The International Journal of Neuropsychopharmacology

Research Article

Evidence for association between the 5' flank of the NOS1 gene and schizophrenia in the Chinese population

Wei Tanga1a2a3, Ke Huanga1a2a3, Ruqi Tanga1a2, Guoquan Zhoua3, Chao Fanga1, Jing Zhanga1a2, Lingzhen Dua4, Guoying Fenga5, Lin Hea2 and Yongyong Shia1a2a4 c1

a1 Bio-X Center, Shanghai Jiao Tong University, Shanghai, P.R. China

a2 Institute for Nutritional Sciences, Shanghai Institute of Biological Sciences, Chinese Academy of Sciences, Shanghai, P.R. China

a3 Changning Institute of Mental Health, the Bio-X Center Hospital, Shanghai, China

a4 Luwan Branch of Ruijin Hospital, Shanghai, China

a5 Shanghai Institute of Mental Health, Shanghai, P.R. China


Nitric oxide (NO) plays an important role in the dopaminergic and serotonergic system as the second messenger of the NMDA receptor and has possible roles in neurotransmission, neurosecretion, synaptic plasticity, and tissue injury in many neurological disorders, including schizophrenia. There is also genetic evidence to support the human NOS1 (neuronal nitric oxide synthase 1) gene as a promising candidate gene associated with schizophrenia. In this paper we conducted a case-control association study involving 1705 Chinese subjects and 12 genetic markers [11 single nucleotide polymorphisms (SNPs) and 1 microsatellite] mainly in the 5' flank region of the gene by direct sequencing and capillary electrophoresis. We identified SNP rs3782206 and several haplotypes derived from it as being significantly associated with schizophrenia and, specifically, in a paranoid subgroup. Our results strongly support a previous hypothesis that NOS1 contributes to the genetic risk of schizophrenia and suggest that further research on more NOS1 variants and its regular elements are warranted.

(Received December 28 2007)

(Reviewed February 03 2008)

(Revised April 14 2008)

(Accepted April 15 2008)

(Online publication June 11 2008)


c1 Address for correspondence: Yongyong Shi, Ph.D., Bio-X Center, Shanghai Jiao Tong University, PO Box 501, Haoran Building, 1954 Huashan Road, Shanghai 200030, P.R. China. Tel.: +86 21 62822491 Fax: +86 21 62822491. E-mail:


† These authors contributed equally to this work.