title: Association of the Hermansky-Pudlak syndrome type 4 (HPS4) gene variants with cognitive function in patients with schizophrenia and healthy subjects.
abstract: BACKGROUND
  The Hermansky-Pudlak Syndrome Type 4 (HPS4) gene, which encodes a subunit protein of the biogenesis of lysosome-related organelles complex (BLOC)-3, which is involved in late endosomal trafficking, is associated with schizophrenia; however, its clinical relevance in schizophrenia remains unknown. The purpose of the present study was to investigate whether HPS4 is associated with cognitive functions in patients with schizophrenia and healthy controls and with the clinical profiles of patients with schizophrenia.
  
  
  METHODS
  We investigated the association of variants of HPS4 with clinical symptoms and cognitive function in Japanese patients with schizophrenia (n = 240) and age-matched healthy control subjects (n = 240) with single nucleotide polymorphisms (SNP)- or haplotype-based linear regression. We analyzed five tagging SNPs (rs4822724, rs61276843, rs9608491, rs713998, and rs2014410) of HPS4 and 2-5 locus haplotypes of these five SNPs. The cognitive functions of patients and healthy subjects were evaluated with the Brief Assessment of Cognition in Schizophrenia, Japanese-language version, and the patients were assessed for their symptomatology with the Positive and Negative Symptom Scale (PANSS).
  
  
  RESULTS
  In patients with schizophrenia, rs713998 was significantly associated with executive function under the dominant genetic model (P = 0.0073). In healthy subjects, there was a significant association between working memory and two individual SNPs under the recessive model (rs9608491: P = 0.001; rs713998: P = 0.0065) and two haplotypes (rs9608491-713998: P = 0.0025; rs61276843-9608491-713998: P = 0.0064). No significant association was found between HPS4 SNPs and PANSS scores or premorbid IQ, as measured by the Japanese version of the National Adult Reading Test.
  
  
  CONCLUSIONS
  These findings suggested the involvement of HPS4 in the working memory of healthy subjects and in the executive function deficits in schizophrenia.
authors.forename: Go
authors.initials: G
authors.lastname: Kuratomi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Saito
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ozeki
authors.forename: Takashi
authors.initials: T
authors.lastname: Watanabe
authors.forename: Kumiko
authors.initials: K
authors.lastname: Fujii
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Shimoda
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Inukai
authors.forename: Harunobu
authors.initials: H
authors.lastname: Mori
authors.forename: Kenichi
authors.initials: K
authors.lastname: Ohmori
authors.affiliation: Department of Biological Psychiatry and Neuroscience, Dokkyo Medical University School of Medicine, 880 Kitakobayashi, Mibu, Tochigi 3210293, Japan. kazufuak@dokkyomed.ac.jp.
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Akiyama
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D003071:Cognition / Q000502:physiology*; D003072:Cognition Disorders / Q000150:complications / Q000235:genetics* / Q000523:psychology; D056344:Executive Function / Q000502:physiology; D005260:Female; D020662:Guanine Nucleotide Exchange Factors; D006239:Haplotypes; D006801:Humans; D008247:Lysosomes; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology; D008875:Middle Aged; D009483:Neuropsychological Tests; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D012559:Schizophrenia / Q000150:complications / Q000235:genetics*; D012565:Schizophrenic Psychology; D055815:Young Adult
chemical_list: D020662:Guanine Nucleotide Exchange Factors; C451752:HPS4 protein, human; D011506:Proteins