PMID- 28903900
OWN - NLM
STAT- MEDLINE
DCOM- 20171205
LR  - 20180816
IS  - 0253-9772 (Print)
IS  - 0253-9772 (Linking)
VI  - 39
IP  - 8
DP  - 2017 Aug 20
TI  - Genetics association study and functional analysis on osteoporosis susceptibility 
      gene BDNF.
PG  - 726-736
LID - 10.16288/j.yczz.17-145 [doi]
AB  - To explore the relationship between brain-derived neurotrophic factor (BDNF) gene 
      and bone mineral density (BMD) in Chinese Han population, we performed 
      association analysis of 14 tag SNPs on BDNF gene with hip/spine BMD in 1300 Han 
      Chinese samples from Shaanxi Province. We found that 8 of the 14 SNPs were 
      significantly associated with hip or spine BMD (P < 0.05). Moreover, the SNP 
      rs16917237 was significantly associated with both hip and spine BMD, with 
      significant Bonferroni correlation (P value 0.05/14 = 0.0036) in hip BMD. To 
      further explore the regulatory mechanism of BDNF gene in osteoporosis, we further 
      performed a set of data analyses, including linkage disequilibrium and haplotype 
      analysis, epigenetic annotation, expression quantitative trait locus (eQTL) 
      analysis and metabolic pathway analysis. Further, we have established a mouse 
      pre-osteoblasts differentiation cell model (MC3T3-E1) by recombination human bone 
      morphogenetic protein (rh-BMP2) induction. siRNA- mediated knock down of BDNF in 
      this cell model showed that all 14 SNPs are in the same haplotype block. Strong 
      signals of active histone H3K4me1, H3K4me3, H3K27ac modifications and P300 
      binding were observed in osteoblasts, in the region surrounding the most 
      significant SNP rs16917237, suggesting that this SNP might have a regulatory 
      function in osteoblasts. Furthermore, analysis of genotype data of rs16917237 and 
      BDNF expression in multiple tissues from GTEx showed that rs16917237 SNP could 
      significantly affect the expression of BDNF in 11 tissues. Through analysis of 
      the various BDNF pathways, we showed that BDNF participates in the MAPK pathway, 
      which is a vital and well-established pathway affecting osteoblasts proliferation 
      and differentiation. siRNA knock down of BDNF significantly decreased the mRNA 
      and protein levels of CREB, which is important in the MAPK pathway in osteoblast 
      differentiation. These findings suggest that BDNF might affect osteoblast 
      differentiation via regulation of CREB expression. In conclusion, our results 
      from combined genetic association and functional analyses show that BDNF is a 
      vital osteoporosis susceptibility gene, which can affect BMD not only in Chinese 
      Han but also likely in other populations.
FAU - Yang, Man
AU  - Yang M
AD  - Key Laboratory of Biomedical Information Engineering of Ministry of Education, 
      and Institute of Molecular Genetics, School of Life Science and Technology, Xi'an 
      Jiaotong University, Xi'an 710049, China.
FAU - Lu, Bing-Jie
AU  - Lu BJ
AD  - Key Laboratory of Biomedical Information Engineering of Ministry of Education, 
      and Institute of Molecular Genetics, School of Life Science and Technology, Xi'an 
      Jiaotong University, Xi'an 710049, China.
FAU - Duan, Yuan-Yuan
AU  - Duan YY
AD  - Key Laboratory of Biomedical Information Engineering of Ministry of Education, 
      and Institute of Molecular Genetics, School of Life Science and Technology, Xi'an 
      Jiaotong University, Xi'an 710049, China.
FAU - Chen, Xiao-Feng
AU  - Chen XF
AD  - Key Laboratory of Biomedical Information Engineering of Ministry of Education, 
      and Institute of Molecular Genetics, School of Life Science and Technology, Xi'an 
      Jiaotong University, Xi'an 710049, China.
FAU - Ma, Jian-Gang
AU  - Ma JG
AD  - Key Laboratory of Biomedical Information Engineering of Ministry of Education, 
      and Institute of Molecular Genetics, School of Life Science and Technology, Xi'an 
      Jiaotong University, Xi'an 710049, China.
FAU - Guo, Yan
AU  - Guo Y
AD  - Key Laboratory of Biomedical Information Engineering of Ministry of Education, 
      and Institute of Molecular Genetics, School of Life Science and Technology, Xi'an 
      Jiaotong University, Xi'an 710049, China.
LA  - eng
PT  - Journal Article
PL  - China
TA  - Yi Chuan
JT  - Yi chuan = Hereditas
JID - 9436478
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 7171WSG8A2 (BDNF protein, human)
SB  - IM
MH  - Adult
MH  - Brain-Derived Neurotrophic Factor/*genetics
MH  - Female
MH  - Genetic Predisposition to Disease/*genetics
MH  - Genotype
MH  - Humans
MH  - Male
MH  - Osteoporosis/*genetics
MH  - Polymorphism, Single Nucleotide/*genetics
EDAT- 2017/09/15 06:00
MHDA- 2017/12/06 06:00
CRDT- 2017/09/15 06:00
PHST- 2017/09/15 06:00 [entrez]
PHST- 2017/09/15 06:00 [pubmed]
PHST- 2017/12/06 06:00 [medline]
AID - 10.16288/j.yczz.17-145 [doi]
PST - ppublish
SO  - Yi Chuan. 2017 Aug 20;39(8):726-736. doi: 10.16288/j.yczz.17-145.