Variants in the catechol-o-methyltransferase (COMT) gene are associated with schizophrenia in Irish high-density families
Variants in the catechol-o-methyltransferase (COMT) gene are associated with schizophrenia in Irish high-density families
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DOI：
10.1038/sj.mp.4001519
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发表时间：
2004-10-01
影响因子：
11
通讯作者：
Kendler, KS
中科院分区：
文献类型：
--
作者：
Chen, X;Wang, X;Kendler, KS
儿茶酚-O-甲基转移酶（COMT）将甲基从腺苷甲硫氨酸转移到包括神经递质多巴胺、肾上腺素和去甲肾上腺素在内的儿茶酚胺。这种甲基化导致儿茶酚胺的降解。COMT基因参与这些神经递质的代谢途径，使其成为许多精神疾病的有吸引力的候选基因。在这篇文章中，我们报告了我们的研究，COMT与精神分裂症的爱尔兰家庭与高密度的精神分裂症。三个单核苷酸多态性（SNPs）的基因分型的274个家庭和家庭内传播不平衡检验进行。SNP rs 4680是功能性瓦尔/Met多态性，通过TRANSMIT、FBAT和PDT程序显示与疾病适度相关，而其他两个SNP均为阴性。这些SNP在爱尔兰受试者中的LD水平低于德系犹太人。单倍型分析表明，单倍型，单倍型A-G-A SNPs rs737865-rs 4680-rs 165599，优先传递给受影响的主题。这与在德系犹太人中发现的G-G-G单倍型不同，但两种单倍型都有瓦尔等位基因。我们的结论是，COMT基因与精神分裂症，并进行了一个小的，但显着的风险，在爱尔兰的主题的易感性。
The enzyme catechol-o-methyltransferase (COMT) transfers a methyl group from adenosylmethionine to catecholamines including the neurotransmitters dopamine, epinephrine and norepinephrine. This methylation results in the degradation of catecholamines. The involvement of the COMT gene in the metabolic pathway of these neurotransmitters has made it an attractive candidate gene for many psychiatric disorders. In this article, we reported our study of association of COMT with schizophrenia in Irish families with a high density of schizophrenia. Three single nucleotide polymorphisms (SNPs) were genotyped for the 274 such families and within-family transmission disequilibrium tests were performed. SNP rs4680, which is the functional Val/Met polymorphism, showed modest association with the disease by the TRANSMIT, FBAT and PDT programs, while the other two SNPs were negative. These SNPs showed lower level of LDs with each other in the Irish subjects than in Ashkenazi Jews. Haplotype analysis indicated that a haplotype, haplotype A-G-A for SNPs rs737865-rs4680-rs165599, was preferentially transmitted to the affected subjects. This was different from the reported G-G-G haplotype found in Ashkenazi Jews, but both haplotypes shared the Val allele. We concluded that COMT gene is associated with schizophrenia and carries a small but significant risk to the susceptibility in the Irish subjects.