Liu Chao, Song Sijia, Zhang Junkai, Li Xiao, Gao Huijie
College of Pharmacy, Jining Medical University, Rizhao, Shandong, People's Republic of China.
Rizhao Mental Health Center, Rizhao, Shandong, People's Republic of China.
Neuropsychiatr Dis Treat. 2020 Jan 9;16:113-118. doi: 10.2147/NDT.S236298. eCollection 2020.
Several lines of evidence support the fact that the presence of oxidative stress plays an important role in the pathophysiological mechanisms of schizophrenia (SCZ). The glutathione peroxidases (GPXs) and glutathione S-transferases (GSTs) are the major antioxidant enzymes. Polymorphic variants of and can affect the antioxidant activities of their encoded enzymes. This study explored the possible associations of the and gene polymorphisms and schizophrenia in Chinese Han population.
DNA from 648 healthy controls and 617 schizophrenic patients was genotyped for single-nucleotide polymorphisms (SNPs) rs3957357 in and rs736775 in using a PCR-LDR genotyping assay. The χ test compared differences in genetic distributions between the two groups in a case-control study. The generalized multifactor dimensionality reduction (GMDR) was used to explore the interaction between the GSTA1 gene and the GPX3 gene on the risk of SCZ.
Significant differences in allelic and genotypic frequencies of rs3957357 were present between SCZ and control groups ( rs3957357 χ=6.172, =0.046 by genotype, χ=5.847, =0.016, odds ratio=1.329, 95% confidence interval=1.055-1.674 by allele). No significant differences in allelic or genotypic frequencies of rs736775 were detected between cases and controls ( rs736775: χ=2.058, =0.357 by genotype, χ=1.853, =0.173, odds ratio=1.131, 95% confidence interval=0.953-1.342 by allele). Moreover, the GMDR model showed that the interaction between rs3957357 and rs736775 was associated significantly with SCZ risk, =0.0107.
Our results suggest that rs3957357 SNP has an effect on the risk of SCZ and the interaction between rs3957357and rs736775 may affect the development of SCZ in Chinese Han population. However, these results should be validated by replication in different populations with large sample sizes.
多项证据支持氧化应激的存在在精神分裂症(SCZ)的病理生理机制中起重要作用这一事实。谷胱甘肽过氧化物酶(GPXs)和谷胱甘肽S-转移酶(GSTs)是主要的抗氧化酶。GSTA1和GPX3的多态性变体可影响其编码酶的抗氧化活性。本研究探讨了中国汉族人群中GSTA1和GPX3基因多态性与精神分裂症之间可能的关联。
采用PCR-LDR基因分型检测法,对648名健康对照者和617名精神分裂症患者的DNA进行GSTA1基因rs3957357和GPX3基因rs736775单核苷酸多态性(SNP)基因分型。在病例对照研究中,采用χ²检验比较两组间基因分布的差异。采用广义多因素降维法(GMDR)探讨GSTA1基因与GPX3基因相互作用对SCZ风险的影响。
SCZ组与对照组之间GSTA1基因rs3957357的等位基因频率和基因型频率存在显著差异(GSTA1基因rs3957357:基因型χ²=6.172,P=0.046;等位基因χ²=5.847,P=0.016,优势比=1.329,95%置信区间=1.055-1.674)。病例组与对照组之间未检测到GPX基因rs736775的等位基因频率或基因型频率有显著差异(GPX3基因rs736775:基因型χ²=2.058,P=0.357;等位基因χ²=1.853,P=0.173,优势比=1.131,95%置信区间=0.953-1.342)。此外,GMDR模型显示GSTA1基因rs3957357与GPX3基因rs736775之间的相互作用与SCZ风险显著相关,P=0.0107。
我们的研究结果表明,GSTA1基因rs3957357 SNP对SCZ风险有影响,且GSTA1基因rs3957357与GPX3基因rs736775之间的相互作用可能影响中国汉族人群SCZ的发生发展。然而,这些结果应在不同人群中进行大样本重复验证。