Gene expression profiling in monocytes and SNP association suggest the importance of the STAT1 gene for osteoporosis in both Chinese and Caucasians.
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.
Chen
Xiang-Ding
XD
Laboratory 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.
Xiao
Peng
P
Lei
Shu-Feng
SF
Liu
Yao-Zhong
YZ
Guo
Yan-Fang
YF
Deng
Fei-Yan
FY
Tan
Li-Jun
LJ
Zhu
Xue-Zhen
XZ
Chen
Fu-Rong
FR
Recker
Robert R
RR
Deng
Hong-Wen
HW
D000328:Adult; D000367:Age Factors; D000368:Aged; D044466:Asian People / Q000235:genetics*; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D010024:Osteoporosis / Q000235:genetics* / Q000503:physiopathology; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D015854:Up-Regulation; D044465:White People / Q000235:genetics*
D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human