Objective To investigate the effects of the genetic polymorphisms in osteoporosis-related genes and the gene-gene interaction on bone mineral density (BMD) and osteoporotic fractures.Methods Thirty-nine single nucleotide polymorphism (SNP) sites in 23 genes that related to bone mineral density ( BMD ) and osteoporotic fractures were scanned in 683 Shanghai Han postmenopausal women.TaqMan SNP Genotyping Assay or Sequenom Mass ARRAY System were applied for genotyping analysis.The relation of these SNP sites with BMD and osteoporotic fractures were analyzed.Results Altogether,12 SNPs in 9 candidate genes ( rs7524102 and rs6696981 in ZBTB40 gene,rs9479055 in ESR1 gene,rs6993813,rs6469804,and rs11995824 in OPG gene,rs3736228 in LRP5 gene,rs1107748 in SOST gene,rs87938 in CTNNB1 gene,rs1366594 in MEF2C gene,rs7117858 in SOX6 gene,and rs10048146 in FOXL1 gene) were associated with BMD at lumbar spine(L1-L4) or total hip.In addition,rs11898505 in SPTBN1 gene was related to osteoporotic fractures ( OR 0.522,95％ CI 0.326-0.838,P =0.007 ).Gene-gene interaction involving rs1038304 in ESR1 gene,rs1366594 in MEF2C gene,and rs10048146 in FOXL1 gene was associated with osteoporotic fractures ( P =0.010 7 ).Conclusions ( 1 ) SNPs in gene ZBTB40,ESR1,OPG,LRP5,SOST,CTNNB1,MEF2C,SOX6,FOXL1,and SPTBN1 are associated with BMD of lumbar spine or total hip,as well as osteoporotic fractures.(2) Gene-gene interaction involving rs1038304,rs1366594,and rs10048146may contribute to the risk of osteoporotic fractures.

【Objective】 To study the effect of metformin (Met) hydrochloride on the expressions of inflammatory cytokines in Aβ1-42-induced BV-2 cells and its mechanisms. 【Methods】 BV-2 cells were induced by Aβ1-42 to mimic the neuroinflammatory cell model, and after treatment with Met, the contents of cytokines, including TNF-α, IL-1β, IL-6 and IL-18, in cell supernatant were examined by ELISA; the mRNA levels of TNF-α, IL-1β, IL-6 and IL-18 were examined by RT-PCR; and the expressions of NLRP3, ASC, pro-Caspase-1, Caspase-1, NF-κB, p-IκBα and IκBα were examined by Western blotting. 【Results】 Aβ1-42 at 1.25, 2.5 and 5 μmol/L could decrease the BV-2 cell viability in a dose-dependent manner, while Met at 0.5, 1 and 2 mmol/L could increase the cell viability in 5 μmol/L Aβ1-42-induced BV-2 cells. After treatment with Met, the transcription and secretion of TNF-α, IL-1β, IL-6 and IL-18, and the protein expressions of NLRP3, ASC, Caspase-1(p20), NF-κB and p-IκBα were significantly decreased in Aβ1-42-induced BV-2 cells. 【Conclusion】 Met attenuates inflammatory responses in Aβ1-42-induced BV-2 cells, which may be associated with the inhibition of NLRP3 inflammasome activation via NF-κB pathway.