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Association study between polymorphisms of the PARD3 gene and schizophrenia.

ABSTRACT: The aim of this study was to investigate whether par-3 partitioning defective 3 homolog (C. elegans) (PARD3) single nucleotide polymorphisms (SNPs) are associated with schizophrenia. A total of 204 Korean schizophrenic patients [117 male, 41.1±9.6 years (mean age ± SD); 87 female, 42.6±11.5] and 351 control subjects (170 male, 43.8±6.6 years; 181 female, 44.2±5.8) were enrolled. We genotyped nine SNPs of the PARD3 gene [rs7075263 (intron), rs10827392 (intron), rs773970 (intron), rs2252655 (intron), rs10763984 (intron), rs3781128 (Ser889Ser), rs1936429 (intron), rs671228 (intron) and rs16935163 (intron)]. Genotypes of PARD3 polymorphisms were evaluated by direct sequencing. We used SNPStats, SPSS 18.0 and Haploview 4.2 software for analysis of genetic data. Multiple logistic regression models were used to calculate the odds ratio (OR), 95% confidence interval (CI), and corresponding p-values (p), controlling for age and gender as covariables. Allele frequencies of the PARD3 SNPs were significantly associated with schizophrenia (rs3781128, p=0.041; rs1936429, p=0.030; rs671228, p=0.028). Certain genotype frequencies of the PARD3 SNPs also showed significant associations with schizophrenia (p<0.05, rs7075263, rs773970, rs2252655, rs10763984, rs3781128, rs1936429, rs16935163). To the best of our knowledge, this is the first report showing that PARD3 is associated with susceptibility to schizophrenia in a Korean population. In conclusion, our findings suggest that PARD3 may contribute to genetic susceptibility to schizophrenia.

SUBMITTER: Kim SK

PROVIDER: S-EPMC3438842 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature

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Association study between polymorphisms of the PARD3 gene and schizophrenia.

Kim Su Kang SK Lee Jong Yoon JY Park Hae Jeong HJ Kim Jong Woo JW Chung Joo-Ho JH

Experimental and therapeutic medicine 20120223 5

The aim of this study was to investigate whether par-3 partitioning defective 3 homolog (C. elegans) (PARD3) single nucleotide polymorphisms (SNPs) are associated with schizophrenia. A total of 204 Korean schizophrenic patients [117 male, 41.1±9.6 years (mean age ± SD); 87 female, 42.6±11.5] and 351 control subjects (170 male, 43.8±6.6 years; 181 female, 44.2±5.8) were enrolled. We genotyped nine SNPs of the PARD3 gene [rs7075263 (intron), rs10827392 (intron), rs773970 (intron), rs2252655 (intro ...[more]

PMID: 22969987

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Project description:Schizophrenia (SZ) is a multifactorial and neurodegenerative disorder that results from the interaction between genetic and environmental factors. Notably, hundreds of single nucleotide polymorphisms (SNPs) are associated with the susceptibility to SZ. Vitamin D (VD) plays an essential role in regulating several genes important for maintaining brain function and health. To the best of the authors' knowledge, no studies have yet been conducted on the association between the VD pathway and patients with SZ. Therefore, the present study aimed to assess the potential association between eight SNPs in genes related to the VD pathway, including CYP2R1, CYP27B1, CYP24A1 and VDR among patients with SZ. A case-control study was conducted, involving a total of 400 blood samples drawn from 200 patients and 200 healthy controls. Genomic DNA was extracted and variants were genotyped using the tetra-amplification refractory mutation system-polymerase chain reaction method. The present study revealed statistically significant differences between patients with SZ and controls regarding the genotypes and allele distributions of three SNPs [CYP2R1 (rs10741657), CYP27B1 (rs10877012) and CYP24A1 (rs6013897) (P<0.0001)]. The AA genotype of rs10741657 was identified to be associated with SZ (P<0.0001) and the frequency of the A allele was higher in patients with SZ (P<0.0001) compared with the control group. Similarly, the TT genotype of rs10877012 was revealed to be associated with SZ (P<0.0001) and the T allele was more frequent in patients with SZ (P<0.0001) than in the control group. Moreover, the AA genotype of rs6013897 was revealed to be associated with SZ (P<0.0001), although no significant difference was detected between the two groups regarding the A allele (P=0.055). VDR (rs2228570, rs1544410, rs731236 and rs7975232) and CYP27B1 (rs4646536) gene polymorphisms did not exhibit a significant association with SZ. While the studied SNPs revealed promising discriminatory capacity between patients with SZ and controls, the rs10741657 SNP exhibited the most optimal area under the curve value at 0.615. A logistic model was applied considering only the significant SNPs and VD levels, which revealed that rs6013897 (T/A) and VD may have protective effects (0.267, P<0.001; 0.888, P<0.001, respectively). Moreover, a low serum VD level was highly prevalent in patients with SZ compared with the controls. Based on this finding, an association between serum 25(OH)D and SZ could be demonstrated. The present study revealed that CYP2R1 (rs10741657), CYP27B1 (rs10877012) and CYP24A1 (rs6013897) gene SNPs may be associated with SZ susceptibility.

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Association study between polymorphisms of the PARD3 gene and schizophrenia.

Publications

Association study between polymorphisms of the PARD3 gene and schizophrenia.

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