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
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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
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3
Q

AANAT Micronutrient Deficiencies

A
  • B-6
  • Mag Glycinate and Mag Threonate
  • Zinc
  • Tryptophan (5-HTP)
  • Folate
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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
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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
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6
Q

ADA Supplementation Support

A
  • Zinc
  • Luteolin
  • Caffeine
  • Inosine (potent antioxidant)
    • Berberine – be careful because it suppresses ADA even further
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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
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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
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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
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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)
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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
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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)
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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
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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)
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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

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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
Q

PER2 (2)

A
  • 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
Q

PER3 (1)

A
  • G allele = delayed sleep phase syndrome

- Functional

27
Q

PER3 (2)

A
  • C = Morning Preference
  • G = Prone to stay up late
  • G = free running = WIll go to bed whenever - chornotype jumps around = full dysregulation
28
Q

PPP2R4

A
  • G = High association with hypersomnia in those without autoimmune
29
Q

TNFa

A
  • 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
Q

HLA DRB1

A
  • Associated with vitamin D
  • Increased autoimmunity (lupus and MS)
  • T allele = 9x risk of narcolepsy vaccinated with H1N1 vaccine
31
Q

TRCa

A
  • T cell receptor
  • Associated with Hypersomnia and Narcolepsy
  • Can lead to greater SLEEP DURATION