Disease relevance of PER3

• For instance, a point mutation in a human clock gene (Per2) was shown to produce the rare advanced sleep phase syndrome, whereas a functional polymorphism in Per3 is associated with the more frequent delayed sleep phase syndrome [1].
• In this study, we investigated the association between an exonic length variation in a circadian gene, Period3 (Per3), and breast cancer risk using blood samples collected from a recently completed breast cancer case-control study in Connecticut. There were 389 Caucasian cases and 432 Caucasian controls included in our analysis [2].

Psychiatry related information on PER3

• However, the trends for ARNTL and PER3 are suggestive of their involvement in bipolar disorder and warrant further study in a larger sample [3].
• The data show that this polymorphism in PER3 predicts individual differences in the sleep-loss-induced decrement in performance and that this differential susceptibility may be mediated by its effects on sleep homeostasis [4].

High impact information on PER3

• In situ hybridization observation revealed that light during the early subjective night [circadian time (CT) 13.5] or the late subjective night (CT20) caused an induction of Per1 and Per2 but not Per3 mRNA in the SCN [5].
• Deregulated expression of the PER1, PER2 and PER3 genes in breast cancers [6].
• Association of the length polymorphism in the human Per3 gene with the delayed sleep-phase syndrome: does latitude have an influence upon it [7]?
• We found that the variant Per3 genotype (heterozygous + homozygous 5-repeat alleles) was associated with an increased risk of breast cancer among premenopausal women (odds ratio, 1.7; 95% confidence interval, 1.0-3.0) [2].
• Gel retardation and methylation interference (MI) assays show that PER3 binds transcription factor Sp1 [8].

Biological context of PER3

• The most suggestive haplotypes in PER3 showed a Bonferroni-corrected P-value of PGC = 0.07 [3].
• Finally, by co-transfection of a Sp1-expressing plasmid, we show that Sp1 can stimulate transcription from a reporter gene containing the PER3 sequence [8].
• A biallelic variable number tandem repeat (VNTR) polymorphism exists in human PER3, consisting of 4 or 5 repeats of a 54-bp sequence in a region encoding a putative phosphorylation domain [9].
• Here, we investigate how such molecular oscillations are altered as a function of photoperiod by analyzing Period (Per1, Per2, and Per3) gene expression at the mRNA level using SCN tissue sections and in situ hybridization [10].

Other interactions of PER3

• Genetic variations within the human PER2 and PER3 genes have been linked with diurnal preference and disorders of sleep timing [11].

References