Article :: Gene expression profiling in monocytes and SNP association suggest the importance of the STAT1 gene for osteoporosis in both Chinese and Caucasians

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Original Article

Gene expression profiling in monocytes and SNP association suggest the importance of the STAT1 gene for osteoporosis in both Chinese and Caucasians

Xiang-Ding Chen^{1 2}, Peng Xiao², Shu-Feng Lei¹, Yao-Zhong Liu³, Yan-Fang Guo¹, Fei-Yan Deng¹, Li-Jun Tan¹, Xue-Zhen Zhu¹, Fu-Rong Chen¹, Robert R. Recker², Hong-Wen Deng^{1 3 *}

¹Laboratory of Molecular and Statistical Genetics and Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha, Hunan, Peoples Republic of China
²Osteoporosis Research Center and Department of Biomedical Sciences, Creighton University Medical Center, Omaha, NE, USA
³Departments of Orthopedic Surgery and Basic Medical Sciences, University of Missouri-Kansas City, Kansas City, MO, USA

email: Hong-Wen Deng (dengh@umkc.edu)

^*Correspondence to Hong-Wen Deng, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, Peoples Republic of China.

Keywords

STAT1 bmd monocytes osteoporosis microarray SNP

Abstract

Osteoporosis is characterized mainly by low bone mineral density (BMD). Many cytokines and chemokines have been related with bone metabolism. Monocytes in the immune system are important sources of cytokines and chemokines for bone metabolism. However, no study has investigated in vivo expression of a large number of various factors simultaneously in human monocytes underlying osteoporosis. This study explored the in vivo expression pattern of general cytokines, chemokines, and their receptor genes in human monocytes and validated the significant genes by qRT-PCR and genetic association analyses. Expression profilings were performed in monocyte samples from 26 Chinese and 20 Caucasian premenopausal women with discordant BMD. Genome-wide association analysis with BMD variation was conducted in 1000 unrelated Caucasians. We selected 168 cytokines, chemokines, osteoclast-related factors, and their receptor genes for analyses. Significantly, the signal transducer and activator of transcription 1 (STAT1) gene was upregulated in the low versus the high BMD groups in both Chinese and Caucasians. We also revealed a significant association of the STAT1 gene with BMD variation in the 1000 Caucasians. Thus we conclude that the STAT1 gene is important in human circulating monocytes in the etiology of osteoporosis. © 2010 American Society for Bone and Mineral Research

Received: 24 October 2008; Revised: 14 January 2009; Accepted: 6 July 2009

Digital Object Identifier (DOI)

10.1359/jbmr.090724 About DOI