Abstract:

Semaphorins are ligands of plexins, and the plexin-semaphorin signaling system is widely involved in many neuronal events including axon guidance, cell migration, axon pruning, and synaptic plasticity. The plexin A2 gene (PLXNA2) has been reported to be associated with schizophrenia. This finding prompted us to examine the possible association between the semaphorin 3D gene (SEMA3D) and schizophrenia in a Japanese population. We genotyped 9 tagging single nucleotide polymorphisms (SNPs) of SEMA3D including a non-synonymous variation, Lys701Gln (rs7800072), in a sample of 506 patients with schizophrenia and 941 healthy control subjects. The Gln701 allele showed a significant protective effect against the development of schizophrenia (p = 0.0069, odds ratio = 0.76, 95% confidence interval 0.63 to 0.93). Furthermore, the haplotype-based analyses revealed a significant association. The four-marker analysis (rs2190208-rs1029564-rs17159614-rs12176601), in particular, not including the Lys701Gln, revealed a highly significant association (p = 0.00001, global permutation), suggesting that there may be other functional polymorphisms within SEMA3D. Our findings provide strong evidence that SEMA3D confers susceptibility to schizophrenia, which could contribute to the neurodevelopmental impairments in the disorder.

日本語要旨:

プレキシン-セマフォリンのシグナル伝達は神経機能に広く係わっていることが知られている。プレキシンA2遺伝子と統合失調症との遺伝学的相関が見いだされたので、セマフォリン３D遺伝子(SEMA3D)との相関を検討した。その結果、4個のマーカーが強い相関(p=0,00001)を示し、統合失調症の罹患性に関わる事が明らかになった。