Progress in Neuro-Psychopharmacology and Biological Psychiatry
No association found between the promoter variations of QKI and schizophrenia in the Chinese population
Introduction
Schizophrenia is a common, chronic and complex mental disorder characterized by disturbances of perception, emotion, social functioning, and cognition, caused by genetic and environmental factors (Gottesman and Shields, 1967, McGuffin et al., 1995). Twin and adoption studies have demonstrated a substantial genetic element in schizophrenia with a heritability factor of ~ 80% (Cannon et al., 1998, McGuffin et al., 1995). The specific genes involved in the development of schizophrenia have proved difficult to identify suggesting that many different genes underlie the genetic component of this disorder. Evidence from linkage studies have implicated several susceptibility loci , including 1q, 2p, 6p, 8p, 13q, 22q chromosome regions and other locations in the genome (Badner and Gershon, 2002, Harrison and Weinberger, 2005, Lewis et al., 2003, Shirts and Nimgaonkar, 2004). A series of studies have also reported association between chromosome 6q13–6q26 and schizophrenia (Cao et al., 1997, Duan et al., 2004, Edgar et al., 2000, Kaufmann et al., 1998, Lerer et al., 2003, Levinson et al., 2000, Lindholm et al., 2001, Martinez et al., 1999). The quaking homolog, KH domain RNA binding (QKI) located in this area is a new gene which has been reported to be associated with schizophrenia (Aberg et al., 2006a, Aberg et al., 2006b, McCullumsmith et al., 2007). QKI is a member of the signal transduction and activation of RNA (STAR) protein family (Lin et al., 1997). This gene is highly conserved over different species and is important for normal development in both vertebrates and invertebrates (Chen and Richard, 1998, Vernet and Artzt, 1997). It contains an RNA-binding domain which can bind directly to several different sequence motifs of cellular RNA (Chen et al., 1997, Galarneau and Richard, 2005, Larocque et al., 2005, Larocque et al., 2002, Wu et al., 2002). The QKI is mostly expressed in the oligodendrocytes (Hardy et al., 1996, Li et al., 2002, Wu et al., 1999). The different isoforms of QKI regulate RNA metabolism of several myelin structure genes as well as differentiation of progenitor cells into oligodendrocytes (Larocque et al., 2005, Larocque et al., 2002, Wu et al., 1999). The expression of QKI has been reported to be correlated with MAG, CNP, PLP1 and TF in the human brain (Aberg et al., 2006a, McCullumsmith et al., 2007). The role it plays in both oligodendrocyte genesis and myelination suggests that abnormalities of QKI expression may result in the abnormal oligodendrocyte- and myelin-related gene expressions which have been observed in schizophrenias (Haroutunian et al., 2006).
Recently, several studies have reported that the mRNA expression of QKI in the human brain is different in individuals diagnosed with schizophrenia compared with healthy subjects (Aberg et al., 2006a, Haroutunian et al., 2006). The functional study of QKI suggests that the dysfunction of QKI may cause some phenotypes as observed in schizophrenia (Sidman et al., 1964, Ebersole et al., 1996). In this study we examined whether the genetic variants around the promoter region of QKI are associated with schizophrenia, and carried out a case-control study in the Han Chinese population (Fig. 1).
Section snippets
Subject
We studied 288 unrelated individuals diagnosed with schizophrenia (163 Males and 125 females with a mean age of 25.87years, SD = 7.58), and 288 control subjects (159 Males and 129 females with a mean age of 35.02years, SD = 8.16) for rs4263561, rs3904720, rs387504, rs3763197, rs7772756, rs7758706 and rs4709716. The average onset age of disease was 25.87, SD = 7.58 (Supplement 1, 2). The minimum age of our controls is 21. All patients were recruited from the Shanghai Mental Health Center. All
Results
A total of 288 cases and 288 controls were studied in our experiment. The power of rs4263561, rs3904720, rs3857504, rs3763197, rs7772756, rs7758706 and rs4709716 were of 0.865, 0.750, 0.805, 0.862, 0.851, 0.857 and 0.867 respectively, with an odds ratio (OR) of 1.5 (95% confidence interval [CI]). The observed genotype frequencies of all SNPs were within the distribution expected according to HWE (Supplement 3).
No significant difference was observed in individual SNP marker alleles or genotype
Discussion
Although several other lines of evidences support the hypothesis that there is an association between QKI and schizophrenia (Aberg et al., 2006a, Haroutunian et al., 2006), no significant difference of allele and genotype frequencies was observed in our Chinese population. The statistical power of our study was also enough to detect an association between the variants and schizophrenia. The seven polymorphisms we selected in our study were in Hardy–Weinberg equilibrium. In the haplotypic
Acknowledgments
We would sincerely thank all the subjects for their participation in this study and all the medical staff involved in sample collecting. This work was supported by grants from the Knowledge Innovation Program of the Chinese Academy of Sciences, Grant No. KSCX2-YW-R-01, the national 863 programs (NO.2006AA02A407) of China, the Shanghai Municipal Commission for Science and Technology and Shanghai Leading Academic Discipline Project (B205).
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2017, Brain ResearchCitation Excerpt :We have previously demonstrated that QKI, KH domain containing, RNA Binding (QKI), which is exclusively expressed by glial cells, is a candidate gene for SCZ (Aberg et al., 2006b). This finding has been replicated by Haroutunian et al. (2006) and McCullumsmith et al. (2007), although was not found by (Huang et al., 2009). The QKI locus generates five alternative mRNA isoforms (QKI5, QKI6, QKI6B, QKI7, and QKI7B), of which all but QKI6B have previously been examined in SCZ brains.
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These authors contributed equally to this work.