Influence of estrogen receptor α polymorphisms on bone density in response to habitual exercise in Japanese postmenopausal women.
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ABSTRACT:
SUBMITTER: Kondo H
PROVIDER: S-EPMC4134819 | biostudies-other | 2014
REPOSITORIES: biostudies-other
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Project description:Adiponectin may affect bone through interactions with two known receptors, adiponectin receptors (ADIPOR) 1 and 2. We examined the association between polymorphisms of ADIPOR1 and ADIPOR2 and bone mineral density (BMD) in postmenopausal Korean women. Six polymorphisms in ADIPOR1 and four polymorphisms in ADIPOR2 were selected and genotyped in all study participants (n = 1,329). BMD at the lumbar spine and femur neck were measured using dual-energy X-ray absorptiometry. Lateral thoracolumbar (T4-L4) radiographs were obtained for vertebral fracture assessment and the occurrence of non-vertebral fractures examined using self-reported data. P values were adjusted for multiple testing using Bonferroni correction (P(corr)). ADIPOR1 rs16850799 and rs34010966 polymorphisms were significantly associated with femur neck BMD (P(corr) = 0.036 in the dominant model; P(corr) = 0.024 and P(corr) = 0.006 in the additive and dominant models, respectively). Subjects with the rare allele of each polymorphism had lower BMD, and association of rs34010966 with BMD showed a gene dosage effect. However, ADIPOR2 single nucleotide polymorphisms and haplotypes were not associated with BMD at any site. Our results suggest that ADIPOR1 polymorphisms present a useful genetic marker for BMD in postmenopausal Korean women.
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Project description:ObjectivePredictions of the future bone mineral density and bone loss rate are important to tailor medicine for women with osteoporosis, because of the possible presence of personal risk factors affecting the severity of osteoporosis in the future. We investigated whether it was possible to predict bone mineral density and bone loss rate in the future using artificial neural networks.ResultsA total of 135 women over 50 years old residing in T town of Wakayama Prefecture, Japan were analyzed to establish a statistical model. Artificial neural networks models were constructed using the two variables of bone mineral density and bone loss rate. The multiple correlation coefficients between the actual and measured values for lumbar and femoral bone mineral densities in 2003 showed R2 = 0.929 and R2 = 0.880, respectively, by linear regression analyses, while the values for bone loss rates in lumbar and femoral bone mineral densities were R2 = 0.694 and R2 = 0.609, respectively. Statistical models by artificial neural networks were superior to those by multiple regression analyses. The prediction of future bone mineral density values estimated by artificial neural networks was considered to be useful as a tool to tailor medicine for the early diagnosis of and intervention for women osteoporosis with women.
| S-EPMC5681768 | biostudies-literature
Project description:BackgroundOxidative stress has been recently suggested to play a part in the development of osteoporosis. Catalase is a major antioxidant enzyme that detoxifies hydrogen peroxide by converting it into water and oxygen, thereby preventing cellular injury by oxidative stress.AimsTo examine the associations between the catalase gene (CAT) polymorphisms and bone mineral density (BMD) and bone turnover markers in postmenopausal Korean women.MethodsAll exons, their boundaries and the promoter region (approximately 1.5 kb) were directly sequenced in 24 individuals. Among 18 variants identified by a direct sequence method, four polymorphisms were selected and genotyped in all study participants (n = 560). BMD at the lumbar spine and proximal femur was measured using dual-energy x ray absorptiometry. Serum osteocalcin concentrations and bone-specific alkaline phosphatase activity were determined by an immunoradiometric assay and an immunoassay, respectively.ResultsThe mean (standard deviation) age of the participants was 59.4 (7.2) years. Multivariate analysis showed an association of the +22348C-->T polymorphism with BMD at the lumbar spine (p = 0.01 in the dominant model) and at femur neck (p = 0.05 in the dominant model), and with serum osteocalcin level (p = 0.008 in the dominant model). Haplotype analyses showed that HT4 (-20T, +144C, +22348T, +33078A) was significantly associated with higher BMD at various sites (p<0.001-0.03) and with lower serum osteocalcin levels (p = 0.01 in the codominant model).ConclusionsThese findings indicate that the +22348C-->T polymorphism and HT4 of CAT may be useful genetic markers for bone metabolism.
| S-EPMC2597917 | biostudies-literature
Project description:BackgroundThe study investigated the associations of rs9340799:A > G (XbaI) and rs2234693:T > C (PvuII) polymorphisms in the estrogen receptor 1 gene (ESR1) with femoral neck (BMD-FN) and lumbar spine bone mineral density (BMD-LS), biochemical markers of bone turnover, calcium and phosphate levels, fracture prevalence, and a response to two types of anti-osteoporotic therapy in postmenopausal women from southern Slovakia.MethodsWe analysed 343 postmenopausal Slovak women (62.40 ± 0.46 years). The influence of rs9340799 (AA vs. AG + GG) and rs2234693 (TT vs. TC + CC) genotypes on BMD and biochemical markers was evaluated by covariance analysis adjusted for age and BMI. Binary logistic regression was used to evaluate the genotype effect on fracture prevalence. Pharmacogenetic part of the study included women who received a regular therapy of HT (17ß estradiol with progesterone; 1 mg/day for both; N = 76) or SERMs/raloxifene (60 mg/day; N = 64) during 48 months. The genotype-based BMD change was assessed by variance analysis for repeated measurements.ResultsWomen with AA genotype of rs9340799 had higher BMD-FN (+ 0.12 ± 0.57 of T-score) and BMD-LS (+ 0.17 ± 0.08 of T-score) in comparison with AG + GG. The rs2234693 polymorphism did not affect any of the monitored parameters. No effect of any ESR1 polymorphisms was found on fracture prevalence. Both types of anti-osteoporotic therapy had a positive effect on BMD improvement in FN and LS sites. Considering the effect of the ESR1 gene within the HT, the subjects with rs9340799/AA genotype showed worse response than those with GG genotype (- 0.26 ± 0.10 of BMD-FN T-score; - 0.35 ± 0.10 of BMD-LS T-score) and also with AG genotype (- 0.22 ± 0.08 of BMD-LS T-score). The rs2234693/TT genotype responded poorer in BMD-LS in comparison with TC (- 0.22 ± 0.08 of T-score) and CC (- 0.35 ± 0.09 of T-score). The effect of the ESR1 gene on raloxifene therapy was reported only in BMD-LS. Subjects with rs9340799/AA genotype had a - 0.30 ± 0.11 of T-score worse response compared to AG genotype. The rs2234693/TT genotype showed - 0.39 ± 0.11 and - 0.46 ± 0.15 lower T-scores in comparison with TC and CC genotypes, respectively.ConclusionsThe rs9340799 polymorphism may contribute to decreased BMD in postmenopausal women from southern Slovakia; however, this is not related to higher fracture prevalence. Concurrently, both polymorphisms affected a response to analysed anti-osteoporotic therapies.
| S-EPMC6150952 | biostudies-literature
Project description:Osteoclasts are sole bone-resorbing cells and are formed by the fusion of osteoclast precursor cells (OCPs) derived from myeloid lineage cells. Animal studies reveal that circulating osteoclast precursor cells (cOCPs) in blood travel to bone and fuse with bone-resident osteoclasts. However, the characteristics of human cOCPs and their association with bone diseases remain elusive. We have identified and characterized human cOCPs and found a positive association between cOCPs and osteoporosis. Sorted cOCPs have a higher osteoclastogenic potential than other myeloid cells and effectively differentiate into osteoclasts. cOCPs exhibit distinct morphology and transcriptomic signatures. The frequency of cOCPs in the blood varies among treatment-naïve postmenopausal women and has an inverse correlation with lumbar spine bone density and a positive correlation with serum CTX, a bone resorption marker. The increased cOCPs in treatment-naïve osteoporosis patients were significantly diminished by denosumab, a widely used antiresorptive therapy. Our study reveals the distinctive identity of human cOCPs and the potential link between the dynamic regulation of cOCPs and osteoporosis and its treatment. Taken together, our study enhances our understanding of human cOCPs and highlights a potential opportunity to measure cOCPs through a simple blood test, which could potentially identify high-risk individuals.
2024-11-22 | GSE276973 | GEO
Project description:Osteoclasts are sole bone-resorbing cells and are formed by the fusion of osteoclast precursor cells (OCPs) derived from myeloid lineage cells. Animal studies reveal that circulating osteoclast precursor cells (cOCPs) in blood travel to bone and fuse with boneresident osteoclasts. However, the characteristics of human cOCPs and their association with bone diseases remain elusive. We have identified and characterized human cOCPs and found a positive association between cOCPs and osteoporosis. Sorted cOCPs have a higher osteoclastogenic potential than other myeloid cells and effectively differentiate into osteoclasts. cOCPs exhibit distinct morphology and transcriptomic signatures. The frequency of cOCPs in the blood varies among treatment-naïve postmenopausal women and has an inverse correlation with lumbar spine bone density and a positive correlation with serum CTX, a bone resorption marker. The increased cOCPs in treatment-naïve osteoporosis patients were significantly diminished by denosumab, a widely used antiresorptive therapy. Our study reveals the distinctive identity of human cOCPs and the potential link between the dynamic regulation of cOCPs and osteoporosis and its treatment. Taken together, our study enhances our understanding of human cOCPs and highlights a potential opportunity to measure cOCPs through a simple blood test, which could potentially identify high-risk individuals.
2024-11-22 | GSE276768 | GEO
Project description:Introduction:Osteoporosis is a common age-related disease that is strongly influenced by genetics. Polymorphisms of the estrogen receptor gene alpha (ESR1) are consistently been associated with bone mineral density (BMD) and fracture.The purpose of this investigation was to evaluate potential association of single nucleotide polymorphism (SNP) variants of the ESR1 gene and bone mineral density (BMD) of the lumbar spine in Kazakh women. Methods:140 female participants in Pavlodar clinics with varying measures of BMD. We are examined the potential association of BMD with 2 SNPs from the ESR1 gene (rs2234693 [PvuII] and rs9340799 [XbaI]). Genotyping of the PvuII and XbaI polymorphisms was performed by direct sequencing of the gene fragments containing restriction sites with the identification of genotypes PP, Pp, pp and XX, Xx, xx respectively. Results:Unadjusted mean BMD values ranged from 1.14±0.14 g/cm2 in Caucasian women and 1.03±0.11 g/cm2 in Asian women. The association between PvuII polymorphism and BMD at the lumbar spine (p= 0.04 for PP=Pp=pp) was statistically significant in all women. The XbaI polymorphism was not associated with BMD at lumbar spine. The relative risk for low BMD was higher for the marker PvuII (RR=1.51) than for the marker XbaI (RR=1.35). Conclusion:The PvuII polymorphism had a weak association with lumbar spine BMD. XbaI polymorphism was unlikely to be a predictor of lumbar spine BMD in Kazakh women. These conclusions could help to determine the genetic risk factors for osteoporosis; however, further studies on the association between gene polymorphisms and BMD are needed including larger numbers of participants and genes to clarify genetic risks.
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Project description:Purpose Alendronate is a widely used anti-osteoporotic drug. PFN1 gene is a newly identified early-onset Paget’s disease pathogenic gene. The purpose of this study is to study whether the genetic variations in this gene affect the clinical efficacy of alendronate in postmenopausal Chinese women with low bone mass. Patients and Methods Seven single nucleotide polymorphisms in PFN1 gene were genotyped. A total of 500 postmenopausal women with osteoporosis or osteopenia were included. All participants were treated with weekly alendronate 70 mg for 12 months. A total of 466 subjects completed the follow-up. Bone mineral density (BMD) of lumbar spine, femoral neck and total hip were measured at baseline and after treatment. Results After 12 months of treatment, the BMD of lumbar spine, femoral neck and total hip all increased significantly (all P < 0.001), with an average increase of 4.72 ± 5.31%, 2.08 ± 4.45%, and 2.42 ± 3.46%, respectively. At baseline, there were no significant differences in BMD at lumbar spine, femoral neck and total hip between different genotype groups (P > 0.05). We failed to identify any significant association between the genotypes or haplotypes of PFN1 and the BMD response to alendronate therapy. Conclusion Genetic polymorphisms of PFN1 may not be a major contributor to the therapeutic response to alendronate treatment in Chinese women with low bone mass.
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Project description:AimA previous study shows that bone morphogenetic protein 7 (BMP7) gene polymorphisms are associated with bone mineral density (BMD) in 920 European Americans. To determine the association of BMP7 polymorphisms and BMD and osteoporotic fracture susceptibility, we performed a case-control association study in postmenopausal Chinese women with or without osteoporotic fracture.MethodsA total of 3815 unrelated postmenopausal Chinese women (1238 with osteoporotic fracture and 2577 healthy controls) were recruited. BMDs of the lumbar spine 1-4 (L1-4) and proximal femur (including total hip and femoral neck) were measured using dual-energy X-ray absorptiometry. Eight tagging single nucleotide polymorphisms (SNPs) in BMP7 gene, including rs11086598, rs4811822, rs12481628, rs6025447, rs230205, rs17404303, rs162316 and rs6127980, were genotyped.ResultsAmong the 8 SNPs, rs6025447 and rs230205 were associated with total hip BMD (P=0.013 and 0.045, respectively). However, the associations became statistically insignificant after adjusting for age, height and weight. The TGTG haplotype of BMP7 gene was associated with total hip BMD (P=0.032), even after adjusting for age, height and weight (P=0.048); but the association was insignificant after performing the Bonferroni multiple-significance-test correction. Moreover, the 8 SNPs and 9 haplotypes of BMP7 gene were not associated with L1-4 or femoral neck BMD or osteoporotic fracture.ConclusionThis large-sample case-control association study suggests that the common genetic polymorphisms of BMP7 gene are not major contributors to variations in BMD or osteoporotic fracture in postmenopausal Chinese women.
| S-EPMC4973379 | biostudies-literature
Project description:Background: The relationship between bone metabolism-related gene polymorphisms and low bone mineral density (BMD) risk factors in female athletes is unclear. This study aimed at investigating whether the sensitivity of low BMD risk factors to BMD depends on estrogen receptor α (ERα) gene polymorphisms in Japanese female athletes. Materials and Methods: This study included 280 collegiate female athletes from 12 competitive sports (age, 19.2 ± 1.3 years). Data on sports participation, age at menarche, menstrual cycles, prior stress fractures, and prior eating disorders were obtained through a questionnaire-type survey. Sports types were classified into endurance, esthetic, aquatic, ball, and high load in consideration of exercise load characteristics. ERα gene PvuII (rs2234693) and XbaI (rs9340799) polymorphisms were analyzed by TaqMan® assay. The total body BMD was measured by dual-energy X-ray absorptiometry. Results: On multiple regression analysis, sports types, body mass index (BMI), menarche, and XbaI polymorphism remained robust independent predictors of BMD. However, prior stress fractures and menstrual cycles were excluded. In athletes carrying the XX+Xx genotype of XbaI polymorphism, sports types and BMI were associated with BMD. However, in athletes carrying the xx genotype of XbaI polymorphism, sports types, BMI, and menarche were associated with BMD. These results indicated that athletes carrying the xx genotype with delayed menarche had low BMD. Conclusions: In collegiate female athletes, participation in endurance, esthetic, and aquatic sports types and a low BMI are associated with low BMD. In addition, delayed menarche may negatively affect BMD in athletes carrying the xx type of ERα gene XbaI polymorphism.
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