No association found between the promoter variations of QKI and schizophrenia in the Chinese population

Abstract

Background

Schizophrenia is a chronic psychiatric disorder with a strong genetic component. Several recent published studies have reported that the mRNA expression level of quaking homolog, KH domain RNA binding (QKI) is down regulated in individuals diagnosed with schizophrenia.

Methods

We were interested in the genetic variants around the promoter region of QKI and selected seven variants in this region, namely rs4263561, rs3904720, rs387504, rs3763197, rs7772756, rs7758706 and rs4709716. For the study we recruited 288 individuals diagnosed with schizophrenia and 288 control subjects. All the recruits were from Shanghai and were Han Chinese in origin.

Results

No individual SNP nor any haplotype was found to be associated with schizophrenia.

Conclusions

These results suggest that the variants within the promoter region of QKI gene are unlikely to play a major role in susceptibility to 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).