Association of VDBP rs4701 variant, but not VDR/RXR-α over-expression with bone mineral density in pediatric β-Thalassemia patients (original) (raw)
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Journal of Nutrition & Food Sciences
Background: Vitamin D Receptor (VDR) gene variation may associate with dysfunctions of vitamin D. The aim of this study is to evaluate VDR variation and its relation with Bone Mineral Density (BMD) values in Beta-thalassemia. Methods: The children included in this study divided into two groups, 76 TM children, and 51 ages and sex matched healthy controls. All children subjected to full history taking, clinical examination. Liver and kidney functions, serum calcium, phosphorous, alkaline phosphatase and vitamin D levels measurement. BMD was determined. VDR rs2228570 SNP was assayed by real time PCR. Results: There was a significant increase in phosphorus, alkaline phosphatase, frequency of the TT genotype and T allele of rs2228570 SNP of VDR and decrease in calcium, vitamin D levels and BMD in patients group. There was a significant increase of vitamin D levels and decrease in patients with TT genotype than both TC and CC. Also, There were significant increase in number and % of osteopenia and osteoporosis in patients group with TT genotype than both TC and CC (p<0.001). Conclusion: TT genotype and T allele affect vitamin D level, function and associated with decrease BMD and high frequency of osteopenia and osteoporosis in children with Beta thalassemia.
Indian Journal of Hematology and Blood Transfusion, 2015
Vitamin D is critical for calcium, phosphate homeostasis and for mineralization of the skeleton, especially during periods of rapid growth. Vitamin D Deficiency leads to rickets (in children) and osteomalacia (in adults). Expression and activation of the vitamin D receptor (VDR) are necessary for the effects of vitamin D, in which several single nucleotide polymorphisms have been identified especially (FokI, BsmI). In this study serum 25 (OH) vitamin D3 levels were estimated by Enzyme Linked Immunosorbent Assay [ELISA], VDR (FokI, BsmI) gene polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism assay [PCR-RFLP].Serum levels of calcium, phosphorus, alkaline phosphatase and ferritin were determined in 50 Pediatrics beta thalassemia major patients and 60 controls. Patients had significantly lower serum calcium (p \ 0.001) lower serum vitamin D3 (p \ 0.001) with elevated levels of phosphorus (p \ 0.001) and alkaline phosphatase than controls (p = 0.04). Of the patients studied, 60 % had vitamin D deficiency (\20 ng/ml), 20 % had vitamin D insufficiency (21-30 ng/ml) and 20 % had sufficient vitamin D status ([30 ng/ml). Patients harboring mutant (Ff,ff) and wild (BB) genotypes were associated with lower serum calcium (p = 0.08, 0.02) respectively, lower vitamin D3 levels (p \ 0.001, 0.01) respectively. They were also suffering from more bony complications although the difference was not statistically significant (p [ 0.05). In conclusion, these results suggest that the VDR (FokI, BsmI) gene polymorphisms influence vitamin D status, (Ff,ff), BB genotypes had lower vitamin D levels, so they might influence risk of development of bone diseases in beta thalassemia major.
International Journal of Epidemiology, 2004
Vitamin D receptor (VDR) is a nuclear hormone receptor that acts as a transcriptional regulator in response to circulating 1,25 dihydroxyvitamin D 3 , the active hormonal form of vitamin D. VDR gene polymorphism (VDRGP) have been extensively studied in different diseases, with over 700 primary research articles, although this has focused mainly on the same markers. The VDRGP experience, with its huge literature and appearance of apparently contradictory reports each month, may provide an example of what to expect with other genes in the growing field of analysis of common gene polymorphisms with complex common disorders. Morita et al. provide a typical example of a moderately sized population study of the relationship of VDRGP to bone density and rate of bone loss in Japanese. 1 Reviewing the VDRGP literature is beyond the scope of this commentary which will only refer to a limited number of publications. For those interested, Zmuda et al. provide two comprehensive reviews of the literature of VDR related to disease. 2,3 Suffice to say that VDRGP have shown positive association to a wide range of divergent diseases, and due to the pleiotropic mode of action of a nuclear-hormone receptor such as the VDR, plausible molecular scenarios of involvement can be constructed for many different diseases. In fact, if functional genetic polymorphism occurs in a transcriptional regulator, one should expect pleiotropism, due to the fact that VDR controls the expression of a large and unknown number of subordinate genes, in both positive and negative senses and in cell-specific manners. The VDR protein is at the centre of the vitamin D endocrine system, a complex physiological system with substantial feedback regulatory mechanisms involved in maintaining serum calcium and 1,25 dihydroxyvitamin D3 within narrow bounds and now known to affect a large number of organs. 4 It is possible that the self-regulatory nature of the VDR endocrine system moderates the effect of VDRGP. VDR gene polymorphisms are looking for phenotypes, and judging from the literature, are related to numerous different traits, reflecting pleiotropism. Therefore, although literature has accumulated concerning VDR and bone mineral density (BMD) in particular, this may not necessarily be the most potent effect of genetic variation in VDR.
PubMed, 2019
Background Vitamin D deficiency is commonly identified in beta thalassemia major patients, related to iron accumulation.Vitamin D mediates its action upon binding to vitamin D receptor (VDR), a classical nuclear receptor. Several single nucleotide gene polymorphisms has been identified in VDR gene among which Bsml is commonly studied for its association with bone mineralisation and osteoporosis. Objective To explore the association between the Vitamin D Receptor Polymorphism (BsmI) and serum levels of Vitamin D, ionised Calcium, alkaline phosphatase in patients with beta thalassemia major. Method VDR gene was studied for Bsml polymorphisms from purified DNA in thirty six beta thalassemic patients (cases) - fourteen male and twenty two females, and thirty three controls after amplification by PCR followed by restriction digestion using appropriate restriction enzymes. Allelic differences between two groups were assessed by chi square and odds ratio test. Any potential link between the polymorphic variations and vitamin D status were assessed by post hoc ANOVA with bonferroni correction among the three genotypes. Result The distribution of BB genotype was significantly higher among the case groups (thalassemic group, χ2 = 9.77, p= 0.008). The odds ratio for the allele B was significantly higher in thalassemia group for a range of 1.97 to 5.94 for 95 percent cofidence interval (χ2 =10.4, p=0.0013). Serum Vitamin D, ionised Calcium were significantly low (p < 0.001) and Alkaline phosphatase (p < 0.001), was significantly high in thalassemics (cases). The genotype BB group had significantly low Vitamin D (p=0.001) and ionised Calcium (p < .001) compared to Bb and bb. The bb genotype had the highest levels of Vitamin D and ionised Calcium among the three genotypes. Conclusion The thalassemic patients are prone to Vitamin D deficiency and the superimposed predominance of BB genotype in them may be a risk factor for osteoporosis and cardiac dysfunction. Moreover, the study indicated genotype bb to have a probable protective role against Vitamin D deficiency in beta thalassemic patients.
Pediatric Endocrinology Diabetes and Metabolism
Aim of the study: The aim of this study was to assess the association between four vitamin D receptor (VDR) single nucleotide polymorphisms BsmI (rs1544410), ApaI (rs7975232), FokI (rs2228570) and TaqI (rs731236) and the susceptibility to chronic kidney disease (CKD) in Egyptian children and to evaluate their association with mineral status in these patients. Material and methods: The current study included 305 patients with CKD and 100 apparently healthy children. We measured the serum vitamin D (VD), parathyroid hormone (PTH) level and fibroblast growth factor 23 (FGF-23) levels by ELISA method. The genotyping of the four VDR gene variants was carried out by PCR-RFLP technique. Results: The TaqI AG & the BsmI TT genotypes were associated with a significantly higher risk of CKD. The expression of 25-OH D serum level was decreased in patients with TaqI GG & AG genotypes groups and in patients with BsmI TT genotype group The expression of PTH serum level was increased in patients with BsmI CT genotype group. The expression of FGF-23 serum level was increased in patients with Taq1 AG genotype group. We found 3 specific haplotypes; AGCA, AGCC and GGCA for healthy controls. Conclusions: Our study showed an association between VDR TaqI, BsmI polymorphisms and the susceptibility to CKD. The existence of VDR variants affected the protein expression of VD, FGF-23 and PTH. The AGCA, AGCC and GGCA haplotypes were considered as protective factors against the development of renal nephropathy in our population.
Journal of Applied Sciences Research, 2012
Objective: VDR gene polymorphisms and their functional significance and potential effects on disease susceptibility have been investigated. The present study was aimed to identify the genetic polymorphism of Vitamin D receptor in osteoporotic patients. Methods: Peripheral blood samples were obtained from 25 osteoporotic females and 25 healthy controls. All subjects were diagnosed by bone mineral density measurement. DNA was extracted and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed to identify VDR genes (FOKI and BSMI) polymorphism. Results: The frequencies of BB, Bb and bb genotypes (BSMI polymorphism) in (Osteoporotic patients) were 52%, 32% and 16% , respectively.While their frequency in controls was 12%, 24% and 64%, respectively. The BB genotype was higher in patients than in controls (P = 0.0000) while the bb genotype was significantly higher in controls than in patients. Regarding the FOKI polymorphism the frequencies of FF, Ff and ff genotypes in (Osteoporotic patients) were 68%, 12% and 20%, while their frequency in controls was 84%, 16% and 0%, respectively. Subjects carrying either B+ve or f+ve genotype were more risky to develop osteoporosis,(OR 9.33, 1.43) respectively. Conclusions: The BB genotype was higher in all patients than controls and the bb genotype is a protective genotype. The FF genotype was predominant among controls and ff genotype was associated with osteoporosis. Currently, however, the mechanisms by which VDR alleles regulate BMD remain poorly understood.
A comparative study of 25 hydroxy vitamin D levels in patients of thalassemia and healthy children
Pediatric Review: International Journal of Pediatric Research, 2016
Introduction: Vitamin D deficiency is emerging threat to patients with thalassemia. Adequate circulating levels of vitamin D are essential for optimal skeletal health and reducing fracture risk. The aim of this study was to evaluate the 25-OH-vitamin D levels in patients of thalassemia and compare its prevalence to healthy children. Methodology: In a case control study, 50 patients with beta thalassemia major (aged from 3 to 18 years) were compared with 50 sex and age matched children serves as a control group. Anthropometric measurement, Serum level of calcium, phosphorus, alkaline phosphatase, parathyroid hormone and 25-OH-vitamin D (25 hydroxycholecalciferol) were estimated for all patients & controls. Results: 25-OH-vitamin D deficiency was observed in 98% cases and 68% in control group. Difference in mean vitamin D levels between cases and controls was statistically significant (p<0.05). Weight and body mass index were significantly (p<0.05) lower in cases. Patient with beta thalassemia major compare to control had significantly (p<0.05) higher level of alkaline phosphatase and parathyroid hormone level. Conclusion: Thalassemia is associated with increased prevalence of 25-OH-vitamin D deficiency resulting in poor growth and quality of life in these children. This signifies the importance of therapeutic intervention.
The Journal of Clinical Endocrinology and Metabolism, 1997
Recent studies have suggested that genetic effects on bone mineral density (BMD) are related to allelic variation in the vitamin D receptor (VDR) gene. We examined 1) allelic influences of the VDR gene on BMD of the forearm, spine, hip, and whole body; and 2) allelic influences of the VDR gene on forearm BMD gain. Two hundred and seventy-three healthy boys and girls, aged 8.2-16.5 yr, at baseline were eligible. Forearm BMD was assessed with single photon absorptiometry at baseline. BMD gain was calculated as the annual percent change in BMD measured by single photon absorptiometry from the baseline and after 3.8 Ϯ 0.1 (ϮSD) yr. Calcium intake and physical activity were assessed by a detailed questionnaire at baseline and after 1 yr. VDR alleles were determined by BsaMI endonuclease
Vitamin D receptor alleles predict growth and bone density in girls
Archives of disease in …, 1998
Objectives-Polymorphism of the vitamin D receptor (VDR), collagen I type I (Col I I), and oestrogen receptor (ER) genes have been shown to account for some of the heritability of bone mineral density (BMD) in adults. This study examined this relation in prepubertal children. Methods and subjects-The relation between genotypes of VDR gene (Taq I, Bsm I, Fok I), Col I I gene (Msc I), and ER gene (Pvu II) with areal BMD, volumetric BMD, and growth were examined in 114 (68 girls) healthy 7 year old, white children. Results-The genotype of the VDR gene (Taq I) correlated with lumbar spine (L1-4) volumetric BMD in girls only, but at no other bone sites. In girls, VDR genotype aVected areal BMD at all sites. After adjusting for height and weight, however, this eVect was explained completely by the independent eVect of the VDR genotype on growth. Girls with genotype TT, were 3.9 kg heavier and 4.1 cm taller than those with tt, but this relation was not present at birth. No relation was found between genotypes of the VDR gene (Fok I), Col I I gene (Msc I), or ER gene (Pvu II) and BMD or growth variables. Conclusions-In prepubertal girls, VDR alleles contribute to lumbar spine volumetric BMD variance, but the areal BMD eVect reflects the relation between areal BMD and growth. VDR alleles might aVect postnatal growth regulation.
Relationship of vitamin D status and bone mass according to vitamin D-binding protein genotypes
Nutrition Journal, 2015
Background: Vitamin D-binding protein (DBP) may alter the biological activity of total 25-hydroxyvitamin D [25(OH)D]; this could influence on the effects of vitamin D in relation to bone mineral density (BMD) and fractures. Emerging data suggest that fetuin-A may be involved in bone metabolism. We aimed to investigate the influence of DBP gene polymorphism on the relationship of vitamin D status and fetuin-A levels to BMD and bone markers. Methods: This cross-sectional study was part of a health survey of employees of the Electricity Generating Authority of Thailand (1,734 healthy subjects, 72% male). Fasting blood samples were assayed for 25(OH)D, fetuin-A, N-terminal propeptides of type 1 procollagen (P1NP), C-terminal cross-linking telopeptides of type I collagen (CTx-I), and DBP rs2282679 genotypes. L1-L4 lumbar spine and femoral BMD were measured using dual-energy X-ray absorptiometry. Results: The DBP rs2282679 genotype distribution conformed to the Hardy-Weinberg equilibrium. There were no correlations between 25(OH)D levels and BMD and bone markers. But a trend of positive correlation was observed for the DBP genotypes with total hip BMD, and for the interaction between 25(OH)D and DBP genotypes with BMD at all femoral sites. We further analyzed data according to DBP genotypes. Only in subjects with the AA (common) genotype, 25(OH)D levels were positively related to BMD and bone markers, while fetuin-A was negatively related to total hip BMD, independently of age, gender and BMI. Conclusions: The interaction between vitamin D status, as measured by circulating 25(OH)D and DBP rs2282679 genotypes, modified the association between 25(OH)D and BMD and bone markers. Differences in DBP genotypes additionally influenced the correlation of fetuin-A levels with femoral BMD.