Association of structural polymorphisms in the human period3 gene with delayed sleep phase syndrome

Recent progress in biological clock research has facilitated genetic analys is of circadian rhythm sleep disorders, such as delayed sleep phase syndrom e (DSPS) and non-24-h sleep-wake syndrome (N-24). We analyzed the human per iod3 (hPer3) gene, one of the human homologs of the Drosophila clock-gene p eriod (Per), as a possible candidate for rhythm disorder susceptibility. Al l of the coding exons in the hPer3 gene were screened for polymorphisms by a PCR-based strategy using genomic DNA samples from sleep disorder patients and control subjects. We identified six sequence variations with amino aci d changes, of which five were common and predicted four haplotypes of the h Per3 gene. One of the haplotypes was significantly associated with DSPS (Bo nferroni's corrected P = 0.037; odds ratio = 7.79; 95% CI 1.59-38.3) in our study population. Our results suggest that structural polymorphisms in the hPer3 gene may be implicated in the pathogenesis of DSPS.