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DAOA/G30 基因座与情感障碍:基于单体型的多诊断方法关联研究。

The DAOA/G30 locus and affective disorders: haplotype based association study in a polydiagnostic approach.

机构信息

Department of Psychiatry and Psychotherapy, University of Würzburg, Füchsleinstrasse 15, Würzburg, Germany.

出版信息

BMC Psychiatry. 2010 Jul 29;10:59. doi: 10.1186/1471-244X-10-59.

Abstract

BACKGROUND

The DAOA/G30 (D-amino acid oxidase activator) gene complex at chromosomal region 13q32-33 is one of the most intriguing susceptibility loci for the major psychiatric disorders, although there is no consensus about the specific risk alleles or haplotypes across studies.

METHODS

In a case-control sample of German descent (affective psychosis: n = 248; controls: n = 188) we examined seven single nucleotide polymorphisms (SNPs) around DAOA/G30 (rs3916966, rs1935058, rs2391191, rs1935062, rs947267, rs3918342, and rs9558575) for genetic association in a polydiagnostic approach (ICD 10; Leonhard's classification).

RESULTS

No single marker showed evidence of overall association with affective disorder neither in ICD10 nor Leonhard's classification. Haplotype analysis revealed no association with recurrent unipolar depression or bipolar disorder according to ICD10, within Leonhard's classification manic-depression was associated with a 3-locus haplotype (rs2391191, rs1935062, and rs3916966; P = 0.022) and monopolar depression with a 5-locus combination at the DAOA/G30 core region (P = 0.036).

CONCLUSION

Our data revealed potential evidence for partially overlapping risk haplotypes at the DAOA/G30 locus in Leonhard's affective psychoses, but do not support a common genetic contribution of the DAOA/G30 gene complex to the pathogenesis of affective disorders.

摘要

背景

染色体区域 13q32-33 上的 DAOA/G30(D-氨基酸氧化酶激活剂)基因复合体是主要精神疾病最引人关注的易感基因之一,尽管在不同研究中对于特定的风险等位基因或单体型尚无共识。

方法

在一个德国血统的病例对照样本中(情感性精神病:n = 248;对照组:n = 188),我们在多诊断方法(ICD-10;Leonhard 分类)中检查了 DAOA/G30 周围的七个单核苷酸多态性(SNP)(rs3916966、rs1935058、rs2391191、rs1935062、rs947267、rs3918342 和 rs9558575)与遗传相关性。

结果

没有一个单一的标记物在 ICD10 或 Leonhard 分类中显示出与情感障碍的总体关联。单体型分析显示,根据 ICD10,与复发性单相抑郁或双相障碍均无关联,根据 Leonhard 分类,躁狂-抑郁与 3 个位点单体型(rs2391191、rs1935062 和 rs3916966;P = 0.022)相关,单相抑郁与 DAOA/G30 核心区域的 5 个位点组合相关(P = 0.036)。

结论

我们的数据显示了在 Leonhard 的情感性精神病中 DAOA/G30 基因座上部分重叠的风险单体型的潜在证据,但不支持 DAOA/G30 基因复合体对情感障碍发病机制的共同遗传贡献。

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