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KMID : 1034820090050020160
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Molecular & Cellular Toxicology
2009 Volume.5 No. 2 p.160 ~ p.164
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Association Analysis between Polymorph isms of NOTCH4 Gene and Schizophrenia in Korean Population
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Lee Seo-Kyong
Kang Sung-Wook
Kim Su-Kang
Kim Hak-Jae
Kim Tae
Park Jin-Kyoung
Cho Ah-Rang
Kim Jong-Woo
Park Hyun-Kyung
Kim Youn-Jung
Choe Bong-Keun
Song Ji-Young
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Abstract
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Notch signaling plays a crucial role in development of the nervous system. Neurodevelopmental hypothesis on etiology of schizophrenia has been implicated. The aim of this study is to determine whether single nucleotide polymorphisms (SNPs) of Notch homolog 4 (Drosophila) (NOTCH4) gene are associated with schizophrenia. This study included 283 schizophrenia patients diagnosed according to DSM-IV and 301 normal control subjects. Control subjects without history of psychiatric disorders were recruited. Four missense SNPs [rs915894 (exon 3, Lys117Gln), rs2071282 (exon 4, Pro204Leu), rs422951 (exon 6, Thr320Ala), and rs17604492 (exon 18, Gly942Arg)] of NOTCH4 gene were genotyped by the direct sequencing method. Multiple logistic regression models (codominant, dominant, and recessive models) were employed to evaluate odds ratio, 95% confidence interval, and p value. For analysis of genetic data, SNPStats, Haploview, HapAnalyzer, SNPAnalyzer, and Helixtree programs were also used. Of 4 SNPs, rs2071282 was weekly associated with schizophrenia in two alternative models (codominant model, P=0.049; dominant, P=0.041). However, these associations were not significant after Bonferroni correction. At 4 SNPs, one linkage disequilibrium (LD) block was made. This block consisted of rs915894 and rs2071282. In haplotype analysis, AC haplotype was weakly associated with schizophrenia (dominant, P=0.04). This association was disappeared after Bonferroni correction. Our result shows possibility that some SNPs of NOTCH4 gene may be weekly associated with development of schizophrenia in Korean population. However, replication result by other population will be needed.
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KEYWORD
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NOTCH4, Schizophrenia, Polymorphism, Haplotype, Association
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