Mas Sergi, Gassó Patricia, Crescenti Anna, Parellada Eduard, Bernardo Miquel, Lafuente Amalia
Departamento de Anatomía Patológica, Farmacología y Microbiología. Facultad de Medicina. Universidad de Barcelona. IDIBAPS. Barcelona. España.
Med Clin (Barc). 2008 Dec 6;131(20):761-4. doi: 10.1016/s0025-7753(08)75499-x.
Cathecol-O-methyl transferase (COMT) is one of the most plausible susceptibility genes of schizophrenia risk. The main genetic variant (G158A or rs4680) studied is functional. It has been shown that G-A transition at COMT codon 158 makes COMT more thermolabile and less active at physiological temperature. Genetic variants in the P2 promoter have been suggested to cause alterations in brain COMT protein levels. A variant in the P2 promoter (-278A/G or rs1800706) has recently been associated with psychotic disorders. We studied whether polymorphisms in COMT (G158A, -278A/G) are risk factors for schizophrenia in a Spanish population.
243 subjects diagnosed of schizophrenia and related disorders following the DSM-IV criteria and 291 hospital-based controls participated in an association study.
The heterozygotes for the COMT -278A/G polymorphism showed a 60% reduction in the schizophrenia risk (p = 0.009). No significant differences were observed between the other COMT genotypes or haplotypes in cases and controls.
Our results suggest that the COMT -278A/G polymorphism may have a role in schizophrenia. The results are in agreement with recent findings in this field that indicate a minor influence of COMT G158A on schizophrenia risk and a greater importance of polymorphisms in the P2 promoter regions of COMT, such as -278A/G.
儿茶酚-O-甲基转移酶（COMT）是精神分裂症风险最有可能的易感基因之一。所研究的主要基因变异（G158A或rs4680）具有功能性。研究表明，COMT第158位密码子的G-A转换使COMT在生理温度下更不耐热且活性更低。有人提出P2启动子中的基因变异会导致大脑中COMT蛋白水平的改变。P2启动子中的一个变异（-278A/G或rs1800706）最近与精神障碍有关。我们研究了COMT基因多态性（G158A、-278A/G）是否是西班牙人群中精神分裂症的危险因素。
243名符合《精神疾病诊断与统计手册》第四版标准诊断为精神分裂症及相关障碍的受试者和291名以医院为基础的对照者参与了一项关联研究。
COMT -278A/G多态性的杂合子显示精神分裂症风险降低了60%（p = 0.009）。病例组和对照组在其他COMT基因型或单倍型之间未观察到显著差异。
我们的结果表明，COMT -278A/G多态性可能在精神分裂症中起作用。这些结果与该领域最近的研究结果一致，即表明COMT G158A对精神分裂症风险的影响较小，而COMT P2启动子区域的多态性如-278A/G更为重要。
