Polymorphism in vitamin D receptor is associated with bone mineral density in patients with adolescent idiopathic scoliosis

Low bone mass and osteopenia have been reported in the axial and peripheral skeleton of adolescent idiopathic scoliosis (AIS) patients. Furthermore, several recent studies have shown that gene polymorphisms are related to osteoporosis. However, no study has yet linked polymorphisms in the vitamin D receptor (VDR) gene and bone mass in AIS. Accordingly, the authors examined the association between bone mass and VDR gene polymorphisms in 198 girls diagnosed with AIS. The VDR BsmI (rs1544410), FokI (rs2228670) and Cdx2 (rs11568820) polymorphisms and bone mineral density at the lumbar spine (LSBMD) and femoral neck (FNBMD) were analyzed and compared to their levels in healthy controls. Mean LSBMD and FNBMD in AIS patients were lower than in age- and sex-matched healthy controls (P = 0.0022 and P = 0.0013, respectively). A comparison of genotype frequencies in AIS patients and controls revealed a significant difference for the BsmI polymorphism only (P = 0.0054). Furthermore, a significant association was found between the VDR BsmI polymorphism and LSBMD. In particular, LSBMD in AIS patients with the AA genotype was found to be significantly lower than in patients with the GA (P < 0.05) or GG (P < 0.01) genotypes. However, no significant association was found between LSBMD or FNBMD and the VDR FokI or Cdx2 polymorphisms. These results suggest that the VDR BsmI polymorphism is associated with LSBMD in girls with AIS.     

Association between vitamin D receptor gene polymorphisms and intervertebral disc degeneration: A meta-analysis

Background

Studies that have investigated the association between vitamin D receptor (VDR) gene polymorphisms and intervertebral disc degeneration (IDD) have yielded inconsistent results.

Coding region analysis of vitamin D receptor gene and its association with active calcium stone disease

The purpose of this study was to evaluate the impact of vitamin D receptor (VDR) gene polymorphisms on the status of active renal calcium stone formation. Male active renal calcium stone formers (ASF, final N = 106) with two episodes of stone relapse in the past 5 years were enrolled from December 2008 to April 2009. Controls (N = 109) were selected from age range- and gender-matched individuals who had no evidence or history of stone disease. Sequencing and single-strand conformational polymorphism were used to determine VDR polymorphisms in the patients and controls. Three polymorphisms were identified in the VDR gene: (1) start codon polymorphism (rs2228570T>C; p.M1T); (2) C/T polymorphism in the second intron (NT-029419.12: g.10416049C>T); (3) a silent polymorphism in exon 9 (rs731236T>C; p.I352I). Start codon polymorphism was the only one that was associated with the status of calcium stone formation (p < 0.05). We performed a complete coding genome analysis of VDR gene and observed that only start codon polymorphism was related to the status of active calcium stone formation.     

Association of vitamin D status with knee pain and radiographic knee osteoarthritis

Objective

The objective of the present study was to explore the association of serum vitamin D concentration and polymorphism in the vitamin D receptor (VDR), with knee pain and radiographic knee osteoarthritis (OA) among men and women in a large population-based UK cohort study.

Methods

Seven hundred and eighty-seven participants in the Hertfordshire Cohort Study (399 men, 388 women; mean age 65.6 ± 2.7 years) underwent a questionnaire on knee pain and radiographic knee examination. This study examined the association of Fok1, Cdx2 and Apa1 polymorphism in the gene for the VDR and serum 25(OH)D concentration with knee pain and radiographic knee OA by a generalized estimating equations population averaged logistic regression analysis in the Hertfordshire Cohort Study.

Results

There were no associations of Fok1, Cdx2 and Apa1 polymorphisms of the VDR with knee OA except for Aa for Apa1 compared with AA [Odds ratio (OR) 0.59, 95% confidence interval (CI) 0.36–0.95, P = 0.031]. While, ff for Fok1 (OR 1.60, 95% CI 1.07–2.39, P = 0.022) and AA for Cdx2 polymorphism (OR 2.21, 95% CI 1.07–4.56, P = 0.032) was significantly associated with higher prevalence of knee pain compared with FF for Fok1 and GG for Cdx2, respectively. None of these are statistically significant after adjusting for the three polymorphisms tested. 25(OH)D level was not significantly associated with radiographic knee OA, while, low tertile of 25(OH)D level tended to be associated with knee pain compared with high tertile of 25(OH)D level.

Conclusion

The present cross-sectional study using a large-scale population from the Hertfordshire Cohort study indicated that vitamin D may be associated with pain rather than radiographic change, but the evidence for an association between vitamin D genetic variation and pain in knee OA is very weak in the present study. Further replication of our results will be required to elucidate the association of vitamin D and knee OA.     

DNA Repair Gene and MTHFR Gene Polymorphisms as Prognostic Markers in Locally Advanced Adenocarcinoma of the Esophagus or Stomach Treated with Cisplatin and 5-Fluorouracil-Based Neoadjuvant Chemotherapy

Background  

DNA repair plays an important role in chemoresistance to platinum-based therapy, and therefore polymorphisms in the genes may modulate therapeutic response. We assessed 12 polymorphisms in 7 DNA repair genes and 2 polymorphisms in the MTHFR gene for association with disease response and prognosis.     

Associations between vitamin D receptor gene polymorphisms and ankylosing spondylitis in Chinese Han population: a case–control study

Summary

We assessed whether the vitamin D receptor gene polymorphisms (FokI, BsmI, ApaI, and TaqI) were associated with ankylosing spondylitis (AS) in a Chinese Han population. The TaqI polymorphism G allele was a risk factor in AS susceptibility.

Introduction

Previous studies have found that serum vitamin D levels are declined in patients with AS. The present study aims to evaluate the role of vitamin D receptor (VDR) gene polymorphisms in AS susceptibility in a Chinese Han population.

Methods

Four single nucleotide polymorphisms (SNPs) in the VDR gene (FokI (rs2228570), BsmI (rs1544410), ApaI (rs7975232), and TaqI (rs731236)) were genotyped by the improved multiplex ligase detection reaction (iMLDR) method in 620 AS patients and 620 geographically and ethnically matched healthy controls. Haplotypes were constructed after linkage disequilibrium (LD) analysis.

Results

Statistically significant difference was only found in the TaqI polymorphism between AS patients and controls. The TaqI polymorphism G allele was higher in AS group than that in controls (OR [95 % CI]?=?1.624 [1.122–2.352], χ ²?=?6.705, P?=?0.006). Linkage disequilibrium has been detected in TaqI and BsmI polymorphisms (D′?=?0.87, r ²?=?0.70). Two novel haplotypes (H1: AC and H2: GT) were significantly associated with the risk of AS, and they play protective and risk roles in AS morbidity, respectively.

Conclusions

The VDR gene TaqI polymorphism G allele may be a risk factor in AS susceptibility.

     

Genetic variants in the SOX6 gene are associated with bone mineral density in both Caucasian and Chinese populations

Summary  

Given the biological function of SOX6 and recent genome-wide association finding, we performed a fine-mapping association analyses to investigate the relationship between SOX6 and BMD both in Caucasian and Chinese populations. We identified many single-nucleotide polymorphisms (SNPs) within or near the SOX6 gene to be significantly associated with hip bone mineral density (BMD).     

Vitamin D receptor gene polymorphism predicts height and bone size,rather than bone density in children and young adults

Peak bone mass is considered to be under strong genetic control. We studied the association among anthropometry, bone density and vitamin D receptor (VDR) genotype in an ethnically homogeneous group of 148 Caucasian children and young adults. Bone density was measured by dual energy X-ray absorptiometry (DXA) and VDR genotype was determined by a direct haplotyping procedure of the BsmI, ApaI, and TaqI restriction fragment length polymorphisms. A second DXA measurement was made after approximately 4 years. Results are expressed as age- and sex-adjusted standard deviation scores (SDS). Previously, the collagen IA1 Sp1 polymorphism was studied in this population. We found VDR genotype to be associated with a 0.4 SDS increased height per allele copy of haplotype 3 (P = 0.04) and a 0.4 SDS increased width of the lumbar vertebral body in the haplotype 3 allele carriers (P = 0.05). We observed a trend towards a 0.3 SDS decreased bone mineral apparent density of lumbar spine (BMAD) per copy of haplotype 3 allele (P = 0.10). In contrast, no association with areal bone mineral density (BMD) was observed. In the follow-up analyses, no differences in height or bone gain among the VDR genotypes were demonstrated. By combining the risk alleles of VDR and collagen IA1 Sp1 genotype, an additive genotype effect on height (P = 0.006) and vertebral body width (P = 0.001) was found. In this exploratory study we found VDR genotype to be associated with frame size and BMAD. The VDR genotype effects on stature and bone size seem to neutralize the effect on areal BMD.     

Polymorphisms in the 5�� flank of COL1A1 gene and osteoporosis: meta-analysis of published studies

Summary  

A meta-analysis of studies was conducted involving 24,511 participants with 7,864 fractures in which polymorphisms in the 5′ flank of COL1A1 (rs1107946, rs2412298, and rs1800012) were related to osteoporosis phenotypes. Polymorphisms of all three sites were associated with BMD, and rs1800012 was associated with fracture but effect sizes were modest.     

Lifestyle predicts falls independent of physical risk factors

Summary  

Many falls occur among older adults with no traditional risk factors. We examined potential independent effects of lifestyle on fall risk. Not smoking and going outdoors frequently or infrequently were independently associated with more falls, indicating lifestyle-related behavioral and environmental risk factors are important causes of falls in older women.     

Gender‐specific association of methylenetetrahydrofolate reductase genotype and haplotype with the aggressiveness and prognosis of clear cell renal cell carcinoma in Japanese patients

OBJECTIVE

To determine if the two common polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene, C677T and A1298C, affect tumour aggressiveness or prognosis of clear cell renal cell carcinoma (CCRCC) in Japanese patients.

PATIENTS AND METHODS

MTHFR C677T and A1298C polymorphisms have been reported to cause decreased enzyme activity, which reduces the quantity of methyl groups available for DNA methylation and leads to mis‐incorporation of uracil into DNA, resulting in single‐strand DNA breaks. These effects might induce the accumulation of several genetic changes, leading to the development and progression of CCRCC. Therefore, we investigated the associations between MTHFR genotypes and haplotypes and the clinicopathological characteristics and survival rates in 240 Japanese patients with histopathologically confirmed CCRCC. MTHFR C677T and A1298C were genotyped and haplotypes were analysed using appropriate software.

RESULTS

The variant genotypes of MTHFR A1298C were significantly associated with some advanced characteristics of CCRCC in all patients, and these associations were stronger among men. However, among women, the variant genotypes of MTHFR C677T were associated with some advanced characteristics of CCRCC and the C677T variant genotypes or the 677T‐1298A haplotype was significantly associated with decreased overall survival (P = 0.007 and P = 0.009, respectively).

CONCLUSION

To our knowledge, this is the first report on the association between MTHFR polymorphisms and CCRCC aggressiveness or prognosis. These results suggest that the MTHFR genotypes and haplotype might be useful, in a gender‐specific manner, as predictive factors for the clinical course of CCRCC. Furthermore, these findings will contribute to the understanding of the mechanisms underlying CCRCC progression.     

Association of estrogen receptor alpha and collagen type I alpha 1 gene polymorphisms with bone mineral density in postmenopausal women

Summary  

In this study, ERα gene PvuII and XbaI polymorphisms and COL1A1 gene Sp1 polymorphisms in postmenopausal women were compared with lumbar vertebra and femoral neck BMD values. In conclusion, it was designated that PvuII polymorphism was effective on average lumbar vertebra BMD value in postmenopausal women of our study group.     

Role of MMP-3 and MMP-9 and Their Haplotypes in Risk of Bladder Cancer in North Indian Cohort

Purpose  

Matrix metalloproteinases (MMPs) play critical roles in cancer development and progression. Nonsynonymous single nucleotide polymorphisms (SNPs) in functional domain of MMP-3 and MMP-9 contribute appreciably to cancer predisposition and aggression. To test this proposition we examined whether six SNPs of the MMP-3 and MMP-9 genes are associated with risk of bladder cancer (BC) in a North Indian population.     

Vitamin D Receptor Polymorphisms and Falls Among Older Adults Living in the Community: Results From the ilSIRENTE Study

Vitamin D receptor (VDR) genotypes were associated with cognitive status, depressive symptoms, strength, and sarcopenia, but, thus far, no study has assessed their relationship with falls. The objective of this study is to evaluate whether, in a population of older adults living in the community, VDR FokI and BsmI genotypes are associated with falls. To this aim, we used data from the baseline evaluation of the ilSIRENTE study, which enrolled older adults ≥80 yr of age living in the community in Italy. Falls occurring within 90 days of assessment were assessed by study personnel. The mean age of 259 study participants was 85.0 ± 4.5 (SD) yr; 172 (66.4%) were women. Overall, 33 (12.7%) participants reported one or more falls. The rate of falls was 19.5% in participants with the BB genotype, 11.1% in those with Bb genotype, and 5.9% in those with bb genotype (p for linear trend = 0.02). After adjusting for potential confounders, compared with participants with the BB genotype, those with the bb genotype had a significantly lower OR for falls 0.14 (95% CI, 0.03–0.66). Rate of falls did not differ significantly across FokI genotypes (FF: 14.4%, Ff: 11.9%, ff: 9.1%; p = 0.43). In conclusion, the VDR bb genotype of the BsmI gene is associated with a reduced rate of falls compared with the BB genotype, whereas no effect on falls was shown for FokI polymorphism. Further studies conducted in larger population are needed to confirm the association of BsmI genotype and falls and to understand reasons for these findings.     

Vitamin D receptor initiation codon polymorphism, bone density and inflammatory activity of patients with ankylosing spondylitis

Objectives Osteoporosis is a common finding in ankylosing spondylitis (AS) and may contribute to spinal deformity and bone pain. Bone metabolism as well as inflammatory processes are influenced by the vitamin D receptor gene (VDR). We investigated initiation codon (FokI) and 3UTR (BsmI) polymorphisms of the VDR for whether there could be an association with bone mineral density (BMD) in relation to bone metabolism or inflammatory activity in patients with AS.Methods In this study, 104 patients with AS (m/w 71/33, mean age 41±12 years) were investigated for their lumbar and femoral BMD by DEXA and in part by QCT measurements and compared to 54 healthy controls. Disease activity indices, serum markers of bone metabolism and inflammation were recorded. FokI and BsmI polymorphisms of the VDR were genotyped using genomic DNA from peripheral leukocytes with present or absent restriction sites defined as alleles f and b or F and B, respectively.Results In male AS patients, FokI genotypes were significantly associated with spinal but not with femoral BMD values (P=0.01) as independent predictors of low BMD, which was also influenced by BMI, and inflammatory and pain indices. CRP and ESR values were also significantly associated with FokI genotypes. BMD in female patients showed no significant association with either FokI or BsmI genotypes of the VDR.Conclusion This is the first evidence that the VDR gene may be involved in BMD differences, bone metabolism and inflammatory processes in ankylosing spondylitis. A possible interaction of the vitamin D system, cytokines and bone could define new diagnostic and therapeutic implications in ankylosing spondylitis.     

Vitamin D receptor gene polymorphism and bone mineral density in 0–6-year-old Han children

This study aims to investigate the four vitamin D receptor (VDR) gene single nucleotide polymorphisms and their possible relationship with bone mineral density (BMD) in Chinese 0–6-year-old Han children. Two hundred four 0–6-year-old Han children without metabolic bone disease were randomly recruited in Shanghai, China. The BMD of the middle tibia was measured by an ultrasonic bone density instrument. VDR genotypes were determined by polymerase chain reaction restriction fragment length polymorphism using endonuclease ApaI, BsmI, TaqI and FokI. The alleles of a, T, b and F and the genotypes of aa, TT, bb and Ff were predominant. The frequency alleles of a, T, b and F were, respectively, 70.6, 95.8, 95.3 and 57.6%. When the influences of confounders such as serum 25(OH)D, serum zinc and outdoor activities on BMD were removed, the genotypes of BsmI and FokI were found apparently to be related to BMD. The BMD of the Bb carrier was much lower than that of the bb carrier (22.00 ± 27.84 and 43.14 ± 31.98, P < 0.05). The BMD of the ff carrier was lower than that of the Ff or FF carrier (26.97 ± 34.22 and 37.95 ± 29.70 and 53.52 ± 30.35, P < 0.001), while the genotypes of ApaI and TaqI have no relation with BMD in 0–6-year-old Han children. These findings show that the Bb and ff genotypes of the VDR BsmI and FokI variants are significantly associated with a decreased BMD in Chinese Han children aged 0–6 years, while the VDR ApaI and TaqI polymorphisms are not significantly associated with it.     

Association of Vitamin D Receptor Genetic Polymorphisms With Nephrolithiasis and End-Stage Renal Disease: A Meta-Analysis

BackgroundOur objective was to evaluate the association between vitamin D receptor (VDR) BsmI, FokI, TaqI, and ApaI gene polymorphisms and the risk of renal disease. A meta?analysis was conducted to determine the correlation between these VDR gene polymorphisms and the renal disease.MethodsMeta-analysis was carried out to clarify the association of BsmI (2467 cases and 2651 controls), FokI (2460 cases and 3085 controls), TaqI (3181cases and 3713 controls), and ApaI (2512 cases and 3091 controls) polymorphisms with nephrolithiasis (NL), diabetic nephropathy (DN), and end-stage renal disease (ESRD).ResultsThe VDR BsmI C allele, under the allele contrast random effect model, was associated with renal diseases calculated for ESRD. Subgroup analysis revealed association of VDR FokI polymorphism with ESRD and no association with NL and DN. The VDR TaqI C allele, under the allele contrast fixed effect model, was associated with renal diseases calculated collectively for DN, ESRD, and NL. Cochran's Q test showed no evidence of heterogeneity for TaqI and ApaI polymorphisms and showed a significant heterogeneity for BsmI and FokI polymorphisms.ConclusionsThis meta-analysis identifies BsmI, FokI, TaqI and ApaI polymorphisms of the VDR gene as risk factors for renal diseases.     

The cost of fall related presentations to the ED: A prospective,in-person,patient-tracking analysis of health resource utilization

Summary  

We prospectively collected data on elderly fallers to estimate the total cost of a fall requiring an Emergency Department presentation. Using data collected on 102 falls, we found the average cost per fall causing an Emergency Department presentation of 11,408. When hospitalization was required, the average cost per fall was11,408. When hospitalization was required, the average cost per fall was 29,363.     

Association between polymorphisms in vitamin D receptor gene and adolescent idiopathic scoliosis: a meta-analysis

Purpose

This meta-analysis was performed to clarify whether the two single nucleotide polymorphisms (ApaI and BsmI) in vitamin D receptor (VDR) gene conferred susceptibility to adolescent idiopathic scoliosis (AIS).

Methods

A comprehensive literature search in five online databases (PubMed, EMBASE, ISI Web of Science, CNKI, and Wanfang) was performed to identify studies that analyzed the association between VDR gene polymorphisms and risk of AIS. Observational studies met the predetermined inclusion criteria were selected for meta-analysis. The most appropriate genetic model was identified using a genetic model-free approach. Meta-analysis was performed using RevMan 5.3 software.

Results

Five eligible studies were included in this meta-analysis, which involved a total of 717 cases and 554 controls. A statistically significant association was observed between BsmI polymorphism and AIS (OR 1.90, 95% CI 1.32, 2.62). In subgroup analysis by ethnicity, the association between BsmI polymorphism and AIS was significant in Asians (OR 2.06, 95% CI 1.56, 2.73) but not in Caucasians (OR 0.70, 95% CI 0.23, 2.19). However, the ApaI polymorphism was not associated with AIS. Moreover, no evidence of association between BMD and the two VDR gene polymorphisms was detected.

Conclusions

Meta-analysis of existing data suggested that BsmI was associated with increased risk of AIS in Asian populations. Nevertheless, further studies with rigorous design and more ethnic groups are encouraged to validate our findings.

Graphical abstract

These slides can be retrieved under Electronic Supplementary Material.

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Diagnosis and treatment of osteoporosis before and after admission to long-term care institutions

Summary  

Bisphosphonate treatment rates were examined before and after admission to long-term residential care. Bisphosphonate treatment rates were low (16%) pre-admission but doubled after long-term residential care admission (30%). Men were very undertreated for osteoporosis, while a history of falls with injury was not associated with treatment.