title: A length polymorphism in the circadian clock gene Per3 influences age at onset of bipolar disorder.
abstract: Age at onset of bipolar disorder might represent the penetrance of the system for specific genetic liability involved in the genesis of the illness. Genetic factors influencing age at onset have been shown to play a role in shaping core characteristics of the illness, such as severity and pattern of recurrence. Genetic variants of genes regulating the circadian clock could contribute to define endophenotypes of bipolar disorder, and have been associated with clinical features of the disease. The coding region of Per3 gene contains a variable-number tandem-repeat (VNTR) polymorphism which has been associated with diurnal preference, sleep structure and sleep homeostasis in healthy subjects. In a homogeneous sample of 99 patients affected by bipolar disorder type I we observed that Per3 VNTR influenced age at onset of illness: earlier age at onset in homozygote carriers of Per35 variant, later in homozygotes for Per34, and intermediate in heterozygotes. Allele frequencies were not significantly different from those reported in healthy subjects. Results need to be confirmed in larger samples, but warrant interest for the variants of molecular clock genes as possible endophenotypes of bipolar disorder.
authors.affiliation: Department of Clinical Neurosciences, Scientific Institute and University Vita-Salute San Raffaele, Milan, Italy. benedetti.francesco@hsr.it
authors.forename: Francesco
authors.initials: F
authors.lastname: Benedetti
authors.forename: Sara
authors.initials: S
authors.lastname: Dallaspezia
authors.forename: Cristina
authors.initials: C
authors.lastname: Colombo
authors.forename: Adele
authors.initials: A
authors.lastname: Pirovano
authors.forename: Elena
authors.initials: E
authors.lastname: Marino
authors.forename: Enrico
authors.initials: E
authors.lastname: Smeraldi
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000704:Analysis of Variance; D001714:Bipolar Disorder / Q000235:genetics*; D016009:Chi-Square Distribution; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D056950:Period Circadian Proteins; D011110:Polymorphism, Genetic; D014157:Transcription Factors / Q000235:genetics*; D055815:Young Adult
chemical_list: D009687:Nuclear Proteins; C512644:PER3 protein, human; D056950:Period Circadian Proteins; D014157:Transcription Factors