Dataset Information

Association of Adrenergic Receptor ?2A (?2A-AR) Gene rs1800544 Polymorphism with Bone Mineral Density and Bone Turnover Markers in an Elderly Chinese Population.

ABSTRACT: BACKGROUND Adrenergic receptor ?2A (?2A-AR) is up-regulated in osteoporotic bone osteoblasts. Previous research demonstrated an association between polymorphism of a2A-AR gene and bone mineral density (BMD) as well as bone turnover markers (BTMs) in the Slovenian population. The present study aimed to investigate the association of rs1800544 polymorphism of ?2A-AR gene with BMD and BTMs in the Chinese elderly population with osteoporosis (OP) or with osteoporotic fractures. MATERIAL AND METHODS A total of 346 unrelated elderly individuals were recruited in the study. Rs1800544 polymorphism was determined by Snapshot technology. BTMs were determined by electrochemiluminescence. BMDs at lumbar spine (LS) and proximal femur were measured with dual-energy X-ray absorptiometry (DEXA). Hardy-Weinberg equilibrium and distribution of genotype frequencies were verified using the chi-squared test. Analysis of co-variance (ANCOVA) adjusted for confounding factors was performed to explore the relationship of rs1800544 polymorphism with BMD and BTMs in all participants and in subgroups. RESULTS The genotype distributions in all subjects and in subgroups conformed to Hardy-Weinberg equilibrium (P>0.1). Distribution of genotype frequencies of subgroups showed no significant differences (P>0.05). Patients with GG genotype in the fracture group had significantly higher serum BTMs level compared with those carrying other genotypes (P<0.05). No significant association between rs1800544 and BTMs was detected in the elderly population with OP. Comparison of BMD at each site in all participants did not show any significant difference in subgroups with CC, CG, and GG genotypes (P>0.05). CONCLUSIONS Rs1800544 polymorphism is associated with BTMs level in Chinese elderly individuals with osteoporotic fractures, indicating the involvement of genetic variation of a2A-AR gene in bone metabolism.

SUBMITTER: Wang QF

PROVIDER: S-EPMC6067018 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Association of Adrenergic Receptor α2A (α2A-AR) Gene rs1800544 Polymorphism with Bone Mineral Density and Bone Turnover Markers in an Elderly Chinese Population.

Wang Qi-Fei QF Sun Zhe Z Zheng Fan-Rong FR Zhang Guang-Wu GW Liu Zheng Z

Medical science monitor : international medical journal of experimental and clinical research 20180723

BACKGROUND Adrenergic receptor α2A (α2A-AR) is up-regulated in osteoporotic bone osteoblasts. Previous research demonstrated an association between polymorphism of a2A-AR gene and bone mineral density (BMD) as well as bone turnover markers (BTMs) in the Slovenian population. The present study aimed to investigate the association of rs1800544 polymorphism of α2A-AR gene with BMD and BTMs in the Chinese elderly population with osteoporosis (OP) or with osteoporotic fractures. MATERIAL AND METHODS ...[more]

PMID: 30033441

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Project description:Purpose: The association between bone mineral density (BMD), bone turnover markers, and serum cholesterol in healthy population has already been proved. However, in patients with type 2 diabetes mellitus (T2D), it has not been adequately analyzed. In this study, we investigated the correlation between BMD, bone turnover markers, and serum cholesterol levels in people with T2D. Methods: We enrolled 1,040 men and 735 women with T2D from Zhongshan Hospital between October 2009 and January 2013. Their general condition, history of diseases and medication, serum markers, and BMD data were collected. We used logistic regression analysis to identify the association between serum cholesterol levels and BMD as well as bone turnover markers. Results: In multivariate regression analysis, we observed that in men with T2D, high high-density lipoprotein-cholesterol and total cholesterol levels were significantly associated with low total lumbar, femur neck, and total hip BMD, while low-density lipoprotein-cholesterol level was only inversely associated with total lumbar and femur neck BMD. Total cholesterol and low-density lipoprotein-cholesterol levels were also negatively associated with osteocalcin, procollagen type I N-terminal propeptide, and ?-crosslaps. In women with T2D, high-density lipoprotein-cholesterol level was observed to be negatively correlated with total lumbar, femur neck, and total hip BMD, while total cholesterol and low-density lipoprotein-cholesterol levels were only associated with BMD at the total lumbar. Furthermore, total cholesterol was also negatively associated with osteocalcin, procollagen type I N-terminal propeptide, and ?-crosslaps; high-density lipoprotein-cholesterol was only related to osteocalcin and parathyroid hormone, while low-density lipoprotein-cholesterol was only related to ?-crosslaps in women. Conclusion: Our study suggests a significantly negative correlation between serum cholesterol levels and BMD in both men and women with T2D. The associations between serum cholesterol levels and bone turnover markers were also observed in T2D patients.

Project description:IntroductionOsteoporosis (OP) is a common polygenic disorder in the aging population, and several single nucleotide polymorphisms (SNPs) in the alpha-L-iduronidase (IDUA) gene and patched homolog 1 (PTCH1) gene regulate bone metabolism and affect bone mass. The study aimed at investigating the relationships of rs3755955 and rs6831280 in the IDUA gene and rs28377268 in the PTCH1 gene with bone mineral density (BMD), bone turnover markers (BTMs), and fractures in the elderly Chinese subjects with OP.Materials and methodsA cohort of 328 unrelated senile osteoporosis (SOP) patients with or without osteoporotic fractures was recruited. rs3755955, rs6831280, and rs28377268 polymorphisms were identified using SNaPshot technology. BTM levels were determined by electrochemiluminescence (ECL). Bone mineral densities (BMDs) at the lumbar spine (LS) and proximal femur sites were measured by dual-energy X-ray absorptiometry (DEXA) in all subjects. The Hardy-Weinberg equilibrium (HWE) test was performed. HWE P values and comparisons of genotype frequencies were estimated using the chi-square test. Analysis of covariance (ANCOVA) adjusted for confounding factors was performed to investigate associations of SNPs with BMDs and BTMs in subgroups.ResultsThe chi-square test indicated that genotype distributions in the control group conformed to HWE (P > 0.05). The distributions of allele and genotype frequencies of rs6831280 between fracture and osteoporotic participants were significantly different (P-allele = 0.002 and P-genotype = 0.012, respectively). Concerning rs6831280, ANCOVA found BMDs at LS 2-4 (L2-4) and total hip (TH) among the study subjects suffering from SOP with GA genotype were lower than in those carrying GG or AA (P-L2-4 = 0.004 and P-TH = 0.027, respectively).ConclusionsIDUA rs6831280 is associated with BMDs at L2-4 and TH in the elderly Chinese population with SOP and may serve as a marker for the genetic susceptibility to osteoporotic fractures.

Project description:BackgroundSevere gonadal steroid deficiency induces bone loss in adult men; however, the specific roles of androgen and estrogen deficiency in hypogonadal bone loss are unclear. Additionally, the threshold levels of testosterone and estradiol that initiate bone loss are uncertain.MethodsOne hundred ninety-eight healthy men, ages 20-50, received goserelin acetate, which suppresses endogenous gonadal steroid production, and were randomized to treatment with 0, 1.25, 2.5, 5, or 10 grams of testosterone gel daily for 16 weeks. An additional cohort of 202 men was randomized to receive these treatments plus anastrozole, which suppresses conversion of androgens to estrogens. Thirty-seven men served as controls and received placebos for goserelin and testosterone. Changes in bone turnover markers, bone mineral density (BMD) by dual-energy x-ray absorptiometry (DXA), and BMD by quantitative computed tomography (QCT) were assessed in all men. Bone microarchitecture was assessed in 100 men.ResultsAs testosterone dosage decreased, the percent change in C-telopeptide increased. These increases were considerably greater when aromatization of testosterone to estradiol was also suppressed, suggesting effects of both testosterone and estradiol deficiency. Decreases in DXA BMD were observed when aromatization was suppressed but were modest in most groups. QCT spine BMD fell substantially in all testosterone-dose groups in which aromatization was also suppressed, and this decline was independent of testosterone dose. Estradiol deficiency disrupted cortical microarchitecture at peripheral sites. Estradiol levels above 10 pg/ml and testosterone levels above 200 ng/dl were generally sufficient to prevent increases in bone resorption and decreases in BMD in men.ConclusionsEstrogens primarily regulate bone homeostasis in adult men, and testosterone and estradiol levels must decline substantially to impact the skeleton.Trial registrationClinicalTrials.gov, NCT00114114.FundingAbbVie Inc., AstraZeneca Pharmaceuticals LP, NIH.

Project description:ABSTRACT Most women do not qualify for pharmacologic osteoporosis treatment until more than a decade after menopause, by which time they will have lost up to 30% of their bone mass and may have already sustained fractures. Short or intermittent courses of bisphosphonate therapy, initiated around the time of menopause, might prevent excessive bone loss and lower long‐term fracture risk. We undertook a systematic review and meta‐analysis of randomized controlled trials (RCTs) to determine the effects of nitrogen‐containing bisphosphonates on fracture incidence, bone mineral density (BMD), and bone turnover markers in early menopausal women (ie, perimenopausal or <5 years postmenopausal) over ≥12 months. Medline, Embase, CENTRAL, and CINAHL were searched in July 2022. Risk of bias was evaluated using the Cochrane Risk of Bias 2 tool. Random effect meta‐analysis was undertaken using RevMan v5.3. In total, 12 trials were included (n = 1722 women); five evaluated alendronate, three risedronate, three ibandronate, and one zoledronate. Four were at low risk of bias; eight raised some concerns. Fractures were infrequent in the three studies that reported them. Compared with placebo, bisphosphonates improved BMD over 12 months (mean percentage difference, 95% confidence interval [CI]) at the spine (4.32%, 95% CI, 3.10%–5.54%, p < 0.0001, n = 8 studies), the femoral neck (2.56%, 95% CI, 1.85%–3.27%, p = 0.001, n = 6 studies), and the total hip (1.22%, 95% CI 0.16%–2.28%, p = 0.002, n = 4 studies). Over treatment durations of 24 to 72 months, bisphosphonates improved BMD at the spine (5.81%, 95% CI 4.71%–6.91%, p < 0.0001, n = 8 studies), femoral neck (3.89%, 95% CI 2.73%–5.05%, p = 0.0001, n = 5 studies) and total hip (4.09%, 95% CI 2.81%–5.37%, p < 0.0001, n = 4 studies). Bisphosphonates reduced urinary N‐telopeptide (−52.2%, 95% CI −60.3% to −44.2%, p < 0.00001, n = 3 studies) and bone‐specific alkaline phosphatase (−34.2%, 95% CI −42.6% to −25.8%, p < 0.00001, n = 4 studies) more than placebo at 12 months. This systematic review and meta‐analysis shows that bisphosphonates improve BMD and lower bone turnover markers in early menopause, warranting further investigation of these agents for osteoporosis prevention. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research. This systematic review and meta‐analysis of randomized controlled trials demonstrates that nitrogen‐containing bisphosphonates improve bone density and lower bone turnover markers in early menopausal women (i.e. perimenopausal or <5 year postmenopausal), warranting further investigation of these agents for osteoporosis prevention.

Dataset Information

Association of Adrenergic Receptor ?2A (?2A-AR) Gene rs1800544 Polymorphism with Bone Mineral Density and Bone Turnover Markers in an Elderly Chinese Population.

Publications

Association of Adrenergic Receptor α2A (α2A-AR) Gene rs1800544 Polymorphism with Bone Mineral Density and Bone Turnover Markers in an Elderly Chinese Population.

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