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二胺氧化酶与G72(DAOA)/G30基因与双相情感障碍的关联。

Association of DAO and G72(DAOA)/G30 genes with bipolar affective disorder.

作者信息

Prata Diana, Breen Gerome, Osborne Sarah, Munro Janet, St Clair David, Collier David

机构信息

Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, London, UK.

出版信息

Am J Med Genet B Neuropsychiatr Genet. 2008 Sep 5;147B(6):914-7. doi: 10.1002/ajmg.b.30682.

Abstract

There is growing evidence of partial aetiological overlap between schizophrenia and bipolar disorder (BP) from linkage analysis, genetic epidemiology and molecular genetics studies. In the present study we investigated whether individual polymorphisms or haplotypes of the DAO and G72(DAOA)/G30 genes, which have been previously implicated in schizophrenia, are also associated with bipolar disorder. For each gene, we genotyped 213 cases and 197 controls for SNPs previously associated with schizophrenia: rs2111902 (MDAAO-4), rs3918346 (MDAAO-5), rs3741775 (MDAAO-6) and rs3918347 (MDAAO-7) in DAO and rs746187 (M7), rs3916966 (M13), rs2391191 (M15) and rs3916972 (M25) in G72. Although none of the individual SNPs in these genes reached statistical significance, we found haplotype wise associations with bipolar disorder for both genes. These included a two-SNP haplotype in DAO (rs2111902-A and rs3918346-T; global P = 0.003, individual P = 0.002, Z = 3.1) and a two-SNP haplotype for G72(DAOA)/G30 (rs746187-G and rs3916972-G; global P = 0.05; individual P = 0.005, Z = 2.81). However, we found no evidence for an epistatic interaction between the SNPs and/or haplotypes of the two genes. In summary, our findings provide some support for the individual involvement of DAO and G72(DAOA)/G30 in the etiology of bipolar disorder.

摘要

来自连锁分析、遗传流行病学和分子遗传学研究的证据越来越多地表明,精神分裂症和双相情感障碍(BP)之间存在部分病因重叠。在本研究中,我们调查了先前与精神分裂症有关的DAO和G72(DAOA)/G30基因的个体多态性或单倍型是否也与双相情感障碍有关。对于每个基因,我们对213例双相情感障碍患者和197名对照进行了先前与精神分裂症相关的单核苷酸多态性(SNP)基因分型:DAO基因中的rs2111902(MDAAO - 4)、rs3918346(MDAAO - 5)、rs3741775(MDAAO - 6)和rs3918347(MDAAO - 7),以及G72基因中的rs746187(M7)、rs3916966(M13)、rsj2391191(M15)和rs3916972(M25)。虽然这些基因中的单个SNP均未达到统计学显著性,但我们发现这两个基因的单倍型与双相情感障碍存在关联。这些关联包括DAO基因中的一个双SNP单倍型(rs2111902 - A和rs3918346 - T;整体P = 0.003,个体P = 0.002,Z = 3.1)以及G72(DAOA)/G30基因中的一个双SNP单倍型(rs746187 - G和rs3916972 - G;整体P = 0.05;个体P = 0.005,Z = 2.81)。然而,我们没有发现这两个基因的SNP和/或单倍型之间存在上位性相互作用的证据。总之,我们的研究结果为DAO和G72(DAOA)/G30分别参与双相情感障碍的病因提供了一些支持。

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