Tunbridge Elizabeth, Burnet Philip W J, Sodhi Monsheel S, Harrison Paul J
Department of Psychiatry, University of Oxford, Neurosciences Building, Warneford Hospital, Oxford, OX3 7JX, UK.
Synapse. 2004 Feb;51(2):112-8. doi: 10.1002/syn.10286.
Catechol-o-methyltransferase (COMT) and proline dehydrogenase (PRODH) may both be susceptibility genes for schizophrenia. As part of the evaluation of their roles in psychosis, we used reverse transcription-polymerase chain reaction to measure COMT and PRODH mRNAs in the dorsolateral prefrontal cortex in schizophrenia, bipolar disorder, major depression, and normal controls (n = 15 subjects in each group). We also genotyped two common COMT polymorphisms (-287A/G and 158Val/Met) which might affect its expression. Neither COMT nor PRODH mRNA abundance differed between diagnostic groups, nor when controls were compared with all psychotic patients. COMT mRNA levels were unrelated to COMT genotypes. We conclude that any involvement of COMT and PRODH genes in schizophrenia is not accompanied by significant alterations in their overall mRNA expression, at least in dorsolateral prefrontal cortex. As COMT and PRODH are both located on chromosome 22q11, the results also argue against the hypothesis that schizophrenia is associated with a decrease in expression of all 22q11 genes, as had been suggested by the high prevalence of psychosis in people with hemizygous 22q11 deletions.
儿茶酚 - O - 甲基转移酶(COMT)和脯氨酸脱氢酶(PRODH)可能都是精神分裂症的易感基因。作为评估它们在精神病中作用的一部分,我们使用逆转录 - 聚合酶链反应来测量精神分裂症、双相情感障碍、重度抑郁症患者以及正常对照组(每组15名受试者)背外侧前额叶皮质中的COMT和PRODH信使核糖核酸(mRNA)。我们还对可能影响其表达的两种常见COMT多态性(-287A/G和158Val/Met)进行了基因分型。在诊断组之间,以及将对照组与所有精神病患者进行比较时,COMT和PRODH的mRNA丰度均无差异。COMT的mRNA水平与COMT基因型无关。我们得出结论,至少在背外侧前额叶皮质中,COMT和PRODH基因在精神分裂症中的任何参与都不会伴随着它们整体mRNA表达的显著改变。由于COMT和PRODH都位于22号染色体q11区域,这些结果也反驳了如下假设,即精神分裂症与所有22q11基因的表达降低有关,正如22q11半合子缺失患者中精神病的高患病率所暗示的那样。