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Chinese Medical Journal
Article . 2014 . Peer-reviewed
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Genome-wide study reveals an important role of spontaneous autoimmunity, cardiomyocyte differentiation defect and antiangiogenic activities in gender-specific gene expression in Keshan disease

Authors: Shulan, He; Wuhong, Tan; Sen, Wang; Cuiyan, Wu; Pan, Wang; Bin, Wang; Xiaohui, Su; +3 Authors

Genome-wide study reveals an important role of spontaneous autoimmunity, cardiomyocyte differentiation defect and antiangiogenic activities in gender-specific gene expression in Keshan disease

Abstract

Background Keshan disease (KD) is an endemic cardiomyopathy in China. The etiology of KD is still under debate and there is no effective approach to preventing and curing this disease. Young women of child-bearing age are the most frequent victims in rural areas. The aim of this study was to determine the differences between molecular pathogenic mechanisms in male and female KD sufferers. Methods We extracted RNA from the peripheral blood mononuclear cells of KD patients (12 women and 4 men) and controls (12 women and 4 men). Then the isolated RNA was amplified, labeled and hybridized to Agilent human 4×44k whole genome microarrays. Gene expression was examined using oligonucleotide microarray analysis. A quantitative polymerase chain reaction assay was also performed to validate our microarray results. Results Among the genes differentially expressed in female KD patients we identified: HLA-DOA, HLA-DRA, and HLA-DQA1 associated with spontaneous autoimmunity; BMP5 and BMP7, involved in cardiomyocyte differentiation defect; and ADAMTS 8, CCL23, and TNFSF15, implicated in anti-angiogenic activities. These genes are involved in the canonical pathways and networks recognized for the female KD sufferers and might be related to the pathogenic mechanism of KD. Conclusion Our results might help to explain the higher susceptibility of women to this disease.

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Keywords

Adult, Male, HLA-D Antigens, Bone Morphogenetic Protein 7, Gene Expression Profiling, Autoimmunity, Cell Differentiation, HLA-DR alpha-Chains, Bone Morphogenetic Protein 5, Middle Aged, HLA-DQ alpha-Chains, ADAM Proteins, ADAMTS Proteins, Chemokines, CC, Enterovirus Infections, Humans, Female, Myocytes, Cardiac, Cardiomyopathies, Oligonucleotide Array Sequence Analysis

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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
7
Average
Average
Average
gold