Abstract
BackgroundRecent research has implicated that mutations in the neurexin-1 (NRXN1) gene on chromosome 2p16.3 might play a role in schizophrenia, autism, and nicotine dependence. In order to explore the association of NRXN1 polymorphisms with schizophrenia, we made a case-control association study in Chinese Han population.MethodsWe examined six tag single nucleotide polymorphisms (SNPs) spanning 116.7 kb of NRXN1 in 768 schizophrenic patients and 738 healthy control subjects. The association of NRXN1 polymorphisms with schizophrenia and the age-at-onset of this disease were explored.ResultsOur results showed that four SNPs of NRXN1 gene were significantly associated with schizophrenia (rs10490168: G > A, p = 0.017; rs2024513: A > G, p = 0.006; rs13382584: T > C, p = 0.009; and rs1558852: G > A, p = 0.031). Furthermore, the association of SNP rs2024513 with schizophrenia remained significance after the Bonferroni correction. Haplotypes consisting of above six SNPs also showed significantly associated with schizophrenia (global chi-square = 14.725, p = 0.022). A protective haplotype AGTGCA remained associated with schizophrenia, even after 10,000 permutation tests (empirical p-value = 0.043). However, we did not find any association with age-at-onset of schizophrenia with NRXN1 polymorphisms.ConclusionsOur findings suggest that NRXN1 might represent a major susceptibility gene for schizophrenia in Chinese Han population.
Highlights
Recent research has implicated that mutations in the neurexin-1 (NRXN1) gene on chromosome 2p16.3 might play a role in schizophrenia, autism, and nicotine dependence
Six single nucleotide polymorphisms (SNPs) in the neurexin 1 (NRXN1) gene were genotyped in 768 schizophrenia patients and 738 healthy control subjects of Chinese Han population
We investigated the association of NRXN1 polymorphisms and schizophrenia in 768 cases and 738 healthy control subjects of Chinese Han population
Summary
Recent research has implicated that mutations in the neurexin-1 (NRXN1) gene on chromosome 2p16.3 might play a role in schizophrenia, autism, and nicotine dependence. Schizophrenia is a common psychiatric disorder characterized by profound disturbances of thinking, emotion, and social functioning. It affects approximately 1% of the worldwide population and accounts for about 2.5% of healthcare costs [1]. Kirov et al have found a deletion disrupting the NRXN1 gene at 2p16.3 in a mother and Neurexins, including NRXN1, NRXN2, NRXN3, are cell-surface receptors that bind neuroligins (NLGNs) and form a Ca2+-dependent neurexin/neuroligin complex at synapses in the central nervous system [12,13]. There is prevailing evidence implicating both neurexins and neuroligins as primary factors in neuropsychiatric disorders [3,4,5,6,7,8,9,10,11]
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