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The aim of this study was to investigate the association of serum vitamin D, IL-4 levels and vitamin D receptor gene polymorphism in coronary artery disease with and without type 2 diabetes mellitus. Methods: The study was conducted in Department of Medicine and Department of Biochemistry, Maulana Azad Medical College and Lok Nayak Hospital, New Delhi. It involved two groups of patients suffering from CAD with type 2 diabetes mellitus (n =40) and CAD without type 2 diabetes mellitus (n =40). Blood sample was collected from all subjects using all aseptic precautions. The levels of serum 25-hydroxy Vitamin D were measured by Electrochemiluminescence Immunoassay. Expected normal serum values considered was 14-80ng/ml. Serum IL-4 had been measured by using commercially available ELISA kit provided by GEN- PROBE Diaclone, France. Expected normal serum value considered was < 98pg/ml. Results: The mean age of patients in different study groups were CAD with DM, 59.15± 9.31 years and CAD without DM, 58.1±9.51 years. Mean vitamin D levels were 18.6±8.3 ng/ml in CAD with DM and 23.4±9 ng/ml in CAD without DM. Mean IL-4 levels were 1.31±0.27pg/ml in CAD with DM group, 1.21±0.29pg/ml in CAD without DM group. The FF genotype of vitamin D receptor gene was present in 47.5 % of CAD with DM patients and 35 % of CAD without DM patients. The Ff genotype was present in 37.5 % of CAD with DM patients and 52.5 % of CAD without DM patients. The ff genotype was reported in 15 % of CAD with DM patients and 12.5 % of CAD without DM patients. Allele F of Vitamin D receptor gene constituted 66 % of total gene pool in CAD with DM patients and 61 % in CAD without DM patients. No significant association was observed with respect to the VDR FokI genotypes and cardiovascular outcomes. Conclusion: Serum Vitamin D levels were decreased in both groups of patients, more significantly decreased in the presence of DM in CAD patients. Serum IL-4 levels were significantly higher in CAD with DM group as compared to CAD without DM group. No associations could be found between Vitamin D receptor gene FokI polymorphism and risk of CAD in diabetic and non-diabetic individuals. No significant correlation was found between vitamin D and IL-4 levels in the patients of both groups. The association between VDR FokI polymorphism, vitamin D and inflammatory markers needs to be further explored in diabetic CAD patients.
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The Vitamin D receptor (VDR) gene encodes the VDR protein, which is essential for the effective realization of the physiological function of vitamin D. Low vitamin D levels in children and adolescents increase the risk of obesity, insulin resistance, high blood pressure or dyslipidemia.However, the mechanisms are still unclear.It was found that VDR gene single nucleotide polymorphisms (SNP), especially BsmI, affect the level of vitamin D in children and adolescents.Some common SNP, such as BsmI, ApaI, TaqI, Cdx2, are associated with the occurrence of obesity and metabolic syndrome(MS). However, these associations are not significant in some studies, especially in obese group or with rare SNP.This review focuses on the relationship between VDR gene polymorphisms and MS components in children and adolescents, in order to provide direction for early diagnosis and intervention of MS and even the necessity and effectiveness of vitamin D replacement therapy.
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Objective To investigate the relationship between single nucleotide polymorphism of vitamin D receptor (VDR) genes and osteoporosis in Chinese Northern Han patients with chronic obstructive pulmonary disease (COPD). Methods Patients with acute exacerbation COPD were enrolled and divided into osteoporosis and non-osteoporosis groups. Genomic DNA was extracted from peripheral blood of the subjects. UCSC genome browser and haploview 4.2 software were used to screen the tag single nucleotide polymorphism (tagSNPs) of VDR gene. The selected tagSNPs of VDR gene were genotyped by Sequenom MassARRAY SNP platform. Logistic regression was used to analyze the OR values and confidence intervals (CI) of each tagSNP in the codominant, dominant and recessive genetic models, and assess the relationship between single nucleotide polymorphisms in VDR gene and osteoporosis in COPD patients. Results A total of 379 COPD patients were enrolled. The group of osteoporosis and non-osteoporosis differed significantly in gender, age, alcohol assumption, peripheral platelet counts, serum phosphorus and serum creatinine levels (P<0.05). Finally, 17 tagSNPs of VDR gene (rs2238140 G/A, rs2228570 G/A, rs2408877 A/T, rs12721370 C/A, rs7299460 T/C, rs2239184 G/A, rs2239186 A/G, rs7136534 C/T, rs12721364 G/A, rs2853561 C/T, rs7965943 T/G, rs11168287 G/A, rs11608702 T/A, rs2239179 T/C, rs2189480 T/G, rs59707231 T/A, rs2853559 C/T) were filtered out for association analysis. Patients of rs2853561 carrying T/C and T/T genotypes had a lower risk of developing osteoporosis than those carrying C/C genotype in COPD patients (in dominant mode: T/C+T/T vs. C/C, OR=0.34, 95%CI 0.18-0.63, P=0.0003539) with statistical significance. Conclusions The present study has revealed significant relationship between rs2853561 of VDR gene and osteoporosis in patients with COPD. Further studies are needed to discover the mechanism of VDR gene polymorphism in the pathogenesis of osteoporosis in COPD.
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The Vitamin D receptor(VDR)gene encodes the VDR protein,which is essential for the effective realization of the physiological function of vitamin D. Low vitamin D levels in children and adolescents increase the risk of obesity,insulin resistance,high blood pressure or dyslipidemia. However,the mechanisms are still unclear. It was found that VDR gene single nucleotide polymorphisms(SNP),especially BsmI,affect the level of vitamin D in children and adolescents. Some common SNP,such as BsmI,ApaI,TaqI,Cdx2,are associated with the occurrence of obesity and metabolic syndrome(MS). However,these associations are not significant in some studies,especially in obese group or with rare SNP. This review focuses on the relationship between VDR gene polymorphisms and MS components in chil﹣dren and adolescents,in order to provide direction for early diagnosis and intervention of MS and even the necessity and effectiveness of vitamin D replacement therapy.
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Objective To study the correlation between VDR gene polymorphism and the transformation of bone markers in children with nephrotic syndrome and to observe whether active intervention treatment of vitamin D with nephrotic syndrome is influenced by VDR gene polymorphism. Methods We used polymerase chain reaction restriction fragment length polymorphism (PCR- RFLP) technology to detect the VDR genotypes of 70 children with nephrotic syndrome (one group received hormone for 2 weeks and the other received no hormone therapy) . Then we detected bone metabolism index among patients with nephrotic syndrome and 30 normal children (control group) and compared the index between the two groups with and without hormone therapy.We divided 70 children with nephrotic syndrome into the AA+Aa genotype group and the aa genotype group to study the difference between various genotypes of bone metabolism indexes. After retesting bone metabolism index of those children receiving the same dose of calcitriol therapy after 2 weeks, we divided them into three groups AA genotype, Aa genotype and aa genotype to detect the changes of bone metabolism index in different genotypes.Results (1) The calcitonin and serum phosphorus of children with AA+Aa genotype were significantly lower than those of childrenwith aa genotype (P＜ 0.05);25 (OH) D3 of children with aa genotype was significantly lower than that of ones with Aa + Aa genotype (P＜ 0.05) . (2) The changes of bone metabolism index in children with nephrotic syndrome after receiving the same dose of calcitriol for 2 weeks: the calcitonin and 25 (OH) D3 in AA+Aa genotype group were significantly higher after treatment (P＜0.05) .Conclusions Vitamin D receptor gene ApaⅠpolymorphism may be a genetic susceptibility factors affecting bone metabolic abnormalities. AA and Aa genotype may be a protective factor of bone metabolic abnormalities.The AA+Aa genetype of Vitamin D receptor gene ApaⅠpolymorphism response to treatment of calcitriol is positive.
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Objective To evaluate the relationship between vitamin D receptor(VDR) (rs731236)single nucleotide polymorphisms and genetic susceptibility to overweight/obesity in school-age children of Han and Kazakh in Xinjiang Uygur Autonomous Region.Methods The VDR gene rs731236 genotypes were detected by using polymerase chain reaction-restriction fragment length polymorphism method in 250 overweight/obesity school-age children(127Han,123 Kazakh) and 255 healthy controls(131 Han,124 Kazakh) as well.Results (1)There were statistically significant differences in the frequencies of rs731236 genotypes and alleles between the healthy controls of Han and Kazakh (x2 =9.904,P =0.005;x2 =9.312,P =0.002).(2)There were statistically significant differences in the frequencies of TT/Tt + tt genotype and the alleles between the overweight/obesity cases and healthy controls of Kazakh (x2 =3.891,P =0.049 ; x2 =5.871,P =0.015).But the difference in frequencies of rs731236 genotypes and alleles between the overweight/obesity cases and controls of Han were not statistically significant (x2 =0.064,P =0.800 ; x2 =0.190,P =0.663).(3)There were statistically significant differences in the frequencies of TT/Tt + tt genotype and alleles between the overweight/obesity cases and healthy controls of male school-age children of Kazakh (x2 =5.25,P =0.02;x2 =4.57,P =0.03),but the differences in frequencies of rs731236 genotypes and alleles between the overweight/obesity cases and controls were not statistically significant in female school-age children of Kazakh (x2 =0.06,P =0.80 ; x2 =1.40,P =0.24).There was no statistically significant difference in the frequencies of TT/Tt + tt genotype and alleles between the overweight/obesity cases and healthy controls of female school-age children of Han (x2 =0.04,P =0.84 ; x2 =0.04,P =0.84),and there was no statistically significant difference in male school-age children of Han(x2 =0.05,P=0.82;x2 =0.18,P=0.67).Conclusions VDR gene(rs731236)polymorphism bears ethnic diffe-rence.The polymorphisms of VDR gene polymorphism rs731236 are not associated with the susceptibility to overweight/obesity in school-age children of Han,while it is associated with the susceptibility to overweight/obesity school-age children in Kazakh,especially in male school-age children.
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0.05.[Conclusion]VDR TruⅠ and FokⅠpolymorphisms are not related to LDD in Han nationality.
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Recent studies have shown that environmental, biochemical, nutritional or genetic factors affect bone mineral density (BMD). The purpose of the present study was to investigate the effect of vitamin D receptor (VDR) gentotype and nutritional status on BMD of elderly women living in a rural area. Three hundred thirty five elderly women over 65 years in Asan participated the study. Data for demographic and nutrient intakes were obtained by survey with a two day 24 hr recall method. BMD was measured by broadband ultrasound attenuation (BUA) using quantitative ultrasound (QUS). VDR genotypes of the subjects analyzed with Bsm I restriction enzyme were bb (92%), Bb (7%) and BB (1%). No differences were found between genotypes bb and Bb/BB in age, menopausal age, body mass index and body fat. BUA of bb genotype was higher (62.5 +/- 15.6 dB/MHz) than Bb/BB genotype (56.1 +/- 17.6 dB/MHz) by Student's t-tests. Correlation analyses showed strong negative correlation of BMD and age, but positive correlation with BMI, energy and calcium intake. When subgroup analyses were conducted after stratification by the median calcium intake level (412.9 mg/d), the above median calcium intake group showed significant difference in BUA by VDR genotype while the lower median calcium intake group did not show significant difference. The current study confirmed interaction of calcium intake and VDR genotype in association with BMD. Further nutritional intervention will be needed to improve calcium status of the elderly women living in rural areas.
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Aged , Female , Humans , Adipose Tissue , Body Mass Index , Bone Density , Calcium , Genotype , Nutritional Status , Receptors, Calcitriol , Ultrasonography , Vitamin D , VitaminsABSTRACT
@#ObjectiveTo study the relationship between vitamin D receptor (VDR) gene polymorphism and calcitonin receptor (CTR) gene polymorphism, and bone mineral density (BMD) of the Han nationality woman in Hebei, explore the pathogenesis of osteoporosis (OP) at the gene level.MethodsPolymorphisms of VDR gene and CTR gene were analyzed by restriction fragment length polymorphisms (RFLPs) in 60 Han nationality women in Hebei.ResultsBb genetype of VDR had lower BMD values at all sites which were measured compared with bb genetype (P<0.05); CC genetype of CTR had tendency for lower BMD values at the L1～L4 compared with CT genetype (0.05<P<0.1); BMD value of CCBb genetype was the lowest.ConclusionBb genetype of VDR has a relationship with lower BMD. CCBb genetype can act as a heredity mark of OP in Chinese Han nationality woman.
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BACKGROUND: Genetic suggest that strongest effect is observed in the premenopausal peak bone mass, which become less with age. However, the evaluation of candidate genes polymorphisms has been most frequently done in postmenopausal women and the results have been controversial. Therefore, we studied the possible association of the peak bone mass and candidate for osteoporosis genes polymorphism in premenopausal women. METHODS: The associations between BMD and polymorphisms of the vitamin D receptor (3'-end region by BsmI restriction enzyme and start codon by FokI restriction enzyme), estrogen receptor (by PvuII and XbaI restriction enzyme), and type I collagen 1 (Sp1 binding site by MscI and BalI restriction enzyme) genes were examined in 100 healthy young Korean women who had a peak bone mass (age 20-35 years). Bone mineral densities were measured by dual energy X-ray absorptiometry (DEXA). Dietary calcium intake was also measured using a food frequency questionnaire. RESULTS: The frequencies of the B allele of the vitamin D receptor gene BsmI polymorphism and the X allele in the estrogen receptor gene, XbaI polymorphisms were lower in Koreans than those in Caucasians. The allelic frequencies of the vitamin vitamin D receptor gene FokI polymorphism and the estrogen receptor gene PvuII polymorphism were similar to those of Caucasians. No significant association was found between BMD and the vitamin D receptor genotype according to BsmI or FokI polymorphisms. There was also no significant relation between the PvuII or XbaI polymorphisms of the estrogen receptor gene and BMD. The associations between BMD and cross-genotypes combining the vitamin D receptor gene (BsmI and FokI) and estrogen receptor gene (PvuII and XbaI) polymorphisms were also analyzed. Among the subjects who lacked the Bf haplotype of the vitamin D receptor gene, the BMD of the femoral neck area was significantly higher in subjects lacking Px haplotypes of the estrogen receptor gene than in those having Px haplotype (p < 0.05). When dietary calcium intake was taken into consideration, there were significant differences in BMD according to the cross-genotype in the group having a low calcium intake (< 500 mg/day). The subjects that lacked the Bf and Px haplotypes had a significantly higher BMD in the femoral neck (p < 0.01), Ward's triangle (p < 0.05), and in the trochanteric area (p < 0.05) than those who lacked Bf but a Px haplotype. We did not find a polymorphism in the Sp1 binding site of the type I collagen 1 gene in our subjects. CONCLUSION: These data suggest that a complex interaction of vitamin D and the estrogen receptor gene with the dietary calcium intake, rather than a polymorphism of a single gene, may influence peak bone mass in healthy young Korean women.
Subject(s)
Female , Humans , Absorptiometry, Photon , Alleles , Binding Sites , Bone Density , Calcium , Calcium, Dietary , Codon, Initiator , Collagen Type I , Estrogens , Femur , Femur Neck , Genotype , Haplotypes , Osteoporosis , Polymorphism, Genetic , Surveys and Questionnaires , Receptors, Calcitriol , Vitamin D , VitaminsABSTRACT
BACKGROUND: Bone mineral density(BMD) is thought to be under genetic control. Polymorphisms at the vitamin D receptor(VDR) gene have recently been shown to contribute to the genetic variability in bone mineral density in Caucasians. However, the relationship between VDR-RFLP(restriction fragment length polymorphisms) and bone mineral density is controversial. METHODS: The VDR-RFLP by BsmI, ApaI, and TaqI were studied in 250(77 premenopausal, 173 postmenopausal) Korean women. Bone mineral densities at the lumbar spine(L2-L4), femoral neck, greater trochanter, and Wards triangle were measured by DEXA(Dual Energy X-ray Absorptiometry; Lunar DPX-L, U.S.A.). RESULTS: There were significant differences in VDR gene allele frequency when compared with those in Caucasians. The BsmI polymorphism was consisted of 0.8% BB homozygotes, 12.4% Bb heterozygotes, and 86.8% bb homozygotes. The ApaI polymorphism was 6.8% AA homozygotes, 42.0% Aa heterozygotes, and 51.2% aa homozygotes, and the TaqI polymorphism was 83.2% TT homozygotes, 16.8% Tt heterozygotes, and 0% tt homozygotes. When these three VDR-RFLP were combined, bbaaTT(51.2%), bbAaTT(29.6%), and BbAaTt(10.0%) were found to be most frequent types. There were no significant relationship between VDR-RFLP and BMD measured at the 2nd to 4th lumbar spine in all subjects. But there were significant relationship between VDR-RFLP and BMD at the proxmial femur in all subjects. Compared with bb or bbaaTT(or bbAaTT), women with the Bb or BbAaTt genotypes had significantly lower bone mineral densities at the proximal femur in all subjects. When we restricted the analysis to early postmenopausal women less than 10 years since menopause, these findings were more pronounced. CONCLUSION: These results suggest that VDR-RFLP may affect on BMD at the proximal femur in Korean women. However, the frequencies of B, A, and t alleles are very low in Korean women compared to those of Caucasians, further studies will be needed, with larger sample sizes.