A new single-nucleotide mutation (rs362719) of the reelin (RELN) gene associated with schizophrenia in female Chinese Han

Abstract

ABSTRACT.Reelin is an extracellular signaling protein that plays an important role in the development of the central nervous system. Postmortem studies have shown lower reelin protein levels in the brains of patients with schizophrenia and bipolar disorder compared with controls. Genetic studies have also shown that mutations in the reelin gene (RELN) increase the risk for schizophrenia and bipolar disorder. We evaluated whether an RELN gene variant, rs362719, which has been associated with increased susceptibility to bipolar disorder, is also associated with susceptibility to schizophrenia. We included 405 Chinese Han schizophrenia patients and 390 controls in our study. The polymorphism was genotyped by PCR and RFLP methods. We found a significant difference in allele frequency distribution (P < 0.05) between schizophrenia patients and controls. The frequency of the A allele was significantly higher in schizophrenia patients than in healthy controls. The effect of SNP rs362719 on allele distribution was significant in female (P < 0.05) but not in male participants (P = 0.473). Besides the gender factor, demographic and clinical characteristics of the rs362719 genotype groups were also analyzed using the chi-square test, but no significant differences were found. We conclude that rs362719 of the RELN gene is associated with susceptibility to schizophrenia in Chinese Han, possibly through a gender-specific mechanism. Further studies will be needed to confirm this genetic risk factor for schizophrenia.

The involvement of Reelin in neurodevelopmental disorders

“…Positive associations between RELN and increased risk of schizophrenia have been identified when RELN variants have been combined with those of additional genes (Hall et al 2007) or in gender-specific manner (Ben-David et al 2010; Kuang et al 2011; Li et al 2011; Liu et al 2011; Pisanté et al 2009; Shifman et al 2008). Hall et al (2007) has demonstrated that SNPs of Reelin were associated with schizophrenia when combined with variants for additional genes, including brain-derived neurotrophic factor, neuropeptide Y, neuregulin 1, and synapsin 3, but not alone (Hall et al 2007).…”

“…Hall et al (2007) has demonstrated that SNPs of Reelin were associated with schizophrenia when combined with variants for additional genes, including brain-derived neurotrophic factor, neuropeptide Y, neuregulin 1, and synapsin 3, but not alone (Hall et al 2007). Variants of RELN have been associated with increased risk of schizophrenia for women (Ben-David et al 2010; Kuang et al 2011; Li et al 2011; Liu et al 2011; Pisanté et al 2009; Shifman et al 2008). Shifman et al (2008) found that the RELN SNP rs7341475 was associated with increased risk of schizophrenia among Ashkenazi Jewish women.…”

“…When stratified by gender, significance remained only for females, suggesting a gender-specific effect. Similarly, rs362719 has also been associated with an increased risk of schizophrenia in female but not male Han Chinese (Kuang et al 2011). …”

The relationship between attention deficit hyperactivity disorder and reelin gene polymorphisms in Turkish population

“…RELN is the most studied schizophrenia candidate gene and the findings show that RELN plays a role in disease etiology [29]. A significant relationship of rs7341475 SNP and rs362719 in female schizophrenia patients [30,31] and rs12705169 in male schizophrenia patients has been indicated [32]. RELN promoter region hypermethylation and RELN selective downregulation have been detected in postmortem schizophrenic brains [33].…”

Exploring the mRNA Expression Level of RELN in Peripheral Blood of Schizophrenia Patients Before and After Antipsychotic Treatment

“…Moreover, this gene variant was associated with working memory, episodic memory, and executive functioning in the nuclear families of one member with SCZ [21]. Subsequently, a growing number of studies have reported that a number of single nucleotide polymorphisms (SNPs) in the RELN gene were associated with the pathogenesis and/or severity of clinical symptoms of SCZ [22][23][24][25][26][27][28][29]. Hence, based on the low level of RELN in SCZ patients and the relationship between its genetic variation and SCZ, RELN may play a pathogenic role in SCZ [30].…”