Common variants in QPCT gene confer risk of schizophrenia in the Han Chinese population

Abstract

Schizophrenia (SCZ) is a common and severe mental disorder, its etiology has not been elucidated completely. In one previous genome-wide association study (GWAS) of SCZ in the Caucasian population, the QPCT has been reported as susceptible gene for SCZ. The QPCT gene encodes Glutaminyl cyclase (QC), an enzyme which is involved in the post translational modification by converting N-terminal glutamate of protein to pyroglutamate, which is resistant to protease degradation, more hydrophobic, and prone to aggregation and neurotoxic. To further investigate the role of this gene in the pathogenesis of schizophrenia in the Han Chinese population, we conducted this study in 1,248 (Mean age ± S.D, 36.44 years ± 9.0) SCZ cases, 1,248 (Mean age ± S.D, 30.62 years ± 11.35) healthy control samples for a case control study. We genotyped six SNPs in this study, including one positive SNP of the previous study, using the Sequenom MassARRAY platform. We found that rs2373000 was significantly associated with SCZ before correction [rs2373000: P allele = 0.016, χ(2) = 5.784, OR [95%CI] = 0.861 [0.762-0.972], P genotype = 0.018, χ(2) = 0.069]. After permutation correction for multiple testing, rs2373000 [rs2373000: P Allele corrected = 0.063, P genotype corrected = 0.069] showed marginal association with SCZ. Additionally, one pathogenic haplotype (TGT) containing rs2373000 was also significantly associated with SCZ. Our results are consistent with the findings of previous study and the genetic risk of QPCT gene for SCZ also exists in the Han Chinese population.

CalPen (Calculator of Penetrance), a web-based tool to estimate penetrance in complex genetic disorders

“…15q11.2 deletions, which also represent variants of uncertain significance, have the lowest average penetrance (~1.4%). We also estimated the penetrance values of 128 SNPs using a large set of data reported by the psychiatric Genetics Consortium [29] and other reports that identified 17 SNPs among schizophrenia patients [15][16][17][18][19][20][21][22][23][24][25][26][27][28]; (Table 3). In contrast to CNVs, the odds ratios of the SNPs are always lower, rarely approach a ratio of 1.5 [32] and therefore are likely to have lesser penetrance than CNVs.…”

“…We then performed a thorough literature search and extracted the frequencies of these 15 CNVs from different case-control studies [8][9][10][11][12][13][14]. In addition, we also obtained frequencies from a different set of case-control studies that identified 145 SNPs associated with schizophrenia [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29]; (Table 3). Of these, 128 were identified by the Psychiatric Genetics Consortium [29].…”

Identification of Potential Core Genes and Promising Compounds in STEMI Using Bioinformatics Analysis

“…As the development of atherosclerosis and ischemia progresses, in ammation plays a critical role [43]. Glutaminyl-peptide cyclotransferase (QPCT) gene encodes glutaminyl cyclase (QC) [44].…”

Epigenetic Alterations in Renal Cell Cancer With TKIs Resistance: From Mechanisms to Clinical Applications

“…The methylation of glutaminyl peptide cyclotransferase (QPCT) gene had been reported to associate with sunitinib resistance through Ras/Raf/ERK signaling pathway (Zhao et al, 2019). The QPCT gene encodes glutaminyl cyclase (QC), an enzyme that is involved in the posttranslational modification by converting the N-terminal glutaminyl and glutamyl into pyroglutamate through cyclization, making the protein more resistant to protease degradation, more hydrophobic, and more prone to aggregation and neurotoxicity (Khan et al, 2016;Vijayan and Zhang, 2019). Hypomethylated QPCT gene increased the expression of QC, the process promoted by the NF-κB signaling (p65; Kehlen et al, 2013), leading to upregulation of HRAS and activation of the Ras/Raf/ERK signaling pathway (Herrero et al, 2016;Michael et al, 2016;Zhao et al, 2019).…”