 hours
- GG = 7.5 hours
- Seems to have more impact than Clock(1)
13
Q
CLOCK(3) (SNP in CLOCK gene)
A
- GG Associated with evening preference, delayed sleep onset, shorter sleep times
- A allele (GA and AA) associated with more normal chronotypes
14
Q
COMT (Carrie’s fave)
A
- HIGH IMPACT - CROSSES ALL BORDERS - KNOW THIS
- Catechol-O-methyltransferase
V158M variant enzyme is COMT - The major enzymes of the metabolic degradation of catecholamines: dopamine and norepinephrine
- Also involved in detox including estrogens
- Relation to vit B-12
- A functional polymorphism (in exon region) val to met (creates change in enzyme itself) - replacement of amino acid
- GG = val/val
- GA = valine/methionine
- AA = met/met
- Three to four-fold reduction in enzyme activity compared with homozygosity for V158 (GG genotype)
15
Q
COMT AA (Worrier) = Slow degradation of catecholamines = high catecholamines (norepinephrine is more important than dopamine) - A is common; AA is more rare
A
- Most common = pain sensitivity, anxiety, insomnia
- Can also cause: Schizophrenia, aggression, violence, delirium, panic, tachycardia, high BP
16
Q
COMT GG (Warrior) = Fast degradation of catecholamines = low catecholamines
A
- Most common =
- Can also cause: Food cravings, addictions, substance abuse, anger, impulsivity, high-risk behavior
17
Q
COMT Sleep
A
- AA = 30 minutes less sleep + insomnia + disrupted sleep REM latency (time to REM onset) - AA: 93 minutes - GA: 74 minutes - GG: 67 minutes Waking minutes per night - AA: 71 minutes (important b/c need extra sleep time) - GA: 57 minutes - GG: 48 minutes Sleep onset latency - AA: 25 minutes - GA: 18 minutes - GG: 14 minutes
18
Q
COMT
A
- Look at hormones
- Modafinil doesn’t work on AAs
- Estrogen slows COMT and Testosterone speeds it
- All about balance
19
Q
GNB3
A
- G-protein-beta subunit 3
- codes for G proteins that regulate cellular response
- Fxnl polymorphism
- TTs have lower quality sleep and sleep longer than C’s
- ## T allele has greater response to Viagra!
20
Q
GRIA3
A
Sleep Duration Template
- Glutamate receptor, Ioniotropic, AMPA subunit
- Mediates excitatory transmission in the brain
- Glutamate is main excitatory neurotransmitter in brain
- AA = early morning waking (in females)
- CC = 7-8 hours and greater sleep disturbances and shorter sleep with age
- CA and AA = 8+ hours
21
Q
MTNR1B
A
- Melatonin receptor 1B
- Encodes for MT2 protein
- T allele (CT variant) = latency of 65 mins LONGER from sleep onset to REM sleep
- T allele = 13% lower melatonin duration – melatonin peaks later and ends sooner
22
Q
NPSR1
A
- Neuropeptide S Receptor 1
- Not sure how it works but plays role in arousal/wakefulness
- T allele leads to amino acid sub in binding site = 10x sensitivity due to change
- AA = Normal bedtime, normal duration
- AT = 15 min sleep delay
- TT = 30 min sleep delay
- T allele = shorter sleep duration
23
Q
PER2
A
- Core regulator of circadian system
- Related to heart clock
- correlates to heart attack highest risk in early morning
24
Q
PER2 (1)
A
- SNP in PER2 that regulates gene transcription
- G = extreme morning preference and Advanced Sleep Phase Syndrome
- G = Longer sleep duration (8+)
25
PER2 (2)
- PER2 coding region Functional SNP
- results in amino acid substitution of glycine for glutamine
- Don't know exactly what this creates but phenotypic response is early morn pref and ASPS and alert in morning
- Perhaps don't put them on Meditteranean diet if GG
26
PER3 (1)
- G allele = delayed sleep phase syndrome
| - Functional
27
PER3 (2)
- C = Morning Preference
- G = Prone to stay up late
- G = free running = WIll go to bed whenever - chornotype jumps around = full dysregulation
28
PPP2R4
- G = High association with hypersomnia in those without autoimmune
29
TNFa
- COMMON GENE/HIGH IMPACT
- Tumor necrosis factor alpha
- Major SNP for inflammation
- AA allele = Normal sleep but more apnea and chronic health conditions
- GA = Decreased sleep disturbances
- GG = Morning fatigue and more sleep disturbances
30
HLA DRB1
- Associated with vitamin D
- Increased autoimmunity (lupus and MS)
- T allele = 9x risk of narcolepsy vaccinated with H1N1 vaccine
31
TRCa
- T cell receptor
- Associated with Hypersomnia and Narcolepsy
- Can lead to greater SLEEP DURATION
