Kang Won Sub, Kim Su Kang, Park Hae Jeong
Department of Neuropsychiatry, School of Medicine, Kyung Hee University, Seoul, Republic of Korea.
Department of Biomedical Laboratory Science, Catholic Kwandong University, Gangneung, Republic of Korea.
Psychiatry Investig. 2020 Feb;17(2):140-146. doi: 10.30773/pi.2019.0175. Epub 2020 Feb 13.
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.
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.
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.
The promoter SNPs and haplotypes of IFI16 may contribute to the susceptibility of schizophrenia, affecting the promoter activity of IFI16.
病毒感染在精神分裂症的发病过程中起重要作用,可诱发免疫反应异常和炎症反应异常。γ干扰素诱导蛋白16(IFI16)是一种针对病毒感染的免疫DNA传感器,可触发炎症反应。在本研究中,我们调查了IFI16假定启动子单核苷酸多态性(SNP)和单倍型与精神分裂症之间的关联。
本研究共招募了280例精神分裂症患者和427名对照受试者。我们采用直接测序法对三个启动子SNP(rs1465175、rs3754464、rs1417806)进行基因分型。分析IFI16的SNP和单倍型与精神分裂症的关联。检测IFI16单倍型的启动子活性。
rs1465175的T等位基因和rs1417806的C等位基因与精神分裂症呈保护性关联(rs1465175,p = 0.021;rs1417806,p = 0.016),而rs3754464的G等位基因与精神分裂症风险增加相关(p = 0.019)。单倍型分析显示,GGA单倍型与精神分裂症之间存在显著关联(p = 0.013)。此外,我们发现GGA单倍型相比GAA单倍型提高了启动子活性,而TAC单倍型则降低了启动子活性。
IFI16启动子SNP和单倍型可能与精神分裂症易感性有关,影响IFI16的启动子活性。