The region rs1718454–rs9822918 was significantly associated with total hip BMD (p = 0.027). The C–T and T–G haplotype were correspondingly associated LDK378 concentration with the increased (p = 0.006, OR = 1.69) and reduced risk of low BMD (p = 0.025, OR = 0.66). The global omnibus test demonstrated that the region rs4076086–rs7623768 in CRTAP was significantly

associated with femoral neck (p = 0.028) and total hip BMD (p = 0.015). According to the haplotype-specific and conditional haplotype test, G–C was potentially the haplotype that conferred a protective effect on femoral neck (p = 0.003, OR = 0.43) and total hip (p = 0.007, OR = 0.44) BMD. rs7646054 in ARHGEF3 and BMD Mullin et al. [14] recently reported a significant association between rs7646054 and BMD Z-score in postmenopausal women: subjects homozygous for the G allele had lower BMD than subjects heterozygous or homozygous for the A allele. The same model (AA + AG vs GG) was, therefore, adopted in the analysis of this SNP using logistic regression implemented in SPSS. No Selumetinib association was observed between rs7646054 and BMD Z-score at the lumbar spine, femoral neck, or total hip in the whole study population,

nor in the 533 postmenopausal case-controls (results not shown). Bioinformatics analysis Since four of the five SNPs genotyped within intron 1 of FLNB showed significant associations with BMD in the single-marker test, the chromosomal position of intron 1 (Chr3:57,969,624-58,037,812) was submitted to VISTA genome browser to determine the presence of any potential conserved elements. RankVISTA for multiple alignment shows that intron 1 of FLNB in humans is a conserved noncoding sequence among five other species, including rhesus, dog, horse, mouse, and rat (Fig. 1). It is worth

noting that rs9828717 is located within a highly conserved region with an alignment p value of 2.4 × 10−16. Prediction of potential transcription factor binding sites with MatInspector revealed that the minor T allele at rs9828717 may lead to the loss of binding site for nuclear factor of activated T cells (NFAT). The similarity score for the major C allele with NFAT matrix was 0.96. Fig. 1 VISTA browser plot of the comparative selleck chemicals analysis for intron 1 in FLNB (Chr3:57,969,624-58,037,812 on the human March 2006 genome). The position of rs9828717 was indicated by the red arrow Discussion In the present study, we tested associations between common variants in five candidate genes in 3p14-25 (FLNB, PPARG, TDGF1, CRTAP, and PTHR1) and BMD in 1,080 southern Chinese women. Among these candidate genes, FLNB showed the strongest and most consistent association with BMD in both single-marker and haplotype analysis. At the SNP level, rs9828717, rs1718456, rs1718454, and rs9822918 were significantly associated with lumbar spine, femoral neck, or total hip BMD (p = 0.005–0.029).