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No evidence for association between polymorphisms in GRM3 and schizophrenia.

ABSTRACT: Three studies have previously reported data that were interpreted by the authors as supportive of association between schizophrenia and polymorphisms in the gene encoding the metabotropic glutamate receptor GRM3.In a bid to examine this hypothesis, we examined seven SNPs spanning GRM3 in a UK case-control sample (schizophrenic cases n = 674, controls n = 716). These included all SNPs previously reported to be associated, alone or in haplotypes, with schizophrenia in European or European American samples.Our data showed no evidence for association with single markers, or 2, 3, 4 and 5 marker haplotypes, nor did any specific haplotypes show evidence for association according to previously observed patterns.Examination of our own data and those of other groups leads us to conclude that at present, GRM3 should not be viewed as a gene for which there is replicated evidence for association with schizophrenia.

SUBMITTER: Norton N

PROVIDER: S-EPMC1142331 | biostudies-literature | 2005 May

REPOSITORIES: biostudies-literature

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No evidence for association between polymorphisms in GRM3 and schizophrenia.

Norton Nadine N Williams Hywel J HJ Dwyer Sarah S Ivanov Dobril D Preece Anna C AC Gerrish Amy A Williams Nigel M NM Yerassimou Pamela P Zammit Stanley S O'Donovan Michael C MC Owen Michael J MJ

BMC psychiatry 20050513

<h4>Background</h4>Three studies have previously reported data that were interpreted by the authors as supportive of association between schizophrenia and polymorphisms in the gene encoding the metabotropic glutamate receptor GRM3.<h4>Methods</h4>In a bid to examine this hypothesis, we examined seven SNPs spanning GRM3 in a UK case-control sample (schizophrenic cases n = 674, controls n = 716). These included all SNPs previously reported to be associated, alone or in haplotypes, with schizophren ...[more]

PMID: 15892884

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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.

Dataset Information

No evidence for association between polymorphisms in GRM3 and schizophrenia.

Publications

No evidence for association between polymorphisms in GRM3 and schizophrenia.

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