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SNP rs6265 Regulates Protein Phosphorylation and Osteoblast Differentiation and Influences BMD in Humans
Journal of bone and mineral research, 2013-12, Vol.28 (12), p.2498-2507
Deng, Fei‐Yan
Tan, Li‐Jun
Shen, Hui
Liu, Yong‐Jun
Liu, Yao‐Zhong
Li, Jian
Zhu, Xue‐Zhen
Chen, Xiang‐Ding
Tian, Qing
Zhao, Ming
Deng, Hong‐Wen
2013
Details
Autor(en) / Beteiligte
Deng, Fei‐Yan
Tan, Li‐Jun
Shen, Hui
Liu, Yong‐Jun
Liu, Yao‐Zhong
Li, Jian
Zhu, Xue‐Zhen
Chen, Xiang‐Ding
Tian, Qing
Zhao, Ming
Deng, Hong‐Wen
Titel
SNP rs6265 Regulates Protein Phosphorylation and Osteoblast Differentiation and Influences BMD in Humans
Ist Teil von
Journal of bone and mineral research, 2013-12, Vol.28 (12), p.2498-2507
Ort / Verlag
United States: Wiley Subscription Services, Inc
Erscheinungsjahr
2013
Link zum Volltext
Quelle
MEDLINE
Beschreibungen/Notizen
ABSTRACT Bone mineral density (BMD) is a major index for diagnosing osteoporosis. PhosSNPs are nonsynonymous SNPs that affect protein phosphorylation. The relevance and significance of phosSNPs to BMD and osteoporosis is unknown. This study aimed to identify and characterize phosSNPs significant for BMD in humans. We conducted a pilot genomewide phosSNP association study for BMD in three independent population samples, involving ∼5000 unrelated individuals. We identified and replicated three phosSNPs associated with both spine BMD and hip BMD in Caucasians. Association with hip BMD for one of these phosSNPs, ie, rs6265 (major/minor allele: G/A) in BDNF gene, was also suggested in Chinese. Consistently in both ethnicities, individuals carrying the AA genotype have significantly lower hip BMD than carriers of the GA and GG genotypes. Through in vitro molecular and cellular studies, we found that compared to osteoblastic cells transfected with wild‐type BDNF‐Val66 (encoded with allele G at rs6265), transfection of variant BDNF‐Met66 (encoded with allele A at rs6265) significantly decreased BDNF protein phosphorylation (at amino acid residue T62), expression of osteoblastic genes (OPN, BMP2, and ALP), and osteoblastic activity. The findings are consistent with and explain our prior observations in general human populations. We conclude that phosSNP rs6265, by regulating BDNF protein phosphorylation and osteoblast differentiation, influences hip BMD in humans. This study represents our first endeavor to dissect the functions of phosSNPs in bone, which might stimulate extended large‐scale studies on bone or similar studies on other human complex traits and diseases. © 2013 American Society for Bone and Mineral Research.
Sprache
Englisch
Identifikatoren
ISSN: 0884-0431
eISSN: 1523-4681
DOI: 10.1002/jbmr.1997
Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4127979
Format
–
Schlagworte
Adult
,
Alleles
,
BDNF
,
BMD
,
Bone Density - genetics
,
Brain-Derived Neurotrophic Factor - metabolism
,
Cell Differentiation - genetics
,
Cell Line
,
Genotype
,
Humans
,
Middle Aged
,
OSTEOBLAST
,
Osteoblasts - cytology
,
Osteoblasts - enzymology
,
Phosphorylation - genetics
,
Polymorphism, Single Nucleotide - genetics
,
PROTEIN PHOSPHORYLATION
,
Reproducibility of Results
,
SNP
,
Substrate Specificity
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