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The ESR1 (6q25) locus is associated with calcaneal ultrasound parameters and radial volumetric bone mineral density in European men.

ABSTRACT: Genome-wide association studies (GWAS) have identified 6q25, which incorporates the oestrogen receptor ? gene (ESR1), as a quantitative trait locus for areal bone mineral density (BMD(a)) of the hip and lumbar spine. The aim of this study was to determine the influence of this locus on other bone health outcomes; calcaneal ultrasound (QUS) parameters, radial peripheral quantitative computed tomography (pQCT) parameters and markers of bone turnover in a population sample of European men.Eight single nucleotide polymorphisms (SNP) in the 6q25 locus were genotyped in men aged 40-79 years from 7 European countries, participating in the European Male Ageing Study (EMAS). The associations between SNPs and measured bone parameters were tested under an additive genetic model adjusting for centre using linear regression.2468 men, mean (SD) aged 59.9 (11.1) years had QUS measurements performed and bone turnover marker levels measured. A subset of 628 men had DXA and pQCT measurements. Multiple independent SNPs showed significant associations with BMD using all three measurement techniques. Most notably, rs1999805 was associated with a 0.10 SD (95%CI 0.05, 0.16; p?=?0.0001) lower estimated BMD at the calcaneus, a 0.14 SD (95%CI 0.05, 0.24; p?=?0.004) lower total hip BMD(a), a 0.12 SD (95%CI 0.02, 0.23; p?=?0.026) lower lumbar spine BMD(a) and a 0.18 SD (95%CI 0.06, 0.29; p?=?0.003) lower trabecular BMD at the distal radius for each copy of the minor allele. There was no association with serum levels of bone turnover markers and a single SNP which was associated with cortical density was also associated with cortical BMC and thickness.Our data replicate previous associations found between SNPs in the 6q25 locus and BMD(a) at the hip and extend these data to include associations with calcaneal ultrasound parameters and radial volumetric BMD.

SUBMITTER: Holliday KL

PROVIDER: S-EPMC3131390 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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The ESR1 (6q25) locus is associated with calcaneal ultrasound parameters and radial volumetric bone mineral density in European men.

Holliday Kate L KL Pye Stephen R SR Thomson Wendy W Boonen Steven S Borghs Herman H Vanderschueren Dirk D Gielen Evelien E Huhtaniemi Ilpo T IT Adams Judith E JE Ward Kate A KA Bartfai Gyorgy G Casanueva Felipe F Finn Joseph D JD Forti Gianni G Giwercman Aleksander A Han Thang S TS Kula Krzysztof K Labrie Fernand F Lean Michael E J ME Pendleton Neil N Punab Margus M Wu Frederick C W FC O'Neill Terence W TW

PloS one 20110707 7

<h4>Purpose</h4>Genome-wide association studies (GWAS) have identified 6q25, which incorporates the oestrogen receptor α gene (ESR1), as a quantitative trait locus for areal bone mineral density (BMD(a)) of the hip and lumbar spine. The aim of this study was to determine the influence of this locus on other bone health outcomes; calcaneal ultrasound (QUS) parameters, radial peripheral quantitative computed tomography (pQCT) parameters and markers of bone turnover in a population sample of Europe ...[more]

PMID: 21760950

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Project description:BackgroundCalcaneal quantitative ultrasound (QUS), which is used in the evaluation of osteoporosis, is believed to be intimately associated with the characteristics of the proximal femur. However, the specific associations of calcaneal QUS with characteristics of the hip sub-regions remain unclear.DesignA cross-sectional assessment of 53 osteoporotic patients was performed for the skeletal status of the heel and hip.MethodsWe prospectively enrolled 53 female osteoporotic patients with femoral fractures. Calcaneal QUS, dual energy X-ray absorptiometry (DXA), and hip structural analysis (HSA) were performed for each patient. Femoral heads were obtained during the surgery, and principal compressive trabeculae (PCT) were extracted by a three-dimensional printing technique-assisted method. Pearson's correlation between QUS measurement with DXA, HSA-derived parameters and Young's modulus were calculated in order to evaluate the specific association of QUS with the parameters for the hip sub-regions, including the femoral neck, trochanteric and Ward's areas, and the femoral shaft, respectively.ResultsSignificant correlations were found between estimated BMD (Est.BMD) and BMD of different sub-regions of proximal femur. However, the correlation coefficient of trochanteric area (r = 0.356, p = 0.009) was higher than that of the neck area (r = 0.297, p = 0.031) and total proximal femur (r = 0.291, p = 0.034). Furthermore, the quantitative ultrasound index (QUI) was significantly correlated with the HSA-derived parameters of the trochanteric area (r value: 0.315-0.356, all p<0.05) as well as with the Young's modulus of PCT from the femoral head (r = 0.589, p<0.001).ConclusionThe calcaneal bone had an intimate association with the trochanteric cancellous bone. To a certain extent, the parameters of the calcaneal QUS can reflect the characteristics of the trochanteric area of the proximal hip, although not specifically reflective of those of the femoral neck or shaft.

Project description:Osteoporosis has been linked with increased risk of cardiovascular disease previously. However, few studies have detailed bone and vascular information. In a prospective study of older women, we demonstrated heel quantitative ultrasound measures were associated with increased cardiovascular and all-cause mortality, independent of established cardiovascular risk factors.IntroductionOsteoporosis and low bone mineral density (BMD) have been previously linked to cardiovascular disease (CVD) and mortality. Calcaneal quantitative ultrasound (QUS) is used to evaluate bone material properties, especially in older women. However, it is uncertain whether it is related to risk of mortality. This study was aimed to investigate the association between calcaneal QUS measurements and 15-year all-cause and CVD mortality in 1404 older women (mean age 75.2 ± 2.7 years).MethodsOne thousand four hundred four older women, participants of Calcium Intake Fracture Outcome study (CAIFOS), had calcaneal bone measured at baseline (1998) and followed for 15 years. The primary outcomes, any deaths, and deaths attributable to cardiovascular causes ascertained by using linked data were obtained from Western Australia data linkage system.ResultsOver the 15 years of follow-up (17,955 person years), 584 of the women died, and 223 from CVD. For every standard deviation (SD), reduction in broadband ultrasound attenuation (BUA) in minimally and multivariable-adjusted model including cardiovascular risk factors increased relative hazards for all-cause (multivariable-adjusted HR 1.15; 95%CI: 1.06-1.26, p = 0.001) and CVD mortality (multivariable-adjusted HR 1.20; 95%CI: 1.04-1.38, p = 0.010). Such relationships also persisted when hip BMD was included in the model (all-cause mortality HR 1.19; 95%CI: 1.07-1.33, p = 0.002; CVD mortality HR 1.28; 95%CI: 1.07-1.53, p = 0.008).ConclusionBUA is associated with all-cause and CVD mortality in older women independent of BMD and established CVD risk factors. Understanding why and how these are related may provide further insights about the bone-vascular nexus as well as therapeutic targets benefiting both systems.

Project description:Osteoporosis (OP) is a disease characterized by decreased bone mineral density (BMD) and an increased risk of osteoporotic fractures. Nutritional factors (including glucose and fats lipids), have been implicated in OP.We hypothesized that the levels of blood glucose and lipids could be biomarkers for predicting the risk of OP. To test this hypothesis, we evaluated the potential relationship between BMD and levels of blood glucose and lipids via a community-based study in China.This was a community-based cross-section analysis, and a total of 8584 cases were investigated. The BMD of the left calcaneus was measured using an ultrasonic bone densitometer. The levels of blood glucose (fasting blood glucose [FBG], 2-h blood glucose [2hBG], and glycosylated hemoglobin [HbAlc]), and lipids (triglyceride [TG], total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], and high-density lipoprotein cholesterol [HDL-C]) were measured and analyzed.In our study population, the levels of FBG, 2hBG, HbAlc, TC, LDL-C and HDL-C were higher in the OP group than in the low bone density and the normal bone density groups, while the levels of HbAlc, TC, and LDL-C in the low bone density group were higher than those in the normal bone density group. In males, the level of blood LDL-C in the low bone density group was higher than that in the normal bone density group. In postmenopausal subjects, the levels of FBG, 2hBG and HbA1C were higher than those in the normal bone density groups, and the level of HbA1C in the low bone density group was higher than that in the normal bone density group. Pearson linear trend analysis demonstrated that BMD was positively associated with TC and LDL-C in males and negatively associated with FBG, 2hBG and HbA1C in postmenopausal females. Moreover, logistic analysis showed that BMD was correlated with TC in premenopausal females and HbA1C in postmenopausal females.OP is generally associated with abnormal levels of blood glucose and/or lipids; nevertheless, the relationship between OP and abnormal levels of blood glucose and/or lipids is complicate and different subpopulations may have different susceptibilities. Therefore, further detailed studies are warranted.

Project description:BackgroundPeripheral pulmonary lesion (PPL) incidence is rising because of increased chest imaging sensitivity and frequency. For PPLs suspicious for lung cancer, current clinical guidelines recommend tissue diagnosis. Radial endobronchial ultrasound (R-EBUS) is a bronchoscopic technique used for this purpose. It has been observed that diagnostic yield is impacted by the ability to accurately manipulate the radial probe. However, such skills can be acquired, in part, from simulation training. Three-dimensional (3D) printing has been used to produce training simulators for standard bronchoscopy but has not been specifically used to develop similar tools for R-EBUS.ObjectiveWe report the development of a novel ultrasound-compatible, anatomically accurate 3D-printed R-EBUS simulator and evaluation of its utility as a training tool.MethodsComputed tomography images were used to develop 3D-printed airway models with ultrasound-compatible PPLs of "low" and "high" technical difficulty. Twenty-one participants were allocated to two groups matched for prior R-EBUS experience. The intervention group received 15 minutes to pretrain R-EBUS using a 3D-printed model, whereas the nonintervention group did not. Both groups then performed R-EBUS on 3D-printed models and were evaluated using a specifically developed assessment tool.ResultsFor the "low-difficulty" model, the intervention group achieved a higher score (21.5 ± 2.02) than the nonintervention group (17.1 ± 5.7), reflecting 26% improvement in performance (P = 0.03). For the "high-difficulty" model, the intervention group scored 20.2 ± 4.21 versus 13.3 ± 7.36, corresponding to 52% improvement in performance (P = 0.02). Participants derived benefit from pretraining with the 3D-printed model, regardless of prior experience level.Conclusion3D-printing can be used to develop simulators for R-EBUS education. Training using these models significantly improves procedural performance and is effective in both novice and experienced trainees.

Project description:BackgroundBreast cancer is a partially heritable trait and genome-wide association studies (GWAS) have identified over 180 common genetic variants associated with breast cancer. We have previously performed breast cancer GWAS in Latinas and identified a strongly protective single nucleotide polymorphism (SNP) at 6q25, with the protective minor allele originating from indigenous American ancestry. Here we report on fine mapping of the 6q25 locus in an expanded sample of Latinas.MethodsWe performed GWAS in 2385 cases and 6416 controls who were either US Latinas or Mexican women. We replicated the top SNPs in 2412 cases and 1620 controls of US Latina, Mexican, and Colombian women. In addition, we validated the top novel variants in studies of African, Asian and European ancestry. In each dataset we used logistic regression models to test the association between SNPs and breast cancer risk and corrected for genetic ancestry using either principal components or genetic ancestry inferred from ancestry informative markers using a model-based approach.ResultsWe identified a novel set of SNPs at the 6q25 locus associated with genome-wide levels of significance (p = 3.3 × 10- 8 - 6.0 × 10- 9) not in linkage disequilibrium (LD) with variants previously reported at this locus. These SNPs were in high LD (r2 > 0.9) with each other, with the top SNP, rs3778609, associated with breast cancer with an odds ratio (OR) and 95% confidence interval (95% CI) of 0.76 (0.70-0.84). In a replication in women of Latin American origin, we also observed a consistent effect (OR 0.88; 95% CI 0.78-0.99; p = 0.037). We also performed a meta-analysis of these SNPs in East Asians, African ancestry and European ancestry populations and also observed a consistent effect (rs3778609, OR 0.95; 95% CI 0.91-0.97; p = 0.0017).ConclusionOur study adds to evidence about the importance of the 6q25 locus for breast cancer susceptibility. Our finding also highlights the utility of performing additional searches for genetic variants for breast cancer in non-European populations.

Dataset Information

The ESR1 (6q25) locus is associated with calcaneal ultrasound parameters and radial volumetric bone mineral density in European men.

Publications

The ESR1 (6q25) locus is associated with calcaneal ultrasound parameters and radial volumetric bone mineral density in European men.

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