scholarly journals Evaluation of Association Studies and an Updated Meta-Analysis of VDR Polymorphisms in Osteoporotic Fracture Risk

2022 ◽  
Vol 12 ◽  
Author(s):  
Yi-yang Mu ◽  
Biao Liu ◽  
Bin Chen ◽  
Wang-fa Zhu ◽  
Xiang-Hua Ye ◽  
...  

Background: Several studies have examined the association between vitamin D receptor (VDR) polymorphisms and osteoporotic fracture risk; however, the results are not uniform. Furthermore, many new articles have been published, and therefore, an updated meta-analysis was performed to further explore these issues.Objectives: The aim of the study was to investigate the association between VDR, BsmI, ApaI, TaqI, FokI, and Cdx2 polymorphisms and osteoporotic fracture risk.Methods: The odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the association between VDR BsmI, ApaI, TaqI, FokI, and Cdx2 polymorphisms and the risk of osteoporotic fracture. We also used the false-positive reporting probability (FPRP) test and the Venice criteria to evaluate the credibility of the statistically significant associations.Results: Overall, this study found that the VDR ApaI and BsmI polymorphisms significantly increased the risk of osteoporotic fracture in European countries and America, respectively. However, when sensitivity analysis was performed after excluding low-quality and Hardy–Weinberg disequilibrium (HWD) studies, it was found that only individuals with the double-mutated genotype have an increased risk of osteoporotic fracture in European countries. In addition, when the credibility of the positive results was assessed, it was found that the positive results were not credible.Conclusion: This meta-analysis indicates that there may be no significant association among the polymorphisms of VDR BsmI, ApaI, TaqI, FokI, and Cdx2 and the risk of osteoporotic fracture. The increased risk of osteoporotic fracture is most likely due to false-positive results.

2018 ◽  
Vol 45 (1) ◽  
pp. 291-300 ◽  
Author(s):  
Lingmin Hu ◽  
Yue Zhang ◽  
Xing Wang ◽  
Lianghui You ◽  
Pengfei Xu ◽  
...  

Background/Aims: Whether maternal vitamin D deficiency is associated with gestational diabetes remains controversial. This meta-analysis aimed to systematically evaluate published evidence on the association between maternal vitamin D status and the risk of gestational diabetes. Methods: We retrieved relevant articles from the PubMed, Medline and Embase databases up to May 2017 for observational studies investigating the association between vitamin D status and the risk of gestational diabetes. Odds ratios (OR) or risk ratios (RR) from individual studies were pooled using the fixed and random effect models. Results: The meta-analysis of 29 observational studies included 28,982 participants, of which 4,634 were diagnosed with gestational diabetes, and showed that maternal vitamin D insufficiency was associated with a significantly increased risk of gestational diabetes by 39% (pooled OR = 1.39, 95%CI = 1.20-1.60) with moderate heterogeneity (I2 = 50.2%; P = 0.001). Moreover, the 25(OH)D level was significantly lower in gestational diabetes cases than in controls with a pooled effect of -4.79 nmol/L (95% CI = -6.43, -3.15). Significant heterogeneity was also detected (I2 = 65.0%, P < 0.001). Further subgroup analysis indicated that this association was also evident in most subpopulations. Conclusion: This meta-analysis indicated a significant association between vitamin D insufficiency and increased risk of gestational diabetes. Further well-designed large-scale clinical trials are essential to verify this association.


Author(s):  
Delia Nica-Badea ◽  
Aurelian Udristioiu

Background: Vitamin D has a widely acknowledged role in regulating the metabolism of calcium and phosphate, both essential to bone remodeling. However, numerous studies in recent decades have emphasized the association between low sun exposure and vitamin D deficiency, and an increased risk of extra-skeletal disorders such as cancer. Objective: This mini-review of literature aims to present an objective overview of several recent studies and meta-analyses evaluating the role of vitamin D in cancer prevention, its potential to improve cancer treatment outcomes, as well as the negative effects of vitamin D deficiencies. Methods: The antitumor effects of calcitriol and analogs in the treatment of cancer, either as single agents or in combination with other anticancer agents, are based on several mechanisms: inhibition of cancer cell proliferation and invasiveness, induction of differentiation and apoptosis, and promotion of angiogenesis, all recorded in a number of preclinical studies of several cancer types Results: The importance of VDR polymorphisms for individual malignancies remains a topic of debate. Contradictory effects have been recorded in recent studies, the results of which include positive associations of VDR when cumulated with other risk factors, both an increase and a decrease in cancer risks, as well as no correlation between VDR polymorphisms and individual malignancies.. Conclusion: The scientific evidence reviewed in this paper suggests that health care providers and individuals should consider increasing concentrations of 25 (OH) D through sensitive sun exposure and / or by supplementing with vitamin D to reduce cancer risk and, in combination with standard care, to treat cancer.


2018 ◽  
Vol 119 (3) ◽  
pp. 310-319 ◽  
Author(s):  
Christina Santamaria ◽  
Wei Guang Bi ◽  
Line Leduc ◽  
Negar Tabatabaei ◽  
Prévost Jantchou ◽  
...  

AbstractIn this systematic review and meta-analysis of observational studies, we aimed to estimate the associations between prenatal vitamin D status and offspring growth, adiposity and metabolic health. We searched the literature in human studies on prenatal vitamin D status and offspring growth in PubMed, up to July 2017. Studies were selected according to their methodological quality and outcomes of interest (anthropometry, fat mass and diabetes in offspring). The inverse variance method was used to calculate the pooled mean difference (MD) with 95 % CI for continuous outcomes, and the Mantel–Haenszel method was used to calculate the pooled OR with 95 % CI for dichotomous outcomes. In all, thirty observational studies involving 35 032 mother–offspring pairs were included. Vitamin D status was evaluated by circulating 25-hydroxyvitamin D (25(OH)D) level. Low vitamin D status was based on each study’s cut-off for low 25(OH)D levels. Low prenatal vitamin D levels were associated with lower birth weight (g) (MD −100·69; 95 % CI −162·25, −39·13), increased risk of small-for-gestational-age (OR 1·55; 95 % CI 1·16, 2·07) and an elevated weight (g) in infant at the age of 9 months (g) (MD 119·75; 95 % CI 32·97, 206·52). No associations were observed between prenatal vitamin D status and other growth parameters at birth, age 1 year, 4–6 years or 9 years, nor with diabetes type 1. Prenatal vitamin D may play a role in infant adiposity and accelerated postnatal growth. The effects of prenatal vitamin D on long-term metabolic health outcomes in children warrant future studies.


2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Muzaffer Ilhan ◽  
Bahar Toptas-Hekimoglu ◽  
Ilhan Yaylim ◽  
Seda Turgut ◽  
Saime Turan ◽  
...  

Objective. The genetic structural alterations in the majority of somatotroph adenomas are not clarified and the search for novel candidate genes is still a challenge. We aimed to investigate possible associations between vitamin D receptor (VDR) polymorphisms and acromegaly.Design, Patients, and Methods. 52 acromegaly patients (mean age45.7±1.9years) and 83 controls (mean age43.1±2.6years) were recruited to the study. VDR polymorphism was determined by polymerase chain reaction-based restriction fragment length polymorphism methods.Results. The distribution of VDR genotypes showed a significant difference in the frequencies of VDR FokI genotypes between patients and controls (P=0.034). VDR FokI ff genotype was significantly decreased in acromegaly patients (P=0.035) and carriers of FokI Ff genotype had a 1.5-fold increased risk for acromegaly (OR: 1.5, 95% CI: 1.07–2.1;P=0.020). IGF1 levels after treatment were significantly higher in patients carrying the Ff genotype compared to carrying ff genotype (P=0.0049). 25(OH)D3 levels were significantly lower in acromegaly patients (P<0.001).Conclusions. Our study suggests that VDR FokI genotypes might affect the development of acromegaly and VDR polymorphisms may play a role in the course of acromegaly as a consequence of altering hormonal status.


2010 ◽  
Vol 163 (3) ◽  
pp. 427-434 ◽  
Author(s):  
José Miguel Dora ◽  
Walter Escouto Machado ◽  
Jakeline Rheinheimer ◽  
Daisy Crispim ◽  
Ana Luiza Maia

ObjectiveThe type 2 deiodinase (D2) is a key enzyme for intracellular triiodothyronine (T3) generation. A single-nucleotide polymorphism in D2 (Thr92Ala) has been associated with increased insulin resistance in nondiabetic and type 2 diabetes (DM2) subjects. Our aim was to evaluate whether the D2 Thr92Ala polymorphism is associated with increased risk for DM2.Design and methodsA case–control study with 1057 DM2 and 516 nondiabetic subjects was performed. All participants underwent genotyping of the D2 Thr92Ala polymorphism. Additionally, systematic review and meta-analysis of the literature for genetic association studies of D2 Thr92Ala polymorphism and DM2 were performed in Medline, Embase, LiLacs, and SciELO, and major meeting databases using the terms ‘rs225014’ odds ratio (OR) ‘thr92ala’ OR ‘T92A’ OR ‘dio2 a/g’.ResultsIn the case–control study, the frequencies of D2 Ala92Ala homozygous were 16.4% (n=173) versus 12.0% (n=62) in DM2 versus controls respectively resulting in an adjusted OR of 1.41 (95% confidence intervals (CI) 1.03–1.94, P=0.03). The literature search identified three studies that analyzed the association of the D2 Thr92Ala polymorphism with DM2, with the following effect estimates: Mentuccia (OR 1.40 (95% CI 0.78–2.51)), Grarup (OR 1.09 (95% CI 0.92–1.29)), and Maia (OR 1.22 (95% CI 0.78–1.92)). The pooled effect of the four studies resulted in an OR 1.18 (95% CI 1.03–1.36, P=0.02).ConclusionsOur results indicate that in a case–control study, the homozygosity for D2 Thr92Ala polymorphism is associated with increased risk for DM2. These results were confirmed by a meta-analysis including 11 033 individuals, and support a role for intracellular T3 concentration in skeletal muscle on DM2 pathogenesis.


2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
Xue-Ren Gao ◽  
Yong-Guo Yu

The association between vitamin D receptor (VDR) polymorphisms (rs731236, rs1544410, rs2228570, and rs7975232) and the risk of autoimmune thyroid disease (AITD) had been investigated in previous studies. However, the results of these studies remained controversial. Thus, a meta-analysis was performed to derive a more precise conclusion. All related articles were systematically searched by PubMed, Embase, Google Scholar, and Chinese National Knowledge Infrastructure (CNKI). The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the strength of association. The overall results indicated thatVDRrs731236 and rs2228570 polymorphisms were significantly associated with a reduced risk of AITD. However, a stratification analysis based on clinical types showed thatVDRrs731236 and rs2228570 polymorphisms were associated only with a reduced risk of HT. A stratification analysis by ethnicity showed thatVDRrs731236 polymorphism was significantly associated with a reduced risk of AITD in Asian and African populations.VDRrs2228570 polymorphism was associated with a reduced risk of AITD in Asian populations.VDRrs1544410 polymorphism was associated with a reduced risk of AITD in European and African populations, but with an increased risk of AITD in Asian populations.VDRrs7975232 polymorphism was significantly associated with an increased risk of AITD in African populations. In conclusion, the present study suggested thatVDRrs731236, rs1544410, rs2228570, and rs7975232 polymorphisms were significantly associated with AITD risk. However, more well-designed studies should be performed to verify the current results.


Nutrients ◽  
2018 ◽  
Vol 10 (3) ◽  
pp. 277 ◽  
Author(s):  
Ren Zhou ◽  
Mengying Wang ◽  
Hui Huang ◽  
Wenyong Li ◽  
Yonghua Hu ◽  
...  

2015 ◽  
Vol 74 (11) ◽  
pp. 1958-1967 ◽  
Author(s):  
Andréa Marques ◽  
Ricardo J O Ferreira ◽  
Eduardo Santos ◽  
Estíbaliz Loza ◽  
Loreto Carmona ◽  
...  

2021 ◽  
Vol 3 (1) ◽  
pp. 02-09
Author(s):  
Qiaocong Chen ◽  
◽  
Huiling Lou ◽  
Cheng Peng

The risk of osteoporotic fracture can be viewed as a function of loading conditions and the ability of the bone to withstand the load. Skeletal loads are dominated by muscle action. Recently, it has become clear that bone and muscle share genetic determinants. Involvement of the musculoskeletal system manifests as bone loss (osteoporosis) and muscle wasting (sarcopenia). There is clinical evidence that osteoporotic fractures are significantly associated with sarcopenia, and sarcopenia may be a potential predictive factor for fracture risk, which suggests that there may be shared genetic determinants between sarcopenia and osteoporotic fracture. In recent years, genome-wide association studies (GWASs) studies have found that both lean mass and hand grip strength are associated with fracture risk, which may provide a possible endophenotype for elucidating the potential genetic study of fracture risk. Our effort to understand the clinical and genetic correlations between osteoporotic fracture and sarcopenia is helpful to understand the interaction between muscle and bone, and to study the etiology of complex musculoskeletal diseases. Identifying potentially important genetic variations in bone and muscle, measuring these variations using state-of-the-art technology, and replicating these experiments in humans and large animals will provide potential drug or intervention targets for osteoporotic fracture valuable in the future. Keywords: Genetics, osteoporosis, fracture, sarcopenia, genome-wide association studies, single nucleotide polymorphism


2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Sai Liu

Abstract Background Gestational diabetes mellitus (GDM) is a common disease during pregnancy. The association of vitamin D receptor (VDR) polymorphisms with GDM is still controversial. This study aimed to assess the associations between VDR polymorphisms and GDM risk. Methods We searched Cochrane Library, PubMed, and Embase electronic database for all eligible studies published from Jan 1, 1980 to December 31, 2020 to conduct a Meta-analysis. We analyzed four VDR polymorphisms: BsmI (rs1544410), ApaI (rs7975232), TaqI (rs731236), and FokI (rs2228570). Inclusion Criteria: (1) The data can be evaluated; (2) case–control study; and (3) meeting the Hardy–Weinberg’s law. Exclusion criteria: (1) Insufficient or extractable data; (2) Severe publication bias in the data; and (3) duplicate publications. We eventually included 15 studies in seven articles, including 2207 cases and 2706 controls. Results We eventually included 15 studies in seven articles, including 2207 cases and 2706 controls. The data showed that ApaI (rs7975232) VDR gene polymorphism was related with the risk of GDM for the comparison of CC vs AA and recessive model in overall population and FokI (rs2228570) VDR gene polymorphism was associated with the risk of GDM for recessive model in overall population. BsmI (rs1544410) polymorphism was not related with the risk of GDM in overall population. However, in the analysis of subgroups grouped by race, BsmI (rs1544410) has certain correlations. And, the data suggested the TaqI (rs731236) polymorphism was not associated with GDM. Conclusion Based on the meta-analysis, VDR ApaI (rs7975232) and FokI (rs2228570) polymorphisms increase susceptibility to GDM. In the future, it can be used to diagnose and screen molecular biomarkers for GDM patients.


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