Potential link between genetic polymorphisms of <em>catechol-O-methyltransferase </em>and dopamine receptors and treatment efficacy of risperidone on schizophrenia

Abstract

ObjectiveThe current study aimed to explore the association of single nucleotide polymorphisms (SNPs) within catechol-O-methyltransferase (COMT) and dopamine receptors with schizophrenia and genetic association with risperidone treatment response.MethodsA total of 690 schizophrenic patients (case group) were selected and 430 healthy people were included as the controls. All patients received risperidone treatment continuously for 8 weeks. Next, peripheral venous blood samples were collected and were subjected to polymerase chain reaction-restriction fragment length polymorphism to amplify and genotype the SNPs within COMT and dopamine receptors. Then, correlation analysis was conducted between Positive and Negative Syndrome Scale improvement rates and SNPs within COMT and the dopamine receptor gene.ResultsThe allele of DRD1 rs11749676 (A) emerged as a key element in reducing schizophrenia risk with statistical significance (P<0.001). Remarkably, alleles of COMT rs165774 (G), DRD2 rs6277 (T), and DRD3 rs6280 (C) were associated with raised predisposition to schizophrenia (all P<0.001). Regarding DRD1 rs11746641, DRD1 rs11749676, DRD2 rs6277, and DRD3 rs6280, the case group exhibited a lesser frequency of heterozygotes in comparison with wild homozygotes genotype (all P<0.001). SNPs (COMT rs4680, DRD2 rs6275, DRD2 rs1801028, and DRD2 rs6277) were remarkably associated with improvement rates of PANSS total scores (P<0.05). SNPs (COMT rs165599 and DRD2 rs1801028) were significantly associated with risperidone efficacy on negative symptoms (P<0.05).ConclusionCOMT SNPs and dopamine receptor SNPs were correlated with prevalence of schizophrenia and risperidone treatment efficacy of schizophrenia.

Association between dopamine receptor gene polymorphisms and effects of risperidone treatment: A systematic review and meta‐analysis

“…The SerSer group showed smaller percentage improvements than the SerCys group (17.0 ± 11.6 and 23.3 ± 9.9, respectively, P = 0.066). As the frequency of CysCys allele was relatively low, only the report of Han et al discussed patients carrying the CysCys mutation; the improvement in PANSS total score and negative score of seven patients was higher than that of SerSer or SerCys carriers.…”

“…Subsequently, another 304 studies were excluded after an initial review of the titles and abstracts. The full text of the remaining 85 included articles was retrieved, which encompassed 12 studies that satisfied the inclusion criteria (Figure ) . A manual search of the reference lists contained within these studies did not yield any new eligible studies.…”

“…Han et al selected 690 schizophrenic patients and studied the influence of rs11746641 and rs11749676 on the therapeutic effect of risperidone, but neither were associated with changes in the treatment efficacy of risperidone ( P = 0.060 and P = 0.086, respectively). It should be mentioned that after calculation of the WMD among the genotypes of rs11746641 T>G, we noted that unlike the TT group, the GG group experienced a slightly greater improvement in PANSS total score (WMD: 4.92, 95% CI: 1.21‐8.63, Figure D).…”

“…For Ser311Cys (rs1801028), the meta‐analysis included 806 patients in two studies . The SerSer group had a significantly lower improvement in the PANSS total score than the SerCys group (WMD: −11.58, 95% CI: −17.35 to −5.18, P < 0.0001) and in the PANSS negative score (WMD: −13.53, 95% CI: −16.53 to −10.53, P < 0.0001; Figure ).…”

“…Two articles explored the association of polymorphisms of T939C (rs6275) with effects of risperidone treatment in Chinese population. Han et al found that T939C was markedly associated with an improvement in PANSS total scores ( P < 0.001).…”