Genome-wide study reveals an important role of spontaneous autoimmunity, cardiomyocyte differentiation defect and antiangiogenic activities in gender-specific gene expression in Keshan disease
pmid: 24384427
Genome-wide study reveals an important role of spontaneous autoimmunity, cardiomyocyte differentiation defect and antiangiogenic activities in gender-specific gene expression in Keshan disease
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.
- Xi’an Jiaotong-Liverpool University China (People's Republic of)
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
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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