JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE) ›› 2021, Vol. 41 ›› Issue (1): 29-34.doi: 10.3969/j.issn.1674-8115.2021.01.005

• Basic research • Previous Articles     Next Articles

Association study of non-coding variant of NOS1AP gene with schizophrenia

Guo-qin HU1(), Qin-yu LÜ2, Jing ZHAO2, Ming-huan ZHU3, Shun-ying YU2, Zheng-hui YI2(), Jian CHEN1()   

  1. 1.Psychiatry Department, Shanghai Mental Health Center of Huangpu District, Shanghai 200011, China
    2.Psychiatry Department, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
    3.Psychiatry Department, Shanghai Pudong New Area Mental Health Center, Shanghai 200122, China
  • Online:2021-01-28 Published:2021-02-22
  • Contact: Zheng-hui YI,Jian CHEN E-mail:huguoqin1990@126.com;yizhenghui1971@163.com;chenjian20001967@163.com
  • Supported by:
    Funding Information] Scientific Research Project of Shanghai Huangpu District Science and Technology Commission(HKQ201813);Shanghai Huangpu District Health and Family Planning Professional Talent Echelon Training Plan(2019GG11);Scientific Research Project of Shanghai Municipal Health Committee(20194Y0406)

Abstract: Objective

·To clarify the correlation between nitric oxide synthase 1 adaptor protein (NOS1AP)gene and Han Chinese schizophrenia patients, and predict the changes in the secondary structure of RNA and protein caused by variation of NOS1AP gene positive polymorphism.

Methods

·From October 2012 to December 2015, 333 patients with early onset schizophrenia (EOS) and 491 patients with non-early onset schizophrenia (non-EOS) were included from Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, and 901 healthy controls (HC) were selected from the staff of Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine and the people receiving physical examination in the Physical Examination Center of Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University through recruitment. The rs12742393, rs4145621 and rs1415263 polymorphisms of NOS1AP gene were detected by TaqMan probe. The Hardy-Weinberg (H-W) equilibrium of the three polymorphism loci and the allele and genotype frequencies were analyzed by the SHEsis online software. The optimal genetic model analysis was carried out by the SNPstats online website. RNAfold and DNAstar softwares were used to predict the secondary structures of RNA and protein encoded by the significantly different polymorphism locus.

Results

·The distribution of genotypes fit H-W equilibrium(P>0.05). There were significant difference in allele and genotype frequencies between EOS patients and HC subjects for rs12742393 after Bonferroni correction (P=0.012, P=0.039). Genetic model analysis found that the distribution of genotypes best fit the dominant genetic pattern (P=0.004). After the mutation of the A allele into the C allele for rs12742393, the secondary structures of RNA and protein encoded by the NOS1AP gene underwent important changes, resulting in the decrease in spatial stability.

Conclusion

·The NOS1AP rs12742393 polymorphism has a major influence on susceptibility to EOS.

Key words: schizophrenia, nitric oxide synthase 1 adaptor protein(NOS1AP) gene, polymorphism, secondary structure, bioinformatics

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