精神分裂症与儿茶酚氧位甲基转移酶启动子甲基化状态  

Promoter methylation of catechol-O-methyl transferase gene and schizophrenia

作　　者：张璇[1] 刘铁榜[1] 吴怀安[1] 邓小敏[1] 闫小华[1] 杨孔军[1] 荣晗[1] 

机构地区：[1]深圳市精神卫生中心精神科,518020

出　　处：《中华精神科杂志》2011年第2期79-83,共5页Chinese Journal of Psychiatry

基　　金：深圳市科技计划资助项目（200802083）

摘　　要：目的探讨精神分裂症患者儿茶酚氧位甲基转移酶（COMT）基因启动子甲基化状态，并对基因多态性、启动子甲基化状态及基因表达水平与精神分裂症的关系进行探讨。方法采用聚合酶链反应（PCR）和限制性片段长度多态性技术检测精神分裂症患者（患者组，110例）及正常对照组（对照组，100名）外周血基因组中COMT的基因型，采用甲基化特异性聚合酶链反应（MSP）技术检测COMT基因的甲基化状态，采用实时定量PCR法检测COMT基因mRNA的表达。结果（1）患者组COMT基因Val／Val基因频率高于对照组（55．4％VS40．0％，P=0．025），Met／Met基因频率低于对照组（9．1％VS19．0％，P=0．038），差异有统计学意义；患者组COMT等位基因Val的频率高于对照组（73．2％VS60．5％），等位基因Met的频率低于对照组（26．8％VS39．5％），差异具有统计学意义（P=0．006，P=0．006）。（2）患者组有46例甲基化阳性，甲基化率为41．8％，对照组有51名甲基化阳性，甲基化率为51．0％，2组比较差异无统计学意义（x^2=1．777，P=0．183）；患者组COMT基因甲基化与基因型之间无关联性（x^2=0．139，P=0．933）。（3）患者组中非甲基化表型联合Val／Val型患者mRNA表达水平显著高于其他各组（F=11．408，P=0．000）。结论COMT基因多态性与精神分裂症关联，COMT基因多态性可能与甲基化状态共同作用影响基因的表达，但并不能确定COMT基因启动子甲基化状态与精神分裂症的发病有关。Objective To explore the promoter methylation of COMT gene in patients with schizophrenia, and analyze the relationships between schizophrenia and polymorphisms, promoter methylation,and expression of COMT gene. Methods One hundred and ten patients with schizophrenia and 100 healthy people were recruited. The genetic polymorphisms of COMT gene in schizophrenia and controls were measured by polymerase chain reaction and restriction fragment length polymorphism technique （PCRRFLP）. The methylated status of CpG islands of COMT were tested by methylation-specific polymerase chain reaction （MSP）, and COMT mRNA expression level was detected by real-time reverse transcription polymerase chain reaction. Results （ 1 ） The frequency of genotype of Val/Val in patients was significantly higher than that in the controls （55.4% vs. 40.0% , P = 0. 025 ）, and the frequency of genotype of Met/ Met was lower （9.1% vs. 19.0%, P =0. 038）. The frequency of allele Val in patients was significantly higher than that in the controls, and the frequency of allele Met was lower （73.2% vs. 60.5% , 26.8% vs. 39.5% , both P = 0. 006）. （2） The frequency of promoter methylation of COMT gene was 41.8% in patients and 51.0% in the controls （ X2 = 1. 777, P = 0. 183） , and no significant difference in the mRNA expression level of COMT between both groups （ t = - 0. 165, P = 0. 869 ）. No association between the promoter methylation and genotype of COMT was observed in schizophrenia patients （X2 = 0. 139, P = 0. 933 ） . （3） The schizophrenia were divided into 6 groups according to promoter methylation combined with genotype, the mRNA expression level of COMT was much higher in the ones with unmethylation combined with Val/Val genotype than other groups （F = 11. 408, P = 0. 000）. Conclusion The polymorphism of COMT is possibly associated with schizophrenia in this sample. The polymorphism combined with promoter methylation might have effects on the expression of COMT. But it is not confirmd that the COMT

关 键 词：精神分裂症 甲基化 多态性 限制性片段长度 基因表达 儿茶酚氧位甲基 转移酶 

分 类 号：R749.3[医药卫生—神经病学与精神病学]