ABSTRACT
<p><b>BACKGROUND</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>Our results might help to explain the higher susceptibility of women to this disease.</p>
Subject(s)
Adult , Female , Humans , Male , Middle Aged , ADAM Proteins , Genetics , ADAMTS Proteins , 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 , Gene Expression Profiling , HLA-D Antigens , Genetics , HLA-DQ alpha-Chains , Genetics , HLA-DR alpha-Chains , Genetics , Myocytes, Cardiac , Cell Biology , Metabolism , Oligonucleotide Array Sequence Analysis , Sex Factors , Tumor Necrosis Factor Ligand Superfamily Member 15 , GeneticsABSTRACT
PURPOSE:The cone-shaped epiphyses mid-5 (CSE-5) and brachymesophalagia-5 (BMP-5) are common osseous anomalies. Those are thought to be normal variants. We evaluated the frequency of CSE-5 and BMP-5 and the influence of them on adult height in Korean children with normal short stature. METHODS:We retrospectively reviewed medical records of 322 normal short stature children. Lengths of the fourth (MP-4) and fifth middle phalanx (MP-5) and widths of MP-5 of all children were measured. Two indicies for BMP-5 were used. Index 1 was based upon the ratio of the width to the length of the MP-5. Index 2 was based upon the ratio of the lengths of MP-5 to MP-4. CSE-5 was assessed by visual inspection only. We assessed several clinical parameters as follows; advanced skeletal maturation, z-scores of height, target height (THz) and predicted adult height (PAHz) according to CSE-5 and/or BMP-5. Results:Of the 322 children, 23.6% had BMP-5 (male 19.5%, female 27.4%), 23.6% had CSE-5 (male 13.0%, female 33.3%). The children with CSE-5 and/or BMP-5 were more advanced skeletal maturation than normal fifth finger (0.07+/-1.09 yrs vs -0.23+/-1.34 yrs, P=0.049), lower PAHz (-1.13+/-1.09 vs -0.71+/-1.28, P=0.008), lower PAHz- THz (-0.53+/-1.07 vs -0.14+/-1.30, P=0.013). In male subjects, the PAHz had weak correlation with index 1 (r=-0.26, P=0.001) and index 2 (r=0.27, P=0.001). CONCLUSION:This study suggests that BMP-5 and CSE-5 in Korean children with short stature are one contributable factor for adult height.