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

Shulan HE; Wuhong Tan; Sen Wang; Cuiyan WU; Pan Wang; Bin Wang; Xiaohui SU; Junjie Zhao; Xiong Guo; Youzhang Xiang

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

Author: Shulan HE ¹ ; Wuhong TAN ¹ ; Sen WANG ¹ ; Cuiyan WU ¹ ; Pan WANG ¹ ; Bin WANG ¹ ; Xiaohui SU ¹ ; Junjie ZHAO ¹ ; Xiong GUO ² ; Youzhang XIANG ³
Author Information

1. Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
2. Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China. Email: guox@mail.xjtu.edu.cn).
3. Shandong Institute for Prevention & Treatment of Endemic Disease, Jinan, Shandong 250014, China.
Publication Type:Journal Article
MeSH: ADAM Proteins; genetics; ADAMTS Proteins; Adult; Autoimmunity; genetics; physiology; Bone Morphogenetic Protein 5; genetics; Bone Morphogenetic Protein 7; genetics; Cardiomyopathies; genetics; pathology; Cell Differentiation; genetics; physiology; Chemokines, CC; genetics; Enterovirus Infections; genetics; pathology; Female; Gene Expression Profiling; HLA-D Antigens; genetics; HLA-DQ alpha-Chains; genetics; HLA-DR alpha-Chains; genetics; Humans; Male; Middle Aged; Myocytes, Cardiac; cytology; metabolism; Oligonucleotide Array Sequence Analysis; Sex Factors; Tumor Necrosis Factor Ligand Superfamily Member 15; genetics
From: Chinese Medical Journal 2014;127(1):72-78
CountryChina
Language:English
Abstract:
BACKGROUNDKeshan 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.
METHODSWe 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.
RESULTSAmong 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.
CONCLUSIONOur results might help to explain the higher susceptibility of women to this disease.