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A PERIOD3 variable-number-tandem-repeat polymorphism modulates melatonin treatment response in Delayed Sleep-Wake Phase Disorder

Magee, Michelle, Sletten, Tracey L., Murray, Jade M., Gordon, Christopher J., Lovato, Nicole, Bartlett, Delwyn J., Kennaway, David J., Lockley, Steven W., Lack, Leon C., Grunstein, Ronald R. , Archer, Simon and Rajaratnam, Shantha M.W (2020) A PERIOD3 variable-number-tandem-repeat polymorphism modulates melatonin treatment response in Delayed Sleep-Wake Phase Disorder Journal of Pineal Research.

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We examined whether a polymorphism of the PERIOD3 gene (PER3; rs57875989) modulated the sleep promoting effects of melatonin in Delayed Sleep-Wake Phase Disorder (DSWPD). One hundred and four individuals (53 males; 29.4±10.0 years) with DSWPD and a delayed dim light melatonin onset (DLMO) collected buccal swabs for genotyping (PER34/4 n=43; PER3 5 allele [heterozygous and homozygous] n=60). Participants were randomised to placebo or 0.5mg melatonin taken 1 hour before desired bedtime (or ~ 1.45 h before DLMO), with sleep attempted at desired bedtime (4 weeks; 5-7 nights/week). We assessed sleep (diary and actigraphy), Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), Patient-Reported Outcomes Measurement Information System (PROMIS: Sleep Disturbance, Sleep-Related Impairment), Sheehan Disability Scale (SDS), and Patient- and Clinician-Global Improvement (PGI-C, CGI-C). Melatonin treatment response on actigraphic sleep onset time did not differ between genotypes. For PER34/4 carriers, self-reported sleep onset time was advanced by a larger amount and sleep onset latency (SOL) was shorter in melatonin-treated patients compared to those receiving placebo (P=0.008), while actigraphic sleep efficiency in the first third of the sleep episode (SE T1) did not differ. For PER3 5 carriers, actigraphic SOL and SE T1 showed a larger improvement with melatonin (P<0.001). Melatonin improved ISI (P=0.005), PROMIS Sleep Disturbance (P<0.001) and Sleep-Related Impairment (P=0.017), SDS (P=0.019), PGI-C (P=0.028), and CGI-C (P=0.016) in PER34/4 individuals only. Melatonin did not advance circadian phase. Overall, PER34/4 DSWPD patients have a greater response to melatonin treatment. PER3 genotyping may therefore improve DSWPD patient outcomes.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :
Magee, Michelle
Sletten, Tracey L.
Murray, Jade M.
Gordon, Christopher J.
Lovato, Nicole
Bartlett, Delwyn J.
Kennaway, David J.
Lockley, Steven W.
Lack, Leon C.
Grunstein, Ronald R.
Rajaratnam, Shantha M.W
Date : 9 July 2020
Funders : National Health and Medical Research Council, NHMRC Australasian Sleep Trials Network, Philips Respironics, NHMRC Practitioner and Senior Principal Research Fellowships
Grant Title : National Health and Medical Research Council
Uncontrolled Keywords : Melatonin; Delayed Sleep-Wake Phase Disorder; PERIOD3, Polymorphism, Variable Number Tandem Repeats, Circadian Rhythm Sleep Disorders.
Additional Information : Embargo OK Metadata Pending
Depositing User : James Marshall
Date Deposited : 16 Jul 2020 13:33
Last Modified : 16 Jul 2020 13:33

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