SLEEP

Szymusiak, Ronald S.

doi: 10.5665/sleep.3184pmid: N/A

Fraigne, Jimmy J.; Peever, John H.

doi: 10.5665/sleep.3186pmid: 24293745

Jones, Barbara E.; Hassani, Oum K.

doi: 10.5665/sleep.3188pmid: 24293746

McGinty, Dennis; Alam, Noor

doi: 10.5665/sleep.3190pmid: 24293747

Luppi, Pierre-Hervé; Peyron, Christelle; Fort, Patrice

doi: 10.5665/sleep.3192pmid: 24293748

Blouin, Ashley M.; Siegel, Jerome M.

doi: 10.5665/sleep.3194pmid: 24293749

Pelluru, Dheeraj; Konadhode, RodaRani; Shiromani, Priyattam J.

doi: 10.5665/sleep.3196pmid: 24293750

Jego, Sonia; Adamantidis, Antoine

doi: 10.5665/sleep.3198pmid: 24293751

Kim, Myeong-Kyu; Cho, Yong Won; Shin, Won Chul; Cho, Jae Wook; Shon, Young Min; Kim, Jee Hyun; Yang, Kwang Ik; Earley, Christopher J.; Allen, Richard P.

doi: 10.5665/sleep.3200pmid: 24293752

AbstractStudy Objectives:Recent genome-wide association studies (GWAS) for Caucasians identified several allelic variants associated with increased risk of developing restless legs syndrome (RLS), also known as Willis-Ekbom disease. Although the pathogenic mechanisms of RLS are not entirely understood, it is becoming increasingly evident that many diseases such as RLS can be attributed to an epistasis. The study objectives were to evaluate whether the associations of RLS with all loci determined in previous GWAS for Caucasians can be replicated significantly for the Korean population and to elucidate whether an epistasis plays a role in the pathogenesis of RLS.Design, Setting, and Participants:DNA from 320 patients with RLS and 320 age- and sex-matched controls were genotyped for variants in the RLS loci.Measurements and Results:A significant association was found for rs3923809 and rs9296249 in BTBD9 (P < 0.0001 and P = 0.001, respectively); the odds ratio (OR) for rs3923809 was 1.61 (P < 0.0001) to 1.88 (P < 0.0001) and the OR for rs9296249 was 1.44 (P = 0.001) to 1.73 (P = 0.002), according to the model of inheritance. The OR for the interaction between rs3923809 in BTBD9 and rs4626664 in PTPRD was 2.05 (P < 0.0001) in the additive model, 1.80 (P = 0.002) in the dominant model and 2.47 (P = 0.004) in the recessive model. There was no significant association between genotypes of all tested single nucleotide polymorphisms and the mean value of serum iron parameters.Conclusions:Our results suggest that the role of BTBD9 in the pathogenesis of restless legs syndrome is more universal across populations than previously reported and more efforts should be focused on the role of epistasis in the genetic architecture of restless legs syndrome.

Chowdhuri, Susmita; Bascom, Amy; Mohan, David; Diamond, Michael P.; Badr, M. Safwan

doi: 10.5665/sleep.3202pmid: 24293753

AbstractStudy Objectives:Gender differences in the prevalence of sleep apnea/hypopnea syndrome may be mediated via male sex hormones. Our objective was to determine the exact pathway for a testosterone-mediated increased propensity for central sleep apnea via blockade of the 5α-reductase pathway of testosterone conversion by finasteride.Design:Randomization to oral finasteride vs. sham, single-center study.Setting:Sleep research laboratory.Participants:Fourteen healthy young males without sleep apneaIntervention:Hypocapnia was induced via brief nasal noninvasive positive pressure ventilation during stable NREM sleep. Cessation of mechanical ventilation resulted in hypocapnic central apnea or hypopnea.Measurements and Results:The apnea threshold (AT) was defined as the end-tidal CO2 (PETCO2) that demarcated the central apnea closest to the eupneic PETCO2. The CO2 reserve was defined as the difference in PETCO2 between eupnea and AT. The apneic threshold and CO2 reserve were measured at baseline and repeated after at a minimum of 1 month. Administration of finasteride resulted in decreased serum dihydrotestosterone. In the finasteride group, the eupneic ventilatory parameters were unchanged; however, the AT was decreased (38.9 ± 0.6 mm Hg vs.37.7 ± 0.9 mm Hg, P = 0.02) and the CO2 reserve was increased (−2.5 ± 0.3 mm Hg vs. −3.8 ± 0.5 mm Hg, P = 0.003) at follow-up, with a significantly lower hypocapnic ventilatory response, thus indicating increased breathing stability during sleep. No significant changes were noted in the sham group on follow-up study.Conclusions:Inhibition of testosterone action via the 5α-reductase pathway may be effective in alleviating breathing instability during sleep, presenting an opportunity for novel therapy for central sleep apnea in selected populations.