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. 2020 Feb;17(2):140-146.
doi: 10.30773/pi.2019.0175. Epub 2020 Feb 13.

Association of the Promoter Haplotype of IFN-γ-Inducible Protein 16 Gene with Schizophrenia in a Korean Population

Won Sub Kang  1 , Su Kang Kim  2 , Hae Jeong Park  3
Affiliations

Association of the Promoter Haplotype of IFN-γ-Inducible Protein 16 Gene with Schizophrenia in a Korean Population

Won Sub Kang et al. Psychiatry Investig. 2020 Feb.

Abstract

Objective: Viral infections play an important role in the development of schizophrenia, inducing the faulty immunological responses and aberrant inflammation. IFN-γ-inducible protein 16 (IFI16) is an immunological DNA sensor against viral infections, triggering the inflammatory responses. In this study, we investigated an association between putative promoter single nucleotide polymorphisms (SNPs) and haplotypes of IFI16 and schizophrenia.

Methods: A total of 280 schizophrenia patients and 427 control subjects were recruited in this study. We genotyped three promoter SNPs (rs1465175, rs3754464, rs1417806) using direct sequencing. Associations of SNPs and haplotypes of IFI16 with schizophrenia were analyzed. The promoter activities on the haplotypes of IFI16 were measured.

Results: The T allele of rs1465175 and the C allele of rs1417806 were protectively associated with schizophrenia (p=0.021 on rs1465175; p=0.016 on rs1417806), whereas the G allele of rs3754464 was associated with an increased risk of schizophrenia (p=0.019). In haplotype analysis, a significant association between the GGA haplotype and schizophrenia was shown (p=0.013). Moreover, we found that the GGA haplotype elevated the promoter activity compared to the GAA haplotype, whereas the TAC haplotype reduced that.

Conclusion: The promoter SNPs and haplotypes of IFI16 may contribute to the susceptibility of schizophrenia, affecting the promoter activity of IFI16.

Keywords: IFN-γ-inducible protein 16; Promoter activity; Schizophrenia; Single nucleotide polymorphisms.

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Conflict of interest statement

The authors have no potential conflicts of interest to disclose.

Figures

Figure 1.
Figure 1.
Effect of the haplotypes of IFI16 on the promoter activity. Luciferase activities of the haplotypes of IFI16 are presented relative to those of reference haplotype, the GAA haplotype. Data represent the mean of three individual experiments performed in triplicate (N=9 for each haplotype). *p<0.01 compare with relative luciferase activity of the GAA haplotype. IFI16: IFN-γ-inducible protein 16.
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