title: Genetic variations of human neuropsin gene and psychiatric disorders: polymorphism screening and possible association with bipolar disorder and cognitive functions.
abstract: Human neuropsin (NP) (hNP) has been implicated in the progressive change of cognitive abilities during primate evolution. The hNP gene maps to chromosome 19q13, a region reportedly linked to schizophrenia and bipolar disorder. Therefore, hNP is a functional and positional candidate gene for association with schizophrenia, mood disorders, and cognitive ability. Polymorphism screening was performed for the entire hNP gene. The core promoter region was determined and whether or not transcriptional activity alters in an allele-dependent manner was examined by using the dual-luciferase system. Allelic and genotypic distributions of five single-nucleotide polymorphisms (SNPs) were compared between patients with schizophrenia (n=439), major depression (n=409), bipolar disorder (n=207), and controls (n=727). A possible association of the hNP genotype with memory index (assessed with Wechsler Memory Scale, revised, WMS-R) and intelligence quotient (IQ assessed with Wechsler Adult Intelligence Scale, revised; WAIS-R) was examined in healthy controls (n=166). A total of 28 SNPs, including nine novel SNPs, were identified. No significant effects on transcriptional activity were observed for SNPs in the promoter region. A significant allelic association was found between several SNPs and bipolar disorder (for SNP23 at the 3' regulatory region; odds ratio 1.48, 95% confidential interval 1.16-1.88, P=0.0015). However, such an association was not detected for schizophrenia or depression. Significant differences were observed between SNP23 and attention/concentration sub-scale score of WMS-R (P=0.016) and verbal IQ (P<0.001). Genetic variation of the hNP gene may contribute to molecular mechanisms of bipolar disorder and some aspects of memory and intelligence.
authors: Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors: Aiko
authors: A
authors: Izumi
authors: Yoshimi
authors: Y
authors: Iijima
authors: Hiroko
authors: H
authors: Noguchi
authors: Tadahiro
authors: T
authors: Numakawa
authors: Takeya
authors: T
authors: Okada
authors: Hiroaki
authors: H
authors: Hori
authors: Tadafumi
authors: T
authors: Kato
authors: Masahiko
authors: M
authors: Tatsumi
authors: Asako
authors: A
authors: Kosuga
authors: Kunitoshi
authors: K
authors: Kamijima
authors: Takashi
authors: T
authors: Asada
authors: Kunimasa
authors: K
authors: Arima
authors: Osamu
authors: O
authors: Saitoh
authors: Sadao
authors: S
authors: Shiosaka
authors: Hiroshi
authors: H
authors: Kunugi
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D001923:Brain Chemistry / Q000235:genetics*; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D003071:Cognition / Q000502:physiology*; D004252:DNA Mutational Analysis; D003866:Depressive Disorder / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D006801:Humans; D007360:Intelligence / Q000235:genetics; D007610:Kallikreins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics
chemical_list: C094799:KLK8 protein, human; D007610:Kallikreins