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KMID : 1034820120080030297
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Molecular & Cellular Toxicology
2012 Volume.8 No. 3 p.297 ~ p.302
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Association between a synonymous SNP (rs470558, Ala216Ala) of MMP1 and schizophrenia with auditory hallucinations in Korean population
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Kim Jong-Woo
Kang Won-Sub
Lee Sang-Min
Kim Su-Kang
Park Hae-Jeong
Gwak Geum-Hee
Baik Hyung-Hwan
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Abstract
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Extracellular matrix (ECM) abnormality is implicated in the pathogenesis of schizophrenia. Matrix metalloproteinases (MMPs) mediate the proteolysis of ECM and may play a crucial role in neuronal plasticity. We investigated whether single nucleotide polymorphisms (SNPs) of MMP1 and MMP8 are associated with the development of schizophrenia. We also assessed the relationships between MMP1, MMP8 SNPs and the core symptoms of schizophrenia such as persecutory delusion, auditory hallucinations, affective disturbances, and poor concentration according to the Operation Criteria Checklist for Psychotic Illness (OPCRIT). Three coding SNPs (rs470558, Ala216Ala in MMP1; rs3740938, Leu291Leu and rs1940475, Lys87Glu in MMP8) were selected, and 263 patients and 283 controls were evaluated. SNPStats was used to obtain the odds ratio (OR), 95% confidence intervals (CI), and P value adjusted for age and gender as covariables. Multiple logistic regression models (codominant1, codominant2, dominant, recessive, and log-additive) were employed to analyze genetic data. As a result, the three examined SNPs were not associated with the development of schizophrenia. In the analysis of clinical symptoms, the genotype frequency of rs470558 in MMP1 was associated with auditory hallucinations (P=0.04 in the codominant1 model, P=0.014 in the dominant1 model, and P=0.0066 in the log-additive model). The allele frequency of rs470558 also showed a significant difference between schizophrenia without auditory hallucinations [the auditory hallucination (?) group] and schizophrenia with auditory hallucinations [the auditory hallucination (+) group] (P=0.009, OR= 1.94, 95% CI=1.19-3.28). The A allele frequency of rs470558 was higher in the auditory hallucination (+) group (19.2%) than that in the auditory hallucination (?) group (10.8%). Two MMP8 SNPs (rs3740938 and rs1940475) were not associated with the development and core symptoms of schizophrenia, respectively. These results suggest that the A allele of rs470558 (Ala216Ala) in MMP1 may contribute to the susceptibility to auditory hallucinations of schizophrenia.
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KEYWORD
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Auditory hallucinations, ECM abnormality, MMP1, MMP8, Schizophrenia, Single nucleotide polymorphism
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