Association of the Hermansky–Pudlak syndrome type 4 (HPS4) gene variants with cognitive function in patients with schizophrenia and healthy subjects

BMC Psychiatry

Research Article

Kazufumi Akiyama¹  Go Kuratomi¹  Atsushi Saito¹  Toshihiko Inukai²  Kazutaka Shimoda³  Takashi Watanabe³  Yuji Ozeki³  Kumiko Fujii³  Harunobu Mori⁴  Kenichi Ohmori⁵ 

[1] Department of Biological Psychiatry and Neuroscience, Dokkyo Medical University School of Medicine, 880 Kitakobayashi, 3210293, Mibu, Tochigi, Japan;Department of Internal Medicine (Endocrinology, Metabolism, and Hematology), Dokkyo Medical University Koshigaya Hospital, 2-1-50 Minamikoshigaya, 3438555, Koshigaya, Saitama, Japan;Department of Psychiatry, Dokkyo Medical University School of Medicine, 880 Kitakobayashi, 3210293, Mibu, Tochigi, Japan;Mori Hospital, 419 Iidamachi, 3210347, Utsunomiya, Tochigi, Japan;Takizawa Hospital, 2-29 Hanabusahoncho Utsunomiya, 3200828, Tochigi, Japan;

关键词: HPS4;    Cognition;    Working memory;    Executive function;    BACS;    rs9608491;    rs713998;   

DOI  :  10.1186/1471-244X-13-276

 received in 2013-08-27, accepted in 2013-10-25,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundThe 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.MethodsWe 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).ResultsIn 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.ConclusionsThese findings suggested the involvement of HPS4 in the working memory of healthy subjects and in the executive function deficits in schizophrenia.

【 授权许可】

Unknown   
© Kuratomi et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.