| Background:Schizophrenia is a complex multifactorial disorder with a worldwide lifetime prevalence of 1%.Particular attention has been focused on dopamine type D2 receptors(DRD2) due to the fact that they are the primary targets for some neuroleptic drugs.Polymorphisms of DRD2 have repeatedly been associated with schizophrenia; however,ethnic disparity seems to be a confounding factor in disease association.Objective:1) To examine the association between the high heterozogosity SNPs of DRD2 gene screened from the previous work and schizophrenia in a larger sample from the Northern Chinese population.2) To explore the association of SNP(s) with certain phenotypes scaled by PANSS grading system.3) To specify the haplotypes within DRD2 that influences risk for schizophrenia.Methods:We investigated the association of 10 polymorphisms,including -141C ins/del(rs1799732),Ser311Cys(rs1801028),His313His(rs6277),Pro319Pro(rs6275) in the DRD2 with schizophrenia using a case-control study,in 512 patients with DSM-IV diagnosis of paranoid schizophrenia and 480 unrelated mentally healthy controls.For quantitative trait analysis,we further stratified the patients by their phenotypes according to PANSS scale.Results:1) In allelic and genotypic studies,no association of 10 polymorphisms with schizophrenia or any of its symptoms was found.2) In haplotypic study,haplotypes containing rs2511521(C)-rs6275(C) were associated with the disease,specifically in males(p＜0.001).3) The quantitative trait analysis revealed that haplotypes in DRD2 are associated with most of the positive syndromes of schizophrenia.Conclusion:Our findings suggest that the haplotypes in DRD2 gene may associate with schizophrenia,and gender factor may take part in the pathogenesis of schizophrenia.A causal variant(s) in DRD2 remains to be elucidated by further fine mapping of the gene, with particular attention given to the area surrounding the fourth intron through seventh exons.
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