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

BMC Psychiatry

Kazufumi Akiyama⁴  Kenichi Ohmori³  Harunobu Mori⁵  Toshihiko Inukai²  Kazutaka Shimoda¹  Kumiko Fujii¹  Takashi Watanabe¹  Yuji Ozeki¹  Atsushi Saito⁴  Go Kuratomi⁴ 

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

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

Others  :  1123918
DOI  :  10.1186/1471-244X-13-276

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

【 摘 要 】

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.

【 授权许可】

   
2013 Kuratomi et al.; licensee BioMed Central Ltd.

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