Association of vitamin D receptor gene polymorphism with the risk of systemic lupus erythematosus

Abstract

Relationship between vitamin D receptor (VDR) gene polymorphism and the risk of systemic lupus erythematosus (SLE) from the published reports are still conflicting. This study was conducted to evaluate the relationship between VDR BsmI (rs1544410), Fok1 (rs2228570), ApaI (rs7975232) and TaqI (rs731236) gene polymorphism and the risk of SLE using meta-analysis method. The association studies were identified from PubMed and Cochrane Library on 1 March 2014, and eligible investigations were included and synthesized using meta-analysis method. Thirteen reports were recruited into this meta-analysis for the association of VDR gene polymorphism with SLE susceptibility. In this meta-analysis for overall populations, the BsmI B allele and bb genotype, Fok1 f allele and ff genotype, and ApaI aa genotype, were associated with the risk of SLE. In Asians, the BsmI B allele, BB genotype and bb genotype, Fok1 f allele and ff genotype were associated with the risk of SLE. In Africans, the BsmI B allele, BB genotype and bb genotype, Fok1 f allele and ff genotype, ApaI A allele, AA genotype and aa genotype were associated with the risk of SLE. However, VDR BsmI, Fok1, ApaI and TaqI gene polymorphism were not associated with the risk of SLE in Caucasians. In conclusion, the BsmI B allele and bb genotype, Fok1 f allele and ff genotype were associated with the risk of SLE in overall populations, and in Asians, but these associations were not found in Caucasians. However, more studies should be conducted to confirm it.     

The association between BsmI variant of vitamin D receptor gene and susceptibility to tuberculosis

Vitamin D receptor (VDR) gene variants may play a key role in the susceptibility to tuberculosis (TB). We have investigated the association BsmI, TaqI, FokI polymorphisms in the VDR gene with susceptibility to tuberculosis. This study included 128 patients with TB (pulmonary and extrapulmonary TB) and 80 healthy subjects living in Istanbul, Turkey. Genetic polymorphisms were studied by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques at genomic DNA isolated from whole blood-EDTA. The present study results indicate that the genotype and allele frequencies for patient group (BB:22, Bb:53, bb:25; B allele:48%, b allele:52%) was significantly different from the control group (BB:6, Bb:48, bb: 46; B allele:30 b allele:70) due to an overrepresentation of B allele (P: 0.000 OR: 1.61 95% 1.23–2.11). However there were no significant differences in distribution of allele/genotype frequencies of FokI, TaqI variants between TB and healthy controls. This study results suggest that BsmI variant of VDR gene may play an important role in susceptibility to tuberculosis.     

Association of vitamin D receptor BsmI (rs1544410) gene polymorphism with the intact parathyroid hormone (iPTH) level among patients with end-stage renal disease

Abstract

Association of vitamin D receptor (VDR) BsmI (rs1544410) gene polymorphism with the intact parathyroid hormone (iPTH) level among patients with end-stage renal disease (ESRD) from the published reports is still conflicting. This meta-analysis was performed to evaluate the relationship between VDR BsmI (rs1544410) gene polymorphism and the iPTH level among patients with ESRD. The association studies were identified from PubMed, and Cochrane Library on 1 March 2014, and eligible investigations were included and synthesized using meta-analysis method. Six reports were recruited into this meta-analysis for the association of VDR BsmI gene polymorphism with iPTH level among patients with ESRD. In this meta-analysis, the iPTH level in ESRD patients carrying BsmI Bb genotype was higher than that in ESRD patients carrying bb genotype in overall populations (Bb versus bb: OR?=?61.40, 95% CI: 19.65–103.16, p?=?0.004). However, the iPTH level in ESRD patients carrying BB genotype was not significant different from that in ESRD patients with Bb genotype and bb genotype in overall populations (BB versus Bb: OR?=??18.30, 95% CI: ?126.28–89.69, p?=?0.74; BB versus bb: OR?=?22.85, 95% CI: ?70.81–116.51, p?=?0.63). Furthermore, the results for Caucasians were similar to those in overall populations. In conclusion, the iPTH level in ESRD patients carrying BsmI Bb genotype was higher than that in ESRD patients carrying bb genotype in overall populations and in Caucasians. However, more studies should be conducted to confirm it.     

Role of vitamin D receptor gene polymorphisms and serum 25-hydroxyvitamin D level in Egyptian female patients with systemic lupus erythematosus

Recently, several studies have demonstrated the role of vitamin D receptor (VDR) polymorphisms in the development of systemic lupus erythematosus (SLE). We aimed to evaluate VDR (ApaI, BsmI, and FokI) gene polymorphisms and haplotypes as a risk factors and/or activity markers for SLE, and whether they influence 25-hydroxyvitamin (25(OH) D) level. One hundred and seven SLE patients and 129 controls were enrolled in this study. Disease activity in SLE patients was assessed using Disease Activity Index. Polymorphisms of VDR gene were detected using polymerase chain reaction restriction fragment length polymorphism. Serum 25(OH) D levels were measured using ELISA. We found that ApaI AA genotype, BsmI B allele, Bb, BB genotypes, FokI F allele and FF genotype frequencies of VDR were increased in SLE group. There were significant associations of VDR ApaI AA, BsmI BB, and FokI FF genotypes with lupus nephritis and higher SLE activity scores. Moreover, serum 25(OH) D levels were increased in SLE patients carrying FokI ff genotype compared with patients carrying FF genotype. VDR haplotypes aBF and ABF were associated with SLE risk. The ABF haplotype was associated with higher SLE activity scores and lower serum 25(OH) D concentrations. We observed that the presence of leuko/lymphopenia, renal disorders, higher SLE activity scores and higher anti-dsDNA levels were accompanied by a significant decrease of serum 25(OH)D concentrations. We concluded that The VDR genes polymorphisms, haplotypes, and decreased 25(OH) D levels were associated with risk and more activity scores of SLE.     

BsmI polymorphisms in vitamin D receptor gene are associated with diabetic nephropathy in type 2 diabetes in the Han Chinese population

We investigated the relationship between BsmI/ApaI polymorphisms in vitamin D receptor gene and diabetic nephropathy in a Han Chinese population. PCR-restriction fragment length polymorphism was used to test the genotype and allele frequency of BsmI and ApaI polymorphisms in 304 patients with type 2 diabetes mellitus (DM group) and 100 control individuals (ND group). The DM group was further divided into DN0 (no diabetic nephropathy), DN1 (diabetes with small amount of albuminuria), DN2 (diabetes with large amount of albuminuria), L/NDN (late-onset DN after 5 years/no DN over the whole follow-up period of 5 years) and EDN (early-onset diabetic nephropathy occurring within first year) subgroup. We found that (1) genotype and allele frequency of BsmI polymorphism had significant difference between DM and ND group; BB+Bb genotype and B allele frequency were significantly higher in DN2 group than in ND and DN0 group; the ApaI polymorphism and allele frequency did not show any difference between DM and ND group; (2) BsmI BB+Bb genotype and B allele frequency were significantly higher in EDN group than in L/NDN group; (3) among patients with nephropathy, albumin excretion rate (AER) in 24-hour urine was significantly higher in those with BB+Bb phenotype than in those with bb phenotype (P<0.01), (4) unconditional logistic regression analysis showed that BsmI BB+Bb genotype was not only correlated with type 2 diabetic nephropathy, but also correlated with early-onset type 2 diabetic nephropathy. We conclude that the allele B (BB or Bb genotype) in vitamin D receptor gene is correlated with large amount albuminuria in the Han Chinese population with type 2 diabetes, and is probably a risk factor for early-onset diabetic nephropathy.     

Associations between vitamin D receptor polymorphisms and susceptibility to rheumatoid arthritis and systemic lupus erythematosus: a meta-analysis

The aim of this study was to determine whether the vitamin D receptor (VDR) polymorphisms confer susceptibility to rheumatoid arthritis (RA) and systemic lupus erythematous (SLE). A meta-analysis was conducted on the associations between the BsmI, TaqI, FokI, and ApaI polymorphisms of VDR and RA or SLE using: (1) allele contrast, (2) the recessive model, (3) the dominant model, and (4) additive model. A total of ten studies, six RA and four SLE studies, were considered in the meta-analysis. Meta-analysis of the VDR BsmI and TaqI polymorphisms showed no association between RA in all subjects, or in European or Asian subjects. In contrast, meta-analysis of the F allele, the FF genotype, and the FF vs. the ff genotype of the FokI polymorphism showed significant associations with RA in Europeans. The overall OR of the association between the F allele and RA was 1.502 (95% CI = 1.158–1.949, P = 0.002). Meta-analysis of the B allele, BB + Bb genotype, and BB genotype (additive model) of the BsmI polymorphism showed significant associations with SLE and LN in Asians. The overall ORs of the associations between the B allele and SLE and LN were 3.584 (95% CI = 1.407–9.130, P = 0.007) and 3.652 (95% CI = 1.347–9.902, P = 0.011). This meta-analysis demonstrates that the VDR FokI polymorphism may confer susceptibility to RA in Europeans. Furthermore, associations were found between the VDR BsmI polymorphism and susceptibilities to SLE and LN in Asians.     

Association of vitamin D receptor BsmI (rs1544410) gene polymorphism with the chronic kidney disease susceptibility

Abstract

Association of vitamin D receptor (VDR) BsmI (rs1544410) gene polymorphism with the chronic kidney disease (CKD) susceptibility from the published reports are still conflicting. This meta-analysis was performed to evaluate the relationship between VDR BsmI (rs1544410) gene polymorphism and the risk of CKD. The association studies were identified from PubMed, Cochrane Library and China Biological Medicine Database on 1 March 2014, and eligible investigations were included and synthesized using meta-analysis method. Nine reports were recruited into this meta-analysis for the association of VDR BsmI gene polymorphism with CKD susceptibility. In this meta-analysis for overall populations, the BsmI B allele BB genotype and bb genotype were not associated with the risk of CKD (B allele: OR?=?1.12, 95% CI: 0.88–1.44, p?=?0.36; BB genotype: OR?=?1.15, 95% CI: 0.81–1.62, p?=?0.43; bb genotype: OR?=?0.86, 95% CI: 0.61–1.20, p?=?0.36). Furthermore, VDR BsmI gene polymorphism was not associated with CKD susceptibility in Asians and in Caucasians. In conclusion, the BsmI gene polymorphism was not associated with CKD susceptibility in overall populations, in Asians and in Caucasians. However, more studies should be conducted to confirm it.     

Association of Vitamin D Receptor BsmI Gene Polymorphism with Risk of Tuberculosis: A Meta-Analysis of 15 Studies

Background

Genetic variations in vitamin D receptor (VDR) may contribute to tuberculosis (TB) risk. Many studies have investigated the association between VDR BsmI gene polymorphism and TB risk, but yielded inconclusive results.

Methodology/Principal Findings

We performed a comprehensive meta-analysis of 15 publications with a total of 2309 cases and 3568 controls. We assessed the strength of the association between VDR BsmI gene polymorphism and TB risk and performed sub-group analyses by ethnicity, sample size and Hardy–Weinberg equilibrium (HWE). We found a statistically significant correlation between VDR BsmI gene polymorphism and decreased TB risk in four comparison models: allele model (b vs. B: OR = 0.78, 95% CI = 0.67, 0.89; P_{heterogeneity} = 0.004), homozygote model (bb vs. BB: OR = 0.61, 95% CI = 0.43, 0.87; P_{heterogeneity} = 0.001), recessive model (bb vs. Bb+BB: OR = 0.70, 95% CI = 0.56, 0.88; P_{heterogeneity} = 0.005) and dominant model (bb+Bb vs. BB: OR = 0.77, 95% CI = 0.61, 0.97; P_{heterogeneity} = 0.010), especially in studies based on Asian population. Sub-group analyses also revealed that there was a statistically decreased TB risk in “small” studies (<500 participants) and studies with P_HWE>0.5. Meta-regression and stratification analysis both showed that the ethnicity and sample size contributed to heterogeneity.

Conclusions

This meta-analysis suggests that VDR BsmI gene polymorphism is associated with a significant decreased TB risk, especially in Asian population.     

Allele-frequency determination of BsmI and FokI polymorphisms of the VDR gene by quantitative real-time PCR (QRT-PCR) in pooled genomic DNA samples

The vdr gene is a candidate for osteoporosis susceptibility, with conflicting results in association studies. We have designed and optimized an individual allele-specific and DNA pooling PCR-based methodology to quantitate BsmI and FokI polymorphisms of the vdr gene and studied single-nucleotide polymorphisms (SNPs) from pooled DNA samples. The allele frequency in DNA pooling experiments has been analyzed by kinetic PCR: quantitative real-time PCR (QRT-PCR). A Spanish cohort of 225 healthy postmenopausal women was studied. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DEXA) and quantitative ultrasound calcaneous densitometry. Allele-specific PCR amplification of BsmI and FokI genes showed full concordance with the PCR-RFLP approach. The prevalence of the three BsmI VDR genotypes was 19.1, 44.9 and 36.0% for BB, Bb and bb, respectively. In the case of the FokI locus, the prevalence of genotypes was 40.4, 48.0 and 11.6% for FF, Ff and ff, respectively. No positive correlation was found between polymorphism and BMD. The DNA pooling procedure was validated. No differences were found in allele frequencies and T-score data obtained using the high throughput DNA pooling approach, as compared to known individual frequencies. In our hands, this is a very useful approach to study quantitative (thus polygenic) traits like osteoporosis susceptibility.     

Vitamin D receptor levels in colorectal cancer. Possible role of BsmI polymorphism

A high expression of vitamin D receptor (VDR) in colorectal cancer (CRC) tumoral tissue has been related to a good prognosis and it has been proposed that it could be a good biological marker of CRC progression. Nevertheless, there are no previous studies that compare the VDR expression in tumoral towards normal tissue of the same CRC patient in relation to VDR BsmI genotype. We collected normal and tumoral tissue samples, as well as blood samples, from CRC patients (n=170) and controls (n=122). VDR genotyping was performed and BsmI homozygous patients were selected (CRC=50, Cont=32). VDR mRNA and protein levels were analyzed. We also measured 25-Hydroxyvitamin D serum levels. We found no differences in the polymorphism distribution in tumoral versus normal tissue (control: BB=15.7%, bb=41.3%, Bb=43%; CRC: BB=14.2%, bb=41.9%, Bb=43.9%). Furthermore, VDR levels decreased in colonic cancer tissue (mean: 3.03) versus normal mucosa (11.62) from the same patient (p<0.001), but this decrease was similar in both genotypes. There were differences in 25-Hydroxyvitamin D(3) levels between the CRC and the control group (CRC=8.65 ng/ml, Cont=18.15 ng/ml). In conclusion, we found a decrease in VDR levels in tumoral compared with normal mucosa from the same patient. This difference is independent of the BsmI polymorphism.     

Association of vitamin D receptor gene polymorphism with the urine calcium level in nephrolithiasis patients

Abstract

Association of vitamin D receptor (VDR) gene polymorphism with the urine calcium level in nephrolithiasis patients from the published reports are still conflicting. This study was conducted to evaluate the relationship between VDR BsmI (rs1544410), Fok1 (rs2228570), TaqI (rs731236) and ApaI (rs7975232) gene polymorphism and urine calcium level in nephrolithiasis patients using meta-analysis method. The association studies were identified from PubMed, and Cochrane Library on 1 April 2014, and eligible investigations were included and synthesized using meta-analysis method. Four reports were recruited into this meta-analysis for the association of VDR BsmI, Fok1, TaqI and ApaI gene polymorphism with urine calcium level in nephrolithiasis patients. In this meta-analysis, VDR BsmI B allele and BB genotype, Fok1 f allele and ff genotype, TaqI, and ApaI gene polymorphism were not associated with urine calcium level in nephrolithiasis patients. However, the BsmI bb genotype and Fok1 FF genotype were associated with the urine calcium level in nephrolithiasis patients. In conclusion, VDR BsmI bb genotype and Fok1 FF genotype were associated with the urine calcium level in nephrolithiasis patients. However, more studies should be conducted to confirm it.     

A meta-analysis of association of vitamin D receptor BsmI gene polymorphism with the risk of type 1 diabetes mellitus

Abstract

Association between vitamin D receptor (VDR) BsmI (rs1544410) gene polymorphism and the risk of type 1 diabetes mellitus (T1DM) from the published reports are still conflicting. This study was conducted to evaluate the relationship between VDR BsmI gene polymorphism and the risk of T1DM using meta-analysis method. The association studies were identified from PubMed, and Cochrane Library on 1 December 2013, and eligible investigations were included and synthesized using meta-analysis method. Twenty-three reports were recruited into this meta-analysis for the association of VDR BsmI gene polymorphism with T1DM susceptibility. In overall populations, bb genotype was associated with T1DM, but the B allele and BB genotype were not. In Asians and Latino population, B allele and bb genotype were associated with TIDM risk, but BB genotype was not. In Caucasians, VDR BsmI gene polymorphism was not associated with the T1DM risk. In Africans, B allele and BB genotype were associated with T1DM risk, but the bb genotype was not. However, the sample size for Latino population and Africans was small. In conclusion, VDR BsmI B allele, bb genotype was associated with T1DM risk in Asians, and bb genotype was associated with T1DM risk in overall populations. However, more studies should be conducted to confirm it.     

Association between Vitamin D receptor polymorphisms and the rate of bone loss in elderly women-importance of adjusting for dietary and lifestyle factors

The association between the restriction length polymorphisms of the Vitamin D receptor (VDR) gene and the bone mineral density (BMD) or the rate of bone loss is still under debate. In a longitudinal study of untreated postmenopausal elderly women, we evaluated the relationship between the VDR gene polymorphisms (BsmI, TaqI, ApaI, and FokI) and the rate of bone loss over a 3-year period. We also examined the effect of adjustments for dietary and lifestyle factors on these associations. Before adjustments, the rate of femoral neck bone loss was - 3.76 +/- 1.58% in women with BB genotype and 0.45 +/- 0.65% in women with bb genotype, which was not significantly different. Upon adjustment for dietary and lifestyle factors, statistically significant (P = 0.03) bone loss was observed at femoral neck in women with BB genotype (- 3.66 +/- 2.44%) compared to that of bb genotype (2.39 +/- 1.32%). Similar results were observed with TaqI genotypes. The rates of bone loss at other skeletal sites were not different between VDR genotypes defined by BsmI and TaqI. VDR gene polymorphisms defined by ApaI and FokI were not related to the rate of bone loss.     

Vitamin D Receptor Gene Polymorphisms on the Risk of Tuberculosis,a Meta-Analysis of 29 Case-Control Studies

The relationship of four potentially functional polymorphisms of the vitamin D receptor (VDR) gene, ApaI, BsmI, FokI and TaqI , with tuberculosis susceptibility were considered. The aim of this meta-analysis was to explore the association between the four polymorphisms and tuberculosis risk in different ethnic backgrounds. Eligible case-control studies that were catalogued before April 1^st 2013 were enrolled, and the heterogeneity between the studies was evaluated using a χ² based Q-test. Fixed and random effect models were built to evaluate the association of the four polymorphisms with the risk of tuberculosis, and the association between the four polymorphisms and tuberculosis was expressed as the odds ratio (OR) and 95% confidence interval (CI). Finally, twenty nine qualified studies were enrolled for this meta-analysis that included 6179 tuberculosis cases and 6585 healthy controls. The variant homozygote genotype of the FokI polymorphism was associated with a significantly increased risk of tuberculosis when compared to the heterozygote and wild type homozygote genotypes in the Chinese population (ff vs. Ff+FF: OR_recessive=1.97, 95%CI: 1.32-2.93, P _bonferroni=0.0032; heterogeneity test: χ²=0.24, P=0.62). For European subjects, the homozygote and heterozygote genotypes of the BsmI polymorphism were associated with a significantly decreased risk of tuberculosis when compared to the wild type homozygote (bb+Bb vs. BB: OR_dominant=0.41, 95%CI, 0.22-0.76, P _bonferroni=0.02; heterogeneity test: χ²=2.59, P=0.11). Based on the above results, we conclude that variants of the VDR gene that are homozygous for the FokI polymorphism might be more susceptible to tuberculosis in Chinese. Furthermore, larger sample studies are warranted to confirm the protective effects of BsmI variants on tuberculosis in the Europeans.     

Association analysis of vitamin D receptor gene polymorphisms with bone mineral density in young women with Graves' disease

Graves' (GD) hyperthyroidism induces accelerated bone turnover that leads to decreased bone mineral density (BMD). The role of the VDR gene in predisposition to primary osteoporosis has been recognized. Recent studies show associations between the VDR gene polymorphisms and susceptibility to autoimmune diseases. Here we analyzed if VDR gene polymorphisms: BsmI, ApaI, TaqI, and FokI may predispose women with Graves' hyperthyroidism to BMD reduction or to disease development. The subjects were 75 premenopausal female Polish patients with GD and 163 healthy women. The genotyping was performed by the use of the restriction fragment length polymorphism analysis (RFLP). We studied the association of the VDR polymorphisms and their haplotypes with patients' BMD and also SNPs and haplotypes association with Graves' disease. We found a strong linkage disequilibrium for the BsmI, ApaI, and TaqI polymorphims that formed three most frequent haplotypes in Graves' women: baT (47.9%), BAt (34.9%), and bAT (16.4%). We did not show statistically significant association of analyzed VDR polymorphisms or haplotypes with decreased bone mineral density in Graves' patients. However, the presence of F allele had a weak tendency to be associated with Graves' disease (with OR=1.93; 95% CI: 0.97-3.84; p=0.058). In conclusion: VDR gene polymorphisms do not predict the risk of decreased BMD in Polish women with Graves'. It may be speculated that the F allele carriers of the VDR-FokI polymorphism are predisposed to Graves' disease development.     

The BsmI vitamin D receptor gene polymorphism is associated with ulcerative colitis in Jewish Ashkenazi patients

Susceptibility to inflammatory bowel disease (IBD) has a strong genetic component. The vitamin D receptor (VDR) gene maps to a region on chromosome 12 shown to be associated with IBD in some studies. In this case-control study we determined the association between the BsmI VDR gene polymorphism and IBD in patients with Crohn's disease (CD) and ulcerative colits (UC). Three hundred seventy-nine Jewish Israeli patients with IBD, 228 with CD (129 Ashkenazi and 99 non-Ashkenazi), and 151 patients with UC (72 Ashkenazi, 79 non-Ashkenazi) were studied. The control group included 495 healthy blood donors (352 non-Ashkenazi and 143 Ashkenazi). All subjects were genotyped for the BsmI VDR gene polymorphism. The frequency of the BB genotype was higher in Ashkenazi patients with UC compared to Ashkenazi controls (0.21 vs. 0.11, p = 0.042, odds ratio 2.27, 95% confidence interval [CI] 1.06-4.9). There were no differences in the prevalence of the BB genotype or the B allele between ethnically matched patients with CD and UC. Nor were there differences in the BB genotype or B allele frequencies between CD patients and ethnically matched controls. The BsmI VDR gene polymorphism is associated with increased susceptibility to UC in Israeli Ashkenazi patients with UC.     

Association of vitamin D receptor gene polymorphism with the risk of renal cell carcinoma: a meta-analysis

Abstract

Relationship between vitamin D receptor (VDR) gene polymorphism and the risk of renal cell carcinoma from the published reports are still conflicting. This study was conducted to evaluate the relationship between VDR ApaI (rs7975232), BsmI (rs1544410), TaqI (rs731236), and Fok1 (rs2228570) gene polymorphism and the risk of renal cell carcinoma using meta-analysis method. The association studies were identified from PubMed, and Cochrane Library on 1 March 2014, and eligible investigations were included and synthesized using meta-analysis method. Five reports were recruited into this meta-analysis for the association of VDR gene polymorphism with renal cell carcinoma susceptibility. In this meta-analysis, the ApaI AA genotype, BsmI BB genotype, Fok1 f allele, and Fok1 FF genotype were associated with the risk of renal cell carcinoma in Asians. However, VDR ApaI, BsmI, TaqI, and Fok1 gene polymorphism were not associated with the risk of renal cell carcinoma in overall populations and in Caucasians. In conclusion, the ApaI AA genotype, BsmI BB genotype, Fok1 f allele, and Fok1 FF genotype were associated with the risk of renal cell carcinoma in Asians. However, more studies should be conducted to confirm it.     

Association of vitamin D receptor gene polymorphism with the risk of lung cancer: a meta-analysis

Abstract

Relationship between vitamin D receptor (VDR) gene polymorphism and the risk of lung cancer from the published reports are still conflicting. This study was conducted to evaluate the relationship between VDR TaqI (rs731236), BsmI (rs1544410) and ApaI (rs7975232) gene polymorphism and the risk of lung cancer using meta-analysis method. The association studies were identified from PubMed and Cochrane Library on 1 December 2013, and eligible investigations were included and synthesized using meta-analysis method. Six reports were recruited into this meta-analysis for the association of VDR gene polymorphism with lung cancer susceptibility. In the meta-analysis for ApaI gene polymorphism, AA genotype was associated with the risk of lung cancer in Asians. In the meta-analysis for BsmI gene polymorphism, B allele, BB genotype and bb genotype were associated with lung cancer in Asians, and B allele bb genotype were associated with lung cancer risk in overall populations; furthermore, bb genotype was associated with lung cancer risk in Caucasians. In the meta-analysis for TaqI gene polymorphism, t allele and TT genotype were associated with lung cancer in overall populations and in Caucasians. In conclusion, B allele bb genotype t allele and TT genotype were associated with lung cancer risk in overall populations. AA genotype, B allele, BB genotype and bb genotype were associated with the risk of lung cancer in Asians. Furthermore, bb genotype t allele and TT genotype was associated with lung cancer risk in Caucasians. However, more studies should be conducted to confirm it.     

Vitamin-D receptor genotype does not predict bone mineral density, bone turnover, and growth in prepubertal children.

We examined whether the polymorphism for BsmI restriction enzyme in the vitamin-D receptor (VDR) gene influenced radial (distal third) and lumbar (L2-L4) bone mineral density (BMD), phospho-calcium metabolism (calcium, phosphate, intact parathyroid hormone, 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D), biochemical markers of bone formation (osteocalcin and carboxy-terminal propeptide of type-I procollagen) and bone resorption (carboxy-terminal telopeptide of type-I collagen and urinary cross-linked N-telopeptides of type I collagen), insulin-like growth factor I and insulin-like growth factor-binding protein 3, and growth in 209 healthy prepubertal children (112 males and 97 females) aged 7.1-10.0 years. Genotype frequencies were BB 19%, Bb 46%, and bb 35% in the pooled group of children. Clinical findings, dietary calcium intake, calcium density, and physical activity rate were not different (p NS) among the VDR genotypes. Radial BMD, lumbar BMDarea and lumbar BMD adjusted for the apparent bone volume (BMDvolume), and all the biochemical parameters did not differ (p NS) in relation to the VDR genotype. In conclusion, our data show that polymorphism for BsmI restriction enzyme in the VDR gene is not associated with radial and lumbar BMD, parameters of phospho-calcium metabolism and bone turnover, growth hormone-dependent growth factors, and growth in prepubertal children.     

Vitamin D receptor polymorphisms in hypocalcemic vitamin D-resistant rickets carriers

BACKGROUND/AIMS: Hypocalcemic vitamin D-resistant rickets (HVDRR) is a rare autosomal recessive disorder characterized by severe rickets, hypocalcemia, secondary hyperparathyroidism, elevated levels of 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)], and occasionally, alopecia. In most cases, the disease is associated with mutations in the gene of the vitamin D receptor (VDR), the mediator of 1,25(OH)(2)D(3) action. The apparently healthy HVDRR heterozygotes express both normal and mutant VDR alleles, and they present higher levels of 1,25(OH)(2)D(3) than their respective controls. Because VDR function, except for the disease-causative mutations, might be influenced by the presence of certain polymorphisms, we investigated the distribution of four common VDR polymorphisms--BsmI, ApaI, TaqI and FokI--in HVDRR carriers compared with their respective controls. METHODS: Sixty-seven relatives of 2 HVDRR patients, all members of an extended Greek kindred, were included in the study. VDR allelic polymorphisms were assessed by restriction fragment length polymorphisms after specific polymerase chain reaction amplification. RESULTS: The distribution of genotypic and allelic frequencies differed between HVDRR carriers and their respective controls regarding BsmI and TaqI polymorphisms. The bb genotype and the T allele (presence of BsmI and absence of TaqI polymorphisms) were less frequent in the HVDRR carrier group than in the control group in a statistically significant manner (p = 0.029 and p = 0.025, respectively). CONCLUSIONS: Our findings showed that the apparently healthy HVDRR carriers present a different distribution of BsmI and TaqI VDR polymorphisms than their controls, suggesting that further investigation of the HVDRR carrier population may elucidate the implication of VDR alleles in VDR function and the vitamin D endocrine system.