Journal of Shanghai Jiao Tong University (Medical Science) >

2021 , Vol. 41 >Issue 12: 1613 - 1617

DOI: https://doi.org/10.3969/j.issn.1674-8115.2021.12.010

Basic research

Association study of HRAS proto-oncogene single nucleotide polymorphism with schizophrenia and therapeutic response to atypical antipsychotics

  • Rui LI ,
  • Duan ZENG ,
  • Shen HE ,
  • Yi-feng SHEN ,
  • Hua-fang LI
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  • 1.Department of Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
    2.Shanghai Clinical Research Center for Mental Health, Shanghai 200030, China
    3.Shanghai Key Laboratory of Psychotic Disorders, Shanghai 200030, China
LI Hua-fang, E-mail: lhlh-5@163.com.

Received date: 2021-05-13

  Online published: 2021-01-28

Supported by

Project of Shanghai Clinical Research Center for Mental Health(19MC1911100);Shanghai Jiao Tong University Interdisciplinary Research Grant(YG2017MS42);Shanghai Collaborative Innovation Center for Translational Medicine(TM201727);Innovation Program for Ph.D. Students in Shanghai Jiao Tong University School of Medicine(BXJ201955);Shanghai Outstanding Youth Training Program in Public Health(GWV-10.2-YQ45)

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Abstract

Objective

·To investigate the relation of HRAS proto-oncogene (HRAS) polymorphism in rs11246176 with schizophrenia and therapeutic response to atypical antipsychotics in the Chinese Han population.

Methods

·A total of 460 schizophrenia patients with acute attack (case group) and 386 healthy controls (control group) were recruited. The patients were treated with atypical antipsychotics and followed up for 26 weeks. Positive and Negative Syndrome Scale (PANSS) were used to evaluate the patients' conditions at the time of enrollment, and 13 weeks and 26 weeks after enrollment respectively. The reduction rates at 26th week were calculated as the standard for drug efficacy (the reduction rate ≥50% was considered effective, and <50% was considered ineffective), and then the patients were divided into the responder group and the non-responder group. The peripheral blood samples were collected to extract DNA. Rs11246176 was genotyped by using TaqMan assays. SHEsis software and SNPstats software were used to compare the frequency distributions of alleles, genotypes, and genotypes under different genetic models between the case group and the control group as well as between the responder group and the non-responder group. In addition, expression quantitative trait loci (eQTL) analysis was used to explore the difference in HRAS expression in the brain among different rs11246176 genotypes.

Results

·There were no significant differences in the distribution of allelic and genotypic frequencies between the case group and the control group (P>0.05). The frequency of A allele in the responder group was higher than that in the non-responder group (P=0.010). The frequency of AA and AG genotypes in the responder group was higher than that in the non-responder group (P=0.040). The reduction rate of PANSS of the patients with AA or AG genotype 26th week was significantly higher than that of the patients with GG genotype (P=0.010). Furthermore, the brain eQTL analysis revealed that in the dorsolateral prefrontal cortex of normal Caucasians and African Americans, the HRAS mRNA expression level of the AA genotype was the highest, followed by the AG genotype and the GG genotype in the order (P=0.000).

Conclusion

·Rs11246176 polymorphism in HRAS gene is not associated with the occurrence of schizophrenia in the Chinese Han population, but may be related to therapeutic response to atypical antipsychotics. A allele carriers may have better response to atypical antipsychotics.

Key words： schizophrenia; HRAS proto-oncogene; single nucleotide polymorphism (SNP); rs11246176; atypical antipsychotics

Cite this article

Rui LI , Duan ZENG , Shen HE , Yi-feng SHEN , Hua-fang LI . Association study of HRAS proto-oncogene single nucleotide polymorphism with schizophrenia and therapeutic response to atypical antipsychotics[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2021 , 41(12) : 1613 -1617 . DOI: 10.3969/j.issn.1674-8115.2021.12.010

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