SLEEP 2011 Abstract Supplement

A. Basic Science II. Cell and Molecular Biology and Genetics
whether these genetic findings can be replicated using total sleep period
measured by EEG in the Wisconsin Sleep Cohort (WSC).
Methods: We assess 1,876 polysomnographs (PSGs) in 1,300 adult individuals
from the WSC. Sleep onset is defined as the first occurrence
of stage 1 sleep, and sleep cessation is the final epoch of sleep prior to
morning awakening. Six hundred and sixty-nine individuals had more
than two PSGs separated by 4 years, so we could assess the reliability of
the EEG total sleep period within an individual over time. Genotyping
in this cohort was performed using Affymetrix 6.0 genechip and direct
Taqman genotyping. Bonferroni corrected genetic association is determined
using an additive genetic model and linear regression with subject
age, sex, BMI, and medications as potential covariates.
Results: We report whether variations in candidate genes are associated
with sleep duration. This includes known polymorphisms in ABCC9/
SUR2, COMT, HLA DQB1*0602, PER3, PER2, PER1 and CLOCK,
DEC2, MYRIP, OR10K1/2 and TSHZ2.
Conclusion: Results reveal support for the genetic control of sleep duration
in humans. Further studies are needed to examine gene-gene and
gene-environment interactions on this basic sleep phenotype.
0050
THE CATECHOL-O-METHYLTRANSFERASE (COMT) GENE
RELATES TO RESPIRATORY AROUSALS IN CHILDREN
WITH DOWN SYNDROME
Rodriguez A, Breslin JH, Mason GM, Bootzin RR, Nadel L, Edgin JO
Psychology, University of Arizona, Tucson, AZ, USA
Introduction: In previous studies, the homozygous Val polymorphism
of the COMT (catechol-O-methyltransferase) gene, which is involved
in the degradation of dopamine and norepinephrine, has been associated
with poor sleep continuity in children with ADHD (Gruber et al, 2006).
Specifically, children with ADHD have been shown to have more snoring
and respiratory arousals than typically developing children (Goroya
et al., 2009). Children with Down syndrome (DS) have been shown to
have attention deficits (Clark & Wilson, 2003) as well as poor sleep,
including symptoms of obstructive sleep apnea (Ng et al., 2006). Our
goal was to examine the relationship between COMT and respiratory
arousals in children with DS.
Methods: Seventeen children with DS (age range: 7-18 years, mean
age= 11.79; 18 girls) participated in this study. Nocturnal sleep was
assessed with ambulatory in-home polysomnography (PSG). ADHD
symptoms were assessed with the Conners Parent Rating Scales (CPRS-
3), and the ADHD Probability Index Score was calculated. Gene data
were collected via saliva samples in Oragene DNA kits (DNA Genotek)
and the Val/Met polymorphism of the COMT gene was genotyped using
a Taqman assay with a polymerase chain reaction (PCR)-based method.
Results: Eighty-two percent of our sample (n = 14) met criteria for pediatric
obstructive sleep apnea (AHI > 1.5) and twenty-nine percent (n =
5) met criteria for ADHD. We found that there was a trend for children
who were Met allele carriers (n = 10) to have a lower respiratory arousal
index compared to children with the Val-Val genotype (n = 7) (F (1,15)
= 3.802, p = 0.07), but we did not find a difference in AHI between the
two groups.
Conclusion: These findings lend support to the idea that COMT is involved
in the regulation of sleep in Down syndrome.
Support (If Any): Down Syndrome Research and Treatment Foundation,
National Down Syndrome Society, Arizona Alzheimer’s Research
Consortium, University of Arizona Foundation, The Lejeune Foundation,
and the Emory Biomarker Service Center
0051
OBSTRUCTIVE SLEEP APNEA AND ADIPOSE TISSUE GENE
EXPRESSION
Hayes AL 1 , Patel SR 2
1
Frances Payne Bolton School of Nursing, Case Western Reserve
University, Cleveland, OH, USA, 2 Division of Sleep Medicine,
Brigham and Women’s Hospital, Boston, MA, USA
Introduction: Obstructive sleep apnea (OSA) is associated with increased
levels of circulating inflammatory markers and a state of insulin
resistance. The tissues responsible for these effects are unclear. We hypothesized
that OSA may induce a pro-inflammatory and insulin resistant
state in adipose tissue.
Methods: 18 patients scheduled to undergo ventral hernia repair surgery
were recruited. Subjects wore a portable sleep monitor two nights
prior to surgery. The respiratory disturbance index (RDI) was obtained
across both nights and averaged. Biopsies from abdominal subcutaneous
and visceral fat depots were obtained intra-operatively. RNA was
isolated using a commercial kit. Expression of a set of 8 genes related
to inflammation and insulin resistance were measured using real time
PCR, normalizing for amount of the 18S component of ribosomal RNA.
Expression levels were compared between those with and without OSA
as defined by an RDI > 5.
Results: The OSA group (n=10) had a mean RDI of 19.2 ± 25.9 versus
0.6 ± 0.5 in the control group (n=8). Groups had similar age (56.1 ± 10.8
y versus 54.5 ± 12.2 y; p=0.8) and body mass index (36.1 ± 9.3 kg/m2
versus 35.2 ± 5.6 kg/m2; p=0.8). In subcutaneous fat, mean expression
levels of TNF-α, MCP-1, and IL-8 were 56%, 76%, and 95% greater in
those with OSA though none met criteria for statistical significance. In
visceral fat, PAI-1 expression was 3.1 fold greater in OSA though again,
this was not statistically significant (p=0.4). In contrast, adiponectin expression
was 54% less (p=0.0005) and PPAR-gamma expression was
31% less (p=0.05) in the visceral fat of those with OSA.
Conclusion: Decreased expression of adiponectin and PPAR-gamma in
visceral adipose tissue of apneics may provide a mechanism by which
insulin resistance may occur. A trend towards greater inflammation was
observed in subcutaneous fat, though the differences were not statistically
significant.
Support (If Any): This work was supported by NIH HL081385,
CA116867, and the ATS.
0052
POLYMORPHISMS OF THE MACROPHAGE MIGRATION
INHIBITORY FACTOR (MIF) GENE IN CHILDREN WITH
AND WITHOUT OBSTRUCTIVE SLEEP APNEA (OSA)
Khalyfa A, Gozal LK, Bhattacharjee R, Sans-Capdevila O, Gozal D
Pediatrics, University of Chicago, Chicago, IL, USA
Introduction: OSA is currently viewed as a systemic inflammatory
disorder. Furthermore, it has become apparent that genetic and environmental
factors modulate the occurrence and magnitude of morbid
consequences in pediatric OSA. MIF is a potent pro-inflammatory cytokine
and a key modulator of immune, inflammatory responses, and is associated
with cardiovascular disease. This study compares the frequency
of 28 nucleotide polymorphisms (SNPs) in the MIF gene of children
with OSA and matched controls.
Methods: Children (ages 5-10 years) prospectively underwent a standard
overnight multichannel polysomnographic evaluation and a fasting
morning blood draw. The diagnostic criteria for OSA were an obstructive
AHI ≥2/h TST, snoring during the night, and a nadir oxyhemoglobin
saturation