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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2009-3-23
pubmed:abstractText
RGS2 (regulator of G-protein signaling 2) modulates dopamine receptor signal transduction. Functional variants in the gene may influence susceptibility to extrapyramidal symptoms (EPS) induced by antipsychotic drugs. To further investigate our previous report of association of the RGS2 gene with susceptibility to antipsychotic-induced EPS, we performed a replication study. EPS were rated in 184 US patients with schizophrenia (115 African Americans, 69 Caucasian) treated for at least a month with typical antipsychotic drugs (n=45), risperidone (n=46), olanzapine (n=50) or clozapine (n=43). Six single nucleotide polymorphisms (SNPs) within or flanking RGS2 were genotyped (rs1933695, rs2179652, rs2746073, rs4606, rs1819741 and rs1152746). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression. Our results indicate association of SNP rs4606 with antipsychotic-induced parkinsonism (AIP), as measured by the Simpson Angus scale, in the overall sample and in the African-American subsample, the G (minor) allele having a protective effect. ORs for AIP among rs4606 G-allele carriers were 0.23 (95% CI 0.10-0.54, P=0.001) in the overall sample, and 0.20 (0.07-0.57, P=0.003) in the African-American subsample. In the previously studied Israeli sample the OR was 0.31 (0.11-0.84, P=0.02). We completely sequenced the RGS2 gene in nine patients with AIP and nine patients without, from the Israeli sample. No common coding polymorphisms or additional regulatory variants were revealed, suggesting that association of the rs4606 C/G polymorphism with AIP is biologically meaningful and not a consequence of linkage disequilibrium with another functional variant. Taken together, the findings of the current study support the association of RGS2 with AIP and focus on a possible protective effect of the minor G allele of SNP rs4606. This SNP is located in the 3'-regulatory region of the gene, and is known to influence RGS2 mRNA levels and protein expression.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1473-1150
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
103-10
pubmed:meshHeading
pubmed-meshheading:18347610-3' Untranslated Regions, pubmed-meshheading:18347610-Adult, pubmed-meshheading:18347610-African Americans, pubmed-meshheading:18347610-Antipsychotic Agents, pubmed-meshheading:18347610-Cross-Sectional Studies, pubmed-meshheading:18347610-DNA Mutational Analysis, pubmed-meshheading:18347610-European Continental Ancestry Group, pubmed-meshheading:18347610-Female, pubmed-meshheading:18347610-Gene Frequency, pubmed-meshheading:18347610-Genetic Predisposition to Disease, pubmed-meshheading:18347610-Haplotypes, pubmed-meshheading:18347610-Humans, pubmed-meshheading:18347610-Israel, pubmed-meshheading:18347610-Logistic Models, pubmed-meshheading:18347610-Male, pubmed-meshheading:18347610-Odds Ratio, pubmed-meshheading:18347610-Parkinson Disease, Secondary, pubmed-meshheading:18347610-Polymorphism, Single Nucleotide, pubmed-meshheading:18347610-RGS Proteins, pubmed-meshheading:18347610-Risk Assessment, pubmed-meshheading:18347610-Risk Factors, pubmed-meshheading:18347610-Schizophrenia, pubmed-meshheading:18347610-United States
pubmed:year
2009
pubmed:articleTitle
Further evidence for association of the RGS2 gene with antipsychotic-induced parkinsonism: protective role of a functional polymorphism in the 3'-untranslated region.
pubmed:affiliation
Biological Psychiatry Laboratory, Department of Psychiatry, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't