偏执型精神分裂症与4个涉及多巴胺代谢的基因之间的关联分析

An Association Study Between Paranoid Schizophrenia and Four Genes Involved in Dopamine Metabolism

精神分裂症是由多基因相互作用导致的复杂疾病。对其易感基因,儿茶酚氧位甲基转移酶基因(COMT)的众多报道充满了矛盾。在对偏执型精神分裂症研究中,我们用多基因座关联分析法研究了4个涉及神经递质多巴胺代谢的基因之间的相互作用。分析结果支持如下假说:COMT-136-BclⅠ对Val108/158Met有调控作用。当前者的基因型是CC时,后者的易感等位基因型是Met(A);而当前者的基因型是GG时,后者的易感等位基因型是Val(G)。这一新的假说可以解释此前单基因座分析对Val108/158Met(COMT)的截然相反的报道,同时也显示了多基因座分析对复杂疾病研究的必要性。

Schizophrenia is a complex disease caused by interactions among multiple genes. Reports of one of its susceptibility genes, ethyltracatechol-O-mnsferase （COMT） have been conflicting. In the present study on paranoid schizophrenia, we have performed a multilocus association study to analyze the interactions among 4 genes that are involved in dopamine metabolism. Result supports the hypothesis that COMT-136-Bcl Ⅰ regulates Val^108/158 Met. When the genotype of the former is CO, Met （A） is the genotype of susceptibility allele Val^108/158 Met; and when the genotype of the former is GG, Val （G） is the genotype of susceptibility allele Val^108/1588 Met. This new hypothesis may explain the conflicting results about Val^108/158 Met （COMT） obtained by single-locus analyses, It also illustrates that multilocus analysis is necessary for the research of complex diseases.