Asthma-Predictive Genetic Markers in Gene Expression Profiling of Peripheral Blood Mononuclear Cells
ALLERGY ASTHMA & IMMUNOLOGY RESEARCH
Authors: Shin, Seung Woo; Oh, Tae Jeong; Park, Se-Min; Park, Jong Sook; Jang, An Soo; Park, Sung Woo; Uh, Soo Taek; An, Sungwhan; Park, Choon-Sik
Abstract
Purpose: We sought to identify asthma-related genes and to examine the potential of these genes to predict asthma, based on expression levels. Methods: The subjects were 42 asthmatics and 10 normal healthy controls. PBMC RNA was subjected to microarray analysis using a 35K array; t-tests were used to identify genes that were expressed differentially between the two groups. A multiple logistic regression analysis was applied to the differentially expressed genes, and area under the curve (AUC) values from receiver operating characteristic (ROC) curves were obtained. Results: In total, 170 genes were selected using the following criteria: P <= 0.001 and >= 2-fold change. Among these genes, 57 were up-regulated and 113 were down-regulated in asthmatics versus normal controls. A multiple logistic regression analysis was done using more stringent criteria (P <= 0.001 and >= 5-fold change), and eight genes were selected as candidate asthma biomarkers. Using these genes, 255 models (2(8)-1) were generated. Among them, only 85 showed P <= 0.05 by multiple logistic regression analysis. Based on the AUCs from ROC curves for the 85 models, we found that the best model consisted of the genes MEPE, MLSTD1, and TRIM37 The model showed 0.9928 of the AUC with 98% sensitivity and 80% specificity. Conclusions: MEPE, MLSTD1, and TRIM37 may be useful biomarkers for asthma.
Patterns of FGF-23, DMP1, and MEPE expression in patients with chronic kidney disease
BONE
Authors: Pereira, Renata C.; Juppner, Harald; Azucena-Serrano, Carlos E.; Yadin, Ora; Salusky, Isidro B.; Wesseling-Perry, Katherine
Abstract
Fibroblast growth factor 23 (FGF-23), dentin matrix protein 1 (DMP1), and matrix extracellular phosphoglycoprotein (MEPE) are skeletal proteins involved in the regulation of phosphate homeostasis and bone metabolism. Circulating FGF-23 levels are increased in patients with chronic kidney disease (CKD); however, FGF-23 skeletal expression and its regulation by DMP1 and MEPE have yet to be evaluated. Thus. expression of these three proteins was characterized by immunohistochemistry in 32 pediatric and young adult patients with CKD stages 2-5. When compared to normal controls, bone FGF-23 and DMP1 expression were increased in all stages of CKD; significant differences in bone FGF-23 and DMP1 expression were not detected between pre-dialysis CKD and dialysis patients. Bone MEPE expression in CKD did not differ from controls. FGF-23 was expressed in osteocyte cell bodies located at the trabecular periphery. DMP1 was widely expressed in osteocyte cell bodies and dendrites throughout bone. MEPE was also expressed throughout bone, but only in osteocyte cell bodies. Bone FGF-23 expression correlated directly with plasma levels of the protein (r=0.43, p<0.01) and with bone DMP1 expression (r=0.54, p<0.01) and expression of both proteins were inversely related to osteoid accumulation. Bone MEPE expression was inversely related to bone volume. In conclusion, skeletal FGF-23 and DMP1 expression are increased in CKD and are related to skeletal mineralization. The patterns of expression of FGF-23, MEPE, and DMP1 differ markedly in trabecular bone, suggesting that individual osteocytes may have specialized functions. Increases in bone FGF-23 and DMP1 expression suggest that osteocyte function is altered early in the course of CKD. (C) 2009 Elsevier Inc. All rights reserved.