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

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.