Decreased expression of B cell related genes in leukocytes of women with Parkinson's disease.

Decreased expression of B cell related genes in leukocytes of women with Parkinson's disease.
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DOI:
10.1186/1750-1326-6-66
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发表时间:
2011-09-23
影响因子:
15.1
通讯作者:
Orr-Urtreger A
Orr-Urtreger A
中科院分区:
医学1区
文献类型:
--
作者:
Kedmi M;Bar-Shira A;Gurevich T;Giladi N;Orr-Urtreger A

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帕金森病(PD)是一种由遗传、环境和年龄相关因素引起的复杂疾病,在男性中更为普遍。我们旨在鉴定外周血白细胞(PBLs)中可能参与PD发病机制的差异表达基因。使用GeneChip Human Exon 1.0 ST阵列分析了30名女性pd患者和29名年龄和性别匹配的对照组的转录组。样本来自无血缘关系的德系犹太人个体,非LRRK2 G2019S或GBA创始人突变携带者。在115个基因(206个外显子)中检测到差异表达,免疫应答注释的过度表达。30个基因与B细胞功能相关,包括B细胞唯一表达的IGHM和IGHD, B细胞表面分子CD19、CD22和CD79A,以及B细胞基因调节因子PAX5。定量rt - pcr证实这6个基因在79个个体中表达降低,主要发生在女性患者中,与pd药物治疗状态无关。我们的研究结果表明,与B细胞活性相关的基因下调反映了这些细胞参与德系犹太人帕金森病,并代表了帕金森病性别特异性的分子方面。
Parkinson's disease (PD) is a complex disorder caused by genetic, environmental and age-related factors, and it is more prevalent in men. We aimed to identify differentially expressed genes in peripheral blood leukocytes (PBLs) that might be involved in PD pathogenesis. Transcriptomes of 30 female PD-patients and 29 age- and sex-matched controls were profiled using GeneChip Human Exon 1.0 ST Arrays. Samples were from unrelated Ashkenazi individuals, non-carriers of LRRK2 G2019S or GBA founder mutations. Differential expression was detected in 115 genes (206 exons), with over-representation of immune response annotations. Thirty genes were related to B cell functions, including the uniquely B cell-expressed IGHM and IGHD, the B cell surface molecules CD19, CD22 and CD79A, and the B cell gene regulator, PAX5. Quantitative-RT-PCR confirmation of these 6 genes in 79 individuals demonstrated decreased expression, mainly in women patients, independent of PD-pharmacotherapy status. Our results suggest that the down regulation of genes related to B cell activity reflect the involvement of these cells in PD in Ashkenazi individuals and represents a molecular aspect of gender-specificity in PD.
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