Dataset Information

Association of Vitamin D Receptor Polymorphisms With Activity of Acromegaly, Vitamin D Status and Risk of Osteoporotic Fractures in Acromegaly Patients.

ABSTRACT: Introduction: The vitamin D receptor (VDR) gene is one of the most widely studied tumorigenesis-related genes. The primary objective of this study was assessment of possible roles of VDR gene polymorphisms in acromegaly, with regard to the activity of the disease and compared them with a control group. Furthermore, we have assessed the associations between these polymorphisms with vitamin D status as well as with TBS (trabecular bone score) and risk for osteoporotic fracture in acromegaly patients. Materials and Methods: We studied 69 patients with acromegaly and 51 healthy controls (CG). Acromegaly patients were divided into three subgroups on the basis of disease activity (AA, active acromegaly; CD, controlled disease; CA, cured acromegaly). In all patients, blood samples were obtained to assess the hormonal and metabolic status as well as genetic analysis. VDR polymorphisms were determined by means of two methods, Polymerase Chain Reactions (PCR) and minisequencing (SNaPshot). Results: Genotype frequencies for VDR ApaI, TaqI, BsmI, and FokI polymorphisms did not deviate significantly from Hardy-Weinberg equilibrium (HWE) in the acromegaly group as well as in the control group. There was no statistically significant difference in distributions of these four VDR genotypes between acromegaly patients and the control group. This study revealed statistically significant negative correlation between risk of major osteoporotic fractures and genotypes tt (TaqI), aa (ApaI) and bb (BsmI) in acromegaly groups. Furthermore, the negative correlations were observed between TBS and risk for major osteoporotic fractures and hip fractures. Conclusions: Our study suggests that tt (TaqI), aa (ApaI) and bb (BsmI) of VDR gene may be associated with better bone quality and microarchitecture (higher TBS), which lead to a lower risk of osteoporotic fractures in acromegaly patients. TBS may be a useful tool for predicting risk of fractures in acromegaly patients.

SUBMITTER: Jawiarczyk-Przybylowska A

PROVIDER: S-EPMC6768940 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Association of Vitamin D Receptor Polymorphisms With Activity of Acromegaly, Vitamin D Status and Risk of Osteoporotic Fractures in Acromegaly Patients.

Jawiarczyk-Przybyłowska Aleksandra A Halupczok-Żyła Jowita J Kolačkov Katarzyna K Gojny Łukasz Ł Zembska Agnieszka A Bolanowski Marek M

Frontiers in endocrinology 20190924

Introduction: The vitamin D receptor (VDR) gene is one of the most widely studied tumorigenesis-related genes. The primary objective of this study was assessment of possible roles of VDR gene polymorphisms in acromegaly, with regard to the activity of the disease and compared them with a control group. Furthermore, we have assessed the associations between these polymorphisms with vitamin D status as well as with TBS (trabecular bone score) and risk for osteoporotic fracture ...[more]

PMID: 31616375

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Project description:ObjectivePrevious epidemiological studies have found an association between serum cholesterol level and bone mineral density. However, epidemiological studies evaluating the association between serum cholesterol level and the incidence of osteoporotic fracture are scant. Therefore, the objective of this study was to investigate whether serum cholesterol levels in Chinese participants aged 55?years or older was associated with an increased risk of osteoporotic fracture.Materials and methodsWe performed a cross-sectional study, including 1,791 participants (62.1% postmenopausal women and 213 fractures). Standardized self-administered questionnaires, physical examination, laboratory tests, and dual-energy X-ray absorptiometry examination were performed. Multivariate-adjusted logistic regression models were used to evaluate associations between serum cholesterol [total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL-C), and low-density lipoprotein (LDL-C)] levels and the osteoporotic fracture risk.ResultsAfter adjusting for potential confounding factors, there were no associations between per SD increase in TC and LDL level and an increased risk of osteoporotic fracture in total participants, and in men and women as individual groups. There was a significant association between per SD increase in HDL-C level and an increased risk of osteoporotic fracture in total participants [odds ratios (OR) 1.20, 95% confidence interval (CI) 1.03, 1.40, P?=?0.023] and in women (OR 1.37, 95% CI 1.12, 1.68, P?=?0.003), whereas no association was observed in men (OR 1.01, 95% CI 0.73, 1.40, P?=?0.951). Additionally, we found a significant association between per SD increase in TG level and an increased risk of osteoporotic fracture in total participants (OR 1.20, 95% CI 1.04, 1.38, P?=?0.015). In women, a nonlinear relationship was observed between per SD increase in TG level and an increased risk of osteoporotic fracture. The risk of osteoporotic fracture in women increased with TG level >1.64?mmol/L (OR 1.93, 95% CI 1.24, 3.00, P?=?0.004).ConclusionAmong Chinese older adults, serum HDL-C level is significantly associated with a risk of osteoporotic fractures in women, and serum TG level is significantly associated with a risk of osteoporotic fractures in total participants and in women with TG >1.64?mmol/L.

Project description:Osteoporotic fractures are a leading cause of disability, costs, and mortality. FRAX is a tool used to assess fracture risk in the general population. Mental disorders and medications to treat them have been reported to adversely affect bone health, but, to date, they have not been systematically studied in relation to osteoporotic fractures.To examine the association of mental disorders and psychotropic medication use with osteoporotic fracture risk in routine clinical practice.In this population-based cohort study, bone mineral density and risk factors were used to calculate FRAX scores using data from the Manitoba Bone Density Program database of all women and men 40 years of age or older in Manitoba, Canada, referred for a baseline dual-energy x-ray absorptiometry scan from January 1, 1996, to March 28, 2013. Population-based health services data were used to identify primary mental disorders during the 3 prior years, psychotropic medication use during the prior year, and incident fractures. Cox proportional hazards regression models estimated the risk for incident fractures based on mental disorders and use of psychotropic medications. Data analysis was conducted from November 25, 2013, to October 15, 2016.Incident nontraumatic major osteoporotic fractures (MOFs) and hip fractures.Of the 68?730 individuals (62?275 women and 6455 men; mean age, 64.2 [11.2] years) in the study, during 485?322 person-years (median, 6.7 years) of observation, 5750 (8.4%) sustained an incident MOF, 1579 (2.3%) sustained an incident hip fracture, and 8998 (13.1%) died. In analyses adjusted for FRAX score, depression was associated with MOF (adjusted hazard ratio [aHR], 1.39; 95% CI, 1.27-1.51; P?<?.05) and hip fracture (aHR, 1.43; 95% CI, 1.22-1.69; P?<?.05) before adjustment for medication use, but these associations were not significant after adjustment for medication use. In contrast, the use of selective serotonin reuptake inhibitors (aHR for MOF, 1.43; 95% CI, 1.27-1.60; P?<?.05; aHR for hip fracture, 1.48; 95% CI, 1.18-1.85; P?<?.05), antipsychotics (aHR for MOF, 1.43; 95% CI, 1.15-1.77; P?<?.05; aHR for hip fracture, 2.14; 95% CI, 1.52-3.02; P?<?.05), and benzodiazepines (aHR for MOF, 1.15; 95% CI, 1.04-1.26; P?<?.05; aHR for hip fracture, 1.24; 95% CI, 1.05-1.47; P?<?.05) were each independently associated with significantly increased risk for both MOF and hip fracture. FRAX significantly underestimated the 10-year risk of MOF by 29% and of hip fracture by 51% for those with depression. It also underestimated the 10-year risk of MOF by 36% for use of selective serotonin reuptake inhibitors, by 63% for use of mood stabilizers, by 60% for use of antipsychotics, and by 13% for use of benzodiazepines. FRAX underestimated the 10-year risk of hip fracture by 57% for use of selective serotonin reuptake inhibitors, by 98% for use of mood stabilizers, by 171% for use of antipsychotics, and by 31% for use of benzodiazepines. FRAX correctly estimated fracture risk in people without mental disorders and those not taking psychotropic medications.Mental disorders and medication use were associated with an increased risk for fracture, but in simultaneous analyses, only medication use was independently associated with fracture. Depression and psychotropic medication use are potential risk indicators that are independent of FRAX estimates.

Project description:As life expectancy increases, the prevalence of osteoporosis is increasing. In addition to vitamin D which is well established to have an association with osteoporosis, B vitamins, such as thiamine, folate (vitamin B9), and cobalamin (vitamin B12), could affect bone metabolism, bone quality, and fracture risk in humans by influencing homocysteine/folate metabolism. Despite the crucial role of B vitamins in bone metabolism, there are few studies regarding associations between B vitamin-related genes and osteoporosis. In this study, we investigated the genetic association of four single nucleotide polymorphisms (SNPs) within the 3'-untranslated regions of vitamin B-related genes, including TCN2 (encodes transcobalamin II), CD320 (encodes transcobalamin II receptor), SLC19A1 (encodes reduced folate carrier protein 1), and SLC19A2 (encodes thiamine carrier 1), with osteoporosis and osteoporotic vertebral compression fracture (OVCF). We recruited 301 postmenopausal women and performed genotyping of CD320 rs9426C>T,TCN2 rs10418C>T, SLC19A1 rs1051296G>T, and SLC19A2 rs16862199C>T using a polymerization chain reaction-restriction fragment length polymorphism assay. There was a significantly higher incidence of both osteoporosis (AOR 5.019; 95% CI, 1.533-16.430, p < 0.05) and OVCF (AOR, 5.760; 95% CI, 1.480-22.417, p < 0.05) in individuals with genotype CD320 CT+TT and high homocysteine concentrations. Allele combination analysis revealed that two combinations, namely CD320 C-TCN2 T-SLC19A1 T-SLC19A2 C (OR, 3.244; 95% CI, 1.478-7.120, p < 0.05) and CD320 T-TCN2 C-SLC19A1 G-SLC19A2 C (OR, 2.287; 95% CI, 1.094-4.782, p < 0.05), were significantly more frequent among the osteoporosis group. Our findings suggest that SNPs within the CD320 gene in 3´-UTR may contribute to osteoporosis and OVCF occurrences in some individuals. Furthermore, specific allele combinations of CD320, TCN2, SLC19A1, and SLC19A2 may contribute to increased susceptibility to osteoporosis and OVCF.

Dataset Information

Association of Vitamin D Receptor Polymorphisms With Activity of Acromegaly, Vitamin D Status and Risk of Osteoporotic Fractures in Acromegaly Patients.

Publications

Association of Vitamin D Receptor Polymorphisms With Activity of Acromegaly, Vitamin D Status and Risk of Osteoporotic Fractures in Acromegaly Patients.

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