Dataset Information

Common variants in FLNB/CRTAP, not ARHGEF3 at 3p, are associated with osteoporosis in southern Chinese women.

ABSTRACT: SUMMARY: We performed an association study of five candidate genes within chromosome 3p14-25 in 1,080 Chinese female subjects. Polymorphisms in FLNB/CRTAP are associated with bone mineral density (BMD) in Chinese. INTRODUCTION: Chromosomal region 3p14-25 has shown strong evidence of linkage to BMD in genome-wide linkage scans. The variants responsible for this linkage signal, nonetheless, remain obscure. METHODS: Thirty SNPs in five positional and functional candidate genes within 3p14-25 (PPARG, CRTAP, TDGF1, PTHR1, and FLNB) and rs7646054 in the ARHGEF3 gene were genotyped in a case-control cohort of 1,080 Chinese females. Allelic and haplotypic association were tested using logistic regression analysis implemented in PLINK software. Potential transcription factor binding sites were predicted with MatInspector. RESULTS: Multiple SNPs and haplotypes in FLNB were significantly associated with BMDs, with the strongest association between lumbar spine BMD and rs9828717 (p = 0.005). SNP rs7623768 and the haplotype G-C of rs4076086-rs7623768 in CRTAP were associated with femoral neck BMD (p = 0.009 and p = 0.003, respectively). PTHR1 showed haplotypic associations with lumbar spine and femoral neck BMD (p = 0.02 and p = 0.044, respectively). Nevertheless, the association between rs7646054 in ARHGEF3 and BMD observed in Caucasians was not replicated in our samples. Comparative genomics analysis indicated that rs9828717 is located within a highly conserved region. The minor T allele at rs9828717 may lead to loss of binding site for nuclear factor of activated T cells which binds and triggers the transcriptional program of osteoblasts. CONCLUSIONS: Our data suggest that variants in FLNB and CRTAP at 3p are involved in BMD regulation in southern Chinese.

SUBMITTER: Li GH

PROVIDER: S-EPMC2946578 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature

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Common variants in FLNB/CRTAP, not ARHGEF3 at 3p, are associated with osteoporosis in southern Chinese women.

Li G H Y GH Kung A W C AW Huang Q-Y QY

Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 20090901 6

<h4>Summary</h4>We performed an association study of five candidate genes within chromosome 3p14-25 in 1,080 Chinese female subjects. Polymorphisms in FLNB/CRTAP are associated with bone mineral density (BMD) in Chinese.<h4>Introduction</h4>Chromosomal region 3p14-25 has shown strong evidence of linkage to BMD in genome-wide linkage scans. The variants responsible for this linkage signal, nonetheless, remain obscure.<h4>Methods</h4>Thirty SNPs in five positional and functional candidate genes wi ...[more]

PMID: 19727905

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Project description:BackgroundObesity is associated with improved bone mass and microarchitecture in Caucasian individuals, but evidence in obese Asian individuals is lacking.ObjectiveTo analyze the areal bone mineral density (aBMD) and bone microarchitecture in normal-weight, overweight, and obese postmenopausal Chinese women.MethodsA total of 243 postmenopausal women from the Chinese Vertebral Osteoporosis Study (ChiVOS) were included and were divided into three groups (OB, obese group; OW, overweight group; NW, normal weight group) by BMI level. aBMD, trabecular bone score (TBS), and appendicular lean mass (ALM) were measured by dual-energy X-ray absorptiometry (DXA). Bone microarchitecture was measured by HR-pQCT at the distal radius and tibia. X-ray was performed to confirm vertebral fractures (VFs). Multiple linear regression was used to evaluate the correlations between bone parameters and ALM after adjusting for confounding variables.ResultsThe prevalence of VFs and clinical fractures were similar among the groups. Participants in the OB group showed a lower level of osteocalcin with comparable levels of other bone turnover markers (BTMs). The aBMD at several skeletal sites was higher in the OB group than in the NW group after adjusting for age (p<0.01 for all comparisons). At the radius, the OB group had a higher Ct.Ar, Tb.vBMD, Tb.BV/TV, Tb.N, Tb.Th, and Ct.Th than the NW group after adjusting for covariates (p<0.05 for all). Differences of a similar magnitude were found at the distal tibia. There was a trend of decreasing trend in Tb.Sp, Tb.1/N/SD, and Ct.Po among groups at both sites. However, the bone microarchitecture did not differ between participants with severe obesity (BMI≥35.0kg/m2) and those with 30.0≤BMI<35 kg/m2. Multiple linear regression revealed that the associations between ALM and most of the bone microarchitecture parameters at both sites were much stronger than the association between body weight and bone parameters.ConclusionWe have observed significant improvements in aBMD, bone geometry, and bone microarchitecture in obese postmenopausal Chinese women. Except for a lower level of osteocalcin in the OB group, no significant differences in BTMs were found among the groups. Compared with body weight, ALM may explain greater variance in the improvement of bone microarchitecture parameters.

Dataset Information

Common variants in FLNB/CRTAP, not ARHGEF3 at 3p, are associated with osteoporosis in southern Chinese women.

Publications

Common variants in FLNB/CRTAP, not ARHGEF3 at 3p, are associated with osteoporosis in southern Chinese women.

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