title: Genetic variant in NDUFS1 gene is associated with schizophrenia and negative symptoms in Han Chinese.
abstract: Abnormalities in mitochondrial complex I, which is responsible for controlling mitochondrial function, have been implicated in a variety of diseases associated with mitochondrial dysfunction, potentially including schizophrenia. The NADH dehydrogenase Fe-S protein 1 (NDUFS1) is the largest subunit of complex I. To explore whether the encoding NDUFS1 gene confers susceptibility to schizophrenia or is associated with the severity of typical symptoms of schizophrenia, we recruited 519 stable schizophrenia patients receiving clozapine treatment and 594 healthy controls for genotyping to investigate the association of four selected tagging single-nucleotide polymorphisms (SNPs) of NDUFS1 and both schizophrenia risk and symptom severity. The severity of psychotic symptoms was evaluated using the Positive and Negative Syndrome Scale and then tested for association with the four SNPs. The SNP rs1044120 showed significant association with schizophrenia (adjusted P=0.032). The frequency of the G allele of rs1044120 was significantly higher in patients than among the healthy controls (adjusted P=0.008). Stratification by sex revealed a significant association between the rs1044120 polymorphism and schizophrenia among males (adjusted P=0.036 and 0.008 in genotypic and allelic comparisons, respectively). We also observed a significant difference in the negative symptom scores among the three genotypes among these males (adjusted P=0.036). Post hoc comparisons showed that rs1044120 G/G carriers had higher negative symptom scores than those with G/T and T/T carriers (raw P=0.035 and 0.005, respectively). Our findings suggest that NDUFS1 may confer susceptibility to schizophrenia in male subjects, acting as a causative factor for the severity of negative symptoms in schizophrenia.
authors.affiliation: Department of Psychiatry, The Third Hospital of Quzhou, Zhejiang, China.
authors.forename: Yunlong
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Psychiatry, The Third Hospital of Quzhou, Zhejiang, China.
authors.forename: Zhongliang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Psychiatry, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, China.
authors.forename: Jianliang
authors.initials: J
authors.lastname: Ni
authors.affiliation: Schizophrenia Program, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Schizophrenia Program, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Meijuan
authors.initials: M
authors.lastname: Chen
authors.affiliation: Schizophrenia Program, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Cai
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Li
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Schizophrenia Program, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Zhang
mesh_terms: D044466:Asian People / Q000235:genetics; D003024:Clozapine / Q000627:therapeutic use; D005260:Female; D056726:Genetic Association Studies; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D009245:NADH Dehydrogenase / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D020033:Protein Isoforms / Q000235:genetics; D012559:Schizophrenia / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D012702:Serotonin Antagonists / Q000627:therapeutic use; D012737:Sex Factors
chemical_list: C487793:NDUFS1 protein, human; D020033:Protein Isoforms; D012702:Serotonin Antagonists; D009245:NADH Dehydrogenase; D003024:Clozapine