Gene Polymorphisms BsmI Research Articles

Association of vitamin D receptor BsmI gene polymorphism with risk of osteoporosis: a meta-analysis of 41 studies

Vitamin D receptor (VDR) BsmI gene polymorphism has been reported to be strongly associated with osteoporosis risk in some studies. However, the results from those studies are still conflicting. We performed a meta-analysis of studies relating the VDR BsmI gene polymorphism to the risk of osteoporosis. The search was performed in the databases of PubMed, Embase, Cochrane Library and CBM-disc (China Biological Medicine Database) as of October 1, 2011, and the eligible investigations were recruited for this meta-analysis. Forty-one investigations were identified for the meta-analysis of association between VDR BsmI gene polymorphism and osteoporosis risk. There lacked an association between VDR BsmI gene polymorphism and osteoporosis risk for overall populations, Caucasians and Asians (overall populations: B vs b: p = 0.65, BB vs (Bb + bb): p = 0.14, bb vs (BB + Bb): p = 0.86; Caucasians: B vs b: p = 0.65, BB vs (Bb + bb): p = 0.38, bb vs (BB + Bb): p = 0.83; Asians: B vs b: p = 0.87, BB vs (Bb + bb): p = 0.62, bb vs (BB + Bb): p = 0.66). In conclusion, VDR BsmI B/b gene polymorphism is not associated with the susceptibility of osteoporosis in overall populations, Caucasians, and Asians.

Vitamin D receptor gene polymorphisms and sex steroid secretion in girls with precocious pubarche in Southern Brazil: A pilot study.

Evidence suggests that precocious pubarche (PP) girls may have higher risk of developing polycystic ovary syndrome (PCOS) at later ages. Vitamin D receptor (VDR) gene polymorphisms have been implicated in the risk of diabetes and PCOS, but little is known about the role of VDR in PP. To assess the frequencies of VDR gene ApaI, TaqI, BsmI, and FokI polymorphisms and to determine whether these variants are associated with sex hormone concentrations in patients with PP and controls from southern Brazil. Blood was collected from 36 girls with PP and 197 controls for genotyping of BsmI and FokI polymorphisms using real-time PCR and of ApaI e TaqI polymorphisms using restriction fragment length polymorphism. Hormone levels were also determined. Genotype GG of the ApaI single nucleotide polymorphism (SNP) was more frequent in PP (30.6%) than in controls (16.2%) [odds ratio (OR): 2.269; confidence interval 95% (95%CI): 1.015-5.076; p=0.042]. This genotype was also associated with lower estradiol [35.30 (14.80-50.48) pg/ml vs 12.22 (6.49-23.69) pg/ml; p=0.025] and total testosterone levels (0.52 (0.39-0.84) ng/ml vs 0.20 (0.11-0.47) ng/ml; p=0.005) as compared with the TT + TG genotypes in girls with PP. The distribution of TaqI, BsmI, and Fokl SNP was similar in PP and controls, and no association was found between these polymorphisms and sex steroid levels. The ApaI SNP of the VDR gene was associated with PP in the studied population and may modulate ovarian steroid secretion in these girls.

Association of Vitamin D Receptor Gene Polymorphisms with Colon Cancer

In this study, we investigated the association of two vitamin D receptor (VDR) polymorphisms BsmI and TaqI with colon cancer in a Caucasian population. The VDR gene polymorphisms BsmI and TaqI were detected by polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP)-genotyping assays by using endonucleases BsmI and TaqI, and an agarose gel electrophoresis technique in a series of 43 colon cancer patients and 42 healthy controls. Allele frequencies and genotype distributions were found to be similar in both cases and controls. When homozygous carriers and heterozygotes were combined for each allele, alleles B and T were found to be more common in the control group (p=0.039, χ(2)=4.276, odds ratio [OR]=0.312, 95% confidence interval [CI]=0.100-0.973 and p=0.039, χ(2)=4.258, OR=0.254, 95% CI=0.064-1.000, respectively). When genotypes were analyzed as pairs, the Bb/TT variant was higher in the control group at a statistically high significance (p=0.001, χ(2)=11.854, OR=0.122, 95% CI=0.032-0.460). The alleles B and T and the genotype combination Bb/TT were found to be higher in the control group, and thus BsmI and TaqI polymorphisms of the VDR gene may be possible risk factors for colorectal carcinogenesis.

Vitamin D receptor gene BsmI polymorphism B allele, but not BB genotype, is associated with systemic lupus erythematosus in a Han Chinese population

The vitamin D receptor (VDR) gene is a candidate gene for susceptibility to autoimmune disorders. Association studies of VDR polymorphisms and risk of systemic lupus erythematosus (SLE) have often produced conflicting results in different ethnic backgrounds. The aim of this study is to test the association between VDR gene BsmI polymorphism and the genetic susceptibility to SLE in a Han Chinese population. Three hundred and thirty-seven patients with SLE and 239 healthy controls were genotyped for the VDR gene BsmI polymorphism (rs1544410) by polymerase chain reaction and restriction fragment length polymorphism analysis in this study, after which the relationship between BsmI polymorphisms and the mRNA expression of VDR, as well as clinical manifestations in patients with SLE, was evaluated. It was found that the frequency of B allele was significantly increased in SLE relative to the control group (χ(2) = 4.681, p = 0.031), although the distribution of VDR BsmI polymorphism genotype frequencies did not differ significantly between patients and controls (χ(2) = 4.098, p = 0.129). Moreover, VDR B allele was found to be associated with lupus nephritis (p = 0.027) and also with production of anti-nucleosome antibodies (p = 0.037). The mRNA of VDR was markedly down-regulated in patients with VDR B allele compared with that in patients without B allele (p = 0.016). Our results indicate a possible role of genetic factors (the VDR B allele) in influencing disease susceptibility in Han Chinese patients. Also, VDR B allele is associated with the development of nephritis and the down-regulation of VDR mRNA expression in SLE.

Vitamin D receptor gene polymorphism in children with urinary tract infection

It is known that small alterations leading to different vitamin D receptor (VDR) alleles affect resistance or susceptibility to infections. In this study, we examined VDR gene polymorphisms in urinary tract infections (UTI), which are common and an important cause of morbidity in children and subsequently of renal scar formation. We evaluated 92 patients diagnosed with UTI and 105 children without prior history of UTI as a control group. The VDR gene polymorphisms BsmI, FokI, ApaI, and TaqI were evaluated in patients and controls. BsmI polymorphism genotype distribution was similar between groups. There was a significant difference between groups for FokI (p =0 < 001); for the ff genotype, the risk of UTI was significantly increased (p < 0.01) ,at 3.94 times higher (odds ratio = 3.94; 95% confidence interval 1.71-9.09). ApaI polymorphism was significantly increased in the control group (p < 0.01) and evaluated as a protective factor. Comparing the TaqI genotype between groups, there was no statistically significant difference, but in both Tt and tt genotypes, there was minimal increased risk of UTI. The results of this study suggest that VDR gene polymorphisms can be important for susceptibility to UTI and renal scar formation. Association between VDR polymorphisms and UTI is in accordance with the understanding of how vitamin D modulates the immune response against infections.

Vitamin D receptor FokI and BsmI gene polymorphism and its association with grade and stage of renal cell carcinoma in North Indian population

Vitamin D exerts its activity through binding to the high-affinity nuclear vitamin D receptor (VDR), and majority of genetic studies have primarily focused on variation within this gene. Therefore, analysis of genetic variation in VDR genes may provide insight into the role of vitamin D in renal cell carcinoma (RCC) etiology in our study population. This study investigated whether VDR gene polymorphisms were associated with increased risk and prognosis of RCC in the North Indian population. Genotyping of two polymorphic sites (FokI and BsmI) in the VDR gene of 196 RCC cases and 250 healthy controls was performed via PCR-RFLP. The frequency of homozygous genotype FF was 31.6%, heterozygous Ff was 48.0%, and homozygous ff was 20.4% in cases, whereas in controls it was 45.6%, 39.2%, and 15.2%, respectively; thus, there was a significant difference between the two groups (p (Trend) = 0.011) in the univariate model. The frequencies of the BB, Bb, and bb genotypes were 25.5%, 44.9% and 29.6% in cases, respectively, while in controls it was 33.2%, 52.0% and 14.8%, respectively; thus, there was a significant difference between the two groups (p (Trend) = 0.001) in the univariate model. The two high-risk genotype ff of FokI and bb of BsmI of VDR showed a cumulative 1.87-fold increase in risk to RCC. Moreover, the FF genotype was associated with lower pathological stage and histological grade. Our results suggest that the FokI and BsmI genotypes of VDR gene may be implicated in the pathogenesis of RCC.

Vitamin D receptor gene polymorphisms in a group of postmenopausal Turkish women: association wıth bone mineral density

Objective To determine the frequency of the vitamin D receptor (VDR) gene polymorphisms BsmI, ApaI, TaqI and FokI and their associations with bone mineral density (BMD) in postmenopausal Turkish women.Design One hundred and thirty healthy postmenopausal women and 130 premenopausal healthy women acting as controls were included in the study. The BsmI, FokI, ApaI and TaqI polymorphisms in the VDR gene were studied by polymerase chain reaction–restriction fragment length polymorphism method. The BMD of the lumbar vertebrae and femur neck were measured by dual-energy X-ray absorptiometry. Comparisons between the groups were performed using the paired t-test and ANOVA. χ or contingency tables were used to analyze qualitative results.Results Genotypes BB, Bb and bb occurred in premenopausal women with frequencies of 16.92%, 50% and 33.08% and in postmenopausal women with frequencies of 16.92%, 56.15% and 26.92%, respectively. Genotypes FF, Ff, ff occurred in premenopausal women with frequencies of 47.69%, 42.31% and 10% and in postmenopausal women with frequencies of 50.77%, 42.31% and 6.92%, respectively. Genotypes AA, Aa, aa occurred in premenopausal women with frequencies of 23.85%, 56.15% and 20% and in postmenopausal women with frequencies of 26.15%, 46.15% and 27.70%, respectively. Genotypes TT, Tt and tt occurred in premenopausal women with frequencies of 37.69%, 45.38% and 16.92% and in postmenopausal women with frequencies of 39.23%, 45% and 15.38%, respectively. There was no difference in the frequencies of VDR gene polymorphisms between premenopausal and postmenopausal women. BMD measurements were not different between genotypes in premenopausal and postmenopausal women.Conclusions The VDR gene BsmI, FokI, ApaI and TaqI polymorphisms have no major influence on bone mineral density in our group of postmenopausal women.

Start codon FokI and intron 8 BsmI variants in the vitamin D receptor gene and susceptibility to colorectal cancer

Epidemiological evidence suggests the protective effect of vitamin D against colorectal cancer (CRC) and the polymorphisms in vitamin D receptor (VDR) gene may influence the development of CRC. In this study the possible association of VDR FokI and BsmI gene polymorphisms with CRC risk was examined. A total of 904 subjects, including 452 cases with CRC and 452 controls were enrolled in this study. All 904 subjects were genotyped for VDR FokI and BsmI gene polymorphisms by PCR-RFLP method. We observed no significant difference in genotype and allele frequencies between the cases with CRC and controls for the both FokI and BsmI polymorphisms either before or after adjustment for confounding factors including age, BMI, sex, and smoking status. Furthermore, no evidence for effect modification of the association VDR gene FokI and BsmI variants and CRC by BMI, sex, or tumor site was observed. In addition, there was no significant difference in genotype and allele frequencies between the normal weight (BMI <25 kg/m(2)) cases with CRC and overweight/obese (BMI ≥25 kg/m(2)) cases with CRC for the two SNPs. Our results do not lend support to the hypothesis that VDR gene FokI and BsmI polymorphisms are associated with the risk of CRC. However, further studies are required to confirm this finding.

BsmI polymorphism in the vitamin D receptor gene is associated with leg extensor muscle strength in elderly men

Sarcopenia is defined as a reduction in skeletal muscle mass, strength, and endurance observed with advancing age. Although Vitamin D receptor (VDR) polymorphism is reported to be associated with muscle mass and strength, evidence for this is limited and conflicting. In this study, we examined the association between the polymorphisms of VDR gene BsmI, TaqI and FokI and muscular mass and strength in elderly men. This is a cross-sectional study conducted in a university hospital. One hundred and twenty men over 65 years of age participated, all participants were active men living independently in Istanbul, who were followed as outpatients in geriatric polyclinics. Most common diagnoses were hypertension, hyperlipidemia, and mild to moderate osteoarthritis. Morbid obese patients were not included in the study. Genomic DNA was extracted from peripheral blood, and VDR genotypes were determined by the polymerase chain reaction. The peak torque of the knee flexors and extensors was measured on a Cybex 350 dynamometer. Body muscle mass was calculated by using bioelectric impedance analysis. The extensor strength of the knee was higher in BB homozygotic men than in the Bb/bb group. No significant association was found with TaqI and FokI haplotypes. There was no significant association between muscle mass and strength, or between muscle mass and VDR genotype. Our data suggest that VDR gene BsmI polymorphism is associated with muscular strength in elderly men.

Lack of association of vitamin D receptor gene BsmI polymorphisms in patients with systemic lupus erythematosus

Several data link vitamin D to many autoimmune diseases. Association between vitamin D receptor (VDR) gene BsmI polymorphisms and systemic lupus erythematosus has been reported. In this study, we examine whether the VDR gene BsmI polymorphisms are markers for susceptibility to or severity of SLE. This study incorporated 60 patients with SLE living in northeastern Iran. Three genotypes, BB, Bb and bb, were detected based on polymerase chain reaction-restriction fragment length polymorphism (PCR/RFLP). The distribution of VDR genotyping in patients with SLE was 23.3% for BB, 60% for Bb and 16.7% for bb and in the control group was 33.3% for BB, 46.7% for Bb and 20% for bb (P = 0.334). No association of VDR gene BsmI polymorphisms with SLE disease activity index (SLEDAI), SLE damage score and major organ involvement was detected. The result of this study did not show any association between VDR gene BsmI polymorphisms and SLE.

The vitamin D receptor gene BsmI polymorphism is not associated with anthropometric and biochemical parameters describing metabolic syndrome in postmenopausal women

Aim. Vitamin D could have a direct effect on adipocyte differentiation and metabolism and might be involved in glucose regulation of insulin secretion. In recent years several polymorphisms in the gene encoding the vitamin D receptor (VDR), which are potent to alter the activity of VDR protein, have been described. The present study aimed to investigate the prevalence of the VDR BsmI polymorphism and its association with anthropometric and biochemical features of metabolic syndrome in postmenopausal women.Materials and methods. We studied 351 randomly selected healthy postmenopausal women, with mean age of 55.43 ± 2.75 years and mean body mass index (BMI) of 27.5 ± 4.78 kg/m2, to evaluate the frequency of BsmI polymorphism (by restriction fragment length polymorphism–polymerase chain reaction) in the VDR gene and to find out whether there is an association between this polymorphism and BMI, total fat volume and visceral fat (as determined by total body dual-energy X-ray absorptiometry), blood pressure, lipid profile (total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, triglycerides) glucose and fasting insulin in the whole group, as well as subgroups of obese and non-obese women.Results. The prevalence of BsmI genotypes in the study group was 51.0% Bb, 37.3% bb and 11.7% BB. Genotype distribution did not differ from that expected under Hardy–Weinberg equilibrium conditions (χ2 = 2.95, p = 0.22). Apart from LDL-C levels (F = 3.46, p = 0.032), there were no significant differences in anthropometric or metabolic parameters between genotypes.Conclusions. The BsmI polymorphism in the VDR gene does not seem to predispose to obesity and insulin resistance, but the BB genotype is connected with an unfavorable lipid profile.

Evidence for association between vitamin D receptor BsmI polymorphism and type 1 diabetes in Japanese

Type 1 diabetes is considered to be T-helper 1 (Th1) type autoimmune disease. Because the vitamin D receptor is expressed on CD4 + T cells and is known to affect cytokine responses, several groups have investigated the association between the vitamin D receptor gene BsmI polymorphism and type 1 diabetes. However, this issue is still controversial; therefore, we examined this gene polymorphism in a large number of type 1 diabetic patients as a multi-center collaborative study in Japan. A total of 1373 subjects, including 774 cases and 599 control subjects of Japanese origin, were studied. The frequency of carriers of the BB genotype in type 1 diabetic patients was significantly higher than that in controls ( p < 0.01, odds ratio 3.65). Moreover, IFN-γ production upon anti-CD3 stimulation in the BB genotype group was significantly higher than that in the Bb and bb genotype groups ( p < 0.05), suggesting that the polyclonal T cell response in BB genotype patients is Th1 dominant. Based upon these results, we propose that it may be worthwhile to focus on subjects with the BB genotype of this gene polymorphism as having high risk for type 1 diabetes.

Vitamin D receptor gene BsmI and TaqI polymorphisms and fracture risk: A meta-analysis

Introduction Fracture is the major clinical outcome of osteoporosis. The vitamin D receptor (VDR) gene is thought to be a candidate gene for osteoporosis. Many genetic studies have suggested an association of VDR polymorphisms and osteoporosis, but evidence remains conflicting. Materials and Methods We searched published studies from 1996 to September 2005 through PubMed and evaluated the genetic effect of the BsmI and TaqI polymorphism of VDR on fracture risk in a meta-analysis. Thirteen studies with a total of 20 eligible comparisons (1632 fracture cases and 5203 controls) were analyzed with fixed and random effects models. Result No evidence of relationship between the VDR BsmI or TaqI polymorphism and fracture risk was observed with any genetic model. The odds ratio (95% confidence interval) of b-allele versus B-allele was 0.98 (0.86–1.12) with random effects calculations. There was significant between-study heterogeneity. Small studies did not differ significantly from larger ones. Conclusion No relationship of the VDR BsmI or TaqI polymorphism and fracture risk was found in the meta-analysis of published data.

Vitamin D receptor gene polymorphism in rheumatoid arthritis and associated osteoporosis

Rheumatoid arthritis (RA) is commonly associated with decreased bone mineral density (BMD) due to numerous factors. BsmI polymorphism of the vitamin D receptor (VDR) gene has been implicated in the pathogenesis of osteoporosis. Vitamin D has several immunomodulatory effects and thus may play a role in the course of arthritis. However, little data is available on the possible relationship between RA and VDR gene polymorphisms. In this study, the frequency of BsmI polymorphism genotypes were compared with that found in other countries. In this study, 64 RA patients and 40 healthy controls were tested for VDR gene BsmI polymorphism genotypes. Frequencies of B and b alleles were associated with markers of bone metabolism and RA. Among control subjects, the frequency of the BB genotype is relatively high (27.5%). In RA with secondary osteopenia/osteoporosis the BB genotype was more rare, the bb was more common than in control subjects. Markers of bone metabolism were associated with the B allele. RA patients carrying the B allele had lower BMD and increased bone loss over 1 year. The B allele was also correlated with increased osteoclast and osteoblast function, as determined by the assessment of biochemical markers of bone metabolism. Rheumatoid factor titer, which is an independent marker for disease progression in RA, was higher in bb patients. Our data suggest, that the imbalance in B and b allele expression may be involved in the pathogenesis of RA-associated osteoporosis. The possible involvement of vitamin D and VDR gene polymorphisms in the development and progression of RA needs further elucidation.

Vitamin D receptor gene BsmI polymorphisms in Thai patients with systemic lupus erythematosus

The immunomodulatory role of 1,25-dihydroxyvitamin D3 is well known. An association between vitamin D receptor (VDR) gene BsmI polymorphisms and systemic lupus erythematosus (SLE) has been reported. To examine the characteristics of VDR gene BsmI polymorphisms in patients with SLE and the relationship of polymorphisms to the susceptibility and clinical manifestations of SLE, VDR genotypings of 101 Thai patients with SLE and 194 healthy controls were performed based on polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The relationship between VDR gene BsmI polymorphisms and clinical manifestations of SLE was evaluated. The distribution of VDR genotyping in patients with SLE was 1.9% for BB (non-excisable allele homozygote), 21.78% for Bb (heterozygote), and 76.23% for bb (excisable allele homozygote). The distribution of VDR genotyping in the control group was 1.03% for BB, 15.98% for Bb, and 82.99% for bb. There was no statistically significant difference between the two groups (p = 0.357). The allelic distribution of B and b was similar within the groups (p = 0.173). The relationship between VDR genotype and clinical manifestation or laboratory profiles of SLE also cannot be statistically demonstrated. In conclusion, we cannot verify any association between VDR gene BsmI polymorphism and SLE. A larger study examining other VDR gene polymorphisms is proposed.

101Vitamin D receptor gene BsmI and TaqI polymorphisms in Turkish patients with urinary tract stones

101Vitamin D receptor gene BsmI and TaqI polymorphisms in Turkish patients with urinary tract stones

Association of Vitamin D Receptor Gene Polymorphism and Parkinson's Disease in Koreans

1α,25-dihydroxyvitamin D3 (1,25(OH)2D3), which is the biologically active form of vitamin D, has anti-inflammatory effects and can prevent experimental Parkinson's disease (PD). 1,25(OH)2D3 exerts most of its actions only after it binds to its specific nuclear receptors. Eighty-five Korean patients with PD and 231 unrelated healthy individuals were evaluated to determine if vitamin D receptor gene (VDRG) BsmI polymorphisms were markers for the susceptibility to PD in Korean patients. Each polymorphism was detected using polymerase chain reaction (PCR)-based restriction analysis. In addition, the relationship between the BsmI polymorphisms and the clinical manifestations of PD was evaluated. Overexpression of the b allele (91.2 vs. 85.7%; p=0.069) and homozygote bb (84.7 vs. 72.7%; p=0.043) was found in the PD patients compared with the controls. These results show for the first time an association between PD and a VDRG polymorphism, which might be involved in the pathogenesis of PD, or in the linkage disequilibrium of the VDRG to another pathogenic gene locus.

Vitamin D receptor gene polymorphism BsmI is not associated with the prevalence and severity of CAD in a large-scale angiographic cohort of 3441 patients.

Recent studies found a relationship between Vitamin D and atherosclerosis. A common genetic polymorphism of the Vitamin D receptor (VDR) has been associated with coronary artery disease (CAD) in small study populations. To assess its influence on the prevalence and severity of CAD we studied a large-scale population. A total of 3441 consecutive patients were referred for diagnostic coronary angiography. The BsmI Vitamin D receptor polymorphism was analyzed by polymerase chain reaction. Angiography was used to define phenotypes with clear coronary arteries (n = 775), coronary sclerosis (diameter stenosis < 50%; n = 579), CAD (diameter stenosis > 50% in at least one vessel; n = 1524). Patients with CAD at a young age (females aged less than 65 years, males aged less than 55 years; n = 563) were specially defined as premature CAD. The risk profile of traditional cardiovascular risk factors was obtained for every patient. The genotype frequencies of the VDR BsmI polymorphism did not differ between all four phenotypes (P = 0.756). The allele frequencies for the B allele were 0.43 vs. 0.44 vs. 0.42 vs. 0.45 in the four phenotypic groups (P = 0.827). All traditional cardiovascular risk factors (hypercholesterolaemia, smoking, hypertension, diabetes mellitus, severe obesity, male gender) were significantly (P < 0.001) associated with the angiographic phenotype. The VDR gene variant BsmI was not associated with prevalence and severity of CAD in a large-scale cohort phenotyped by angiography.

Vitamin D receptor gene BsmI-polymorphism in Finnish premenopausal and postmenopausal women: its association with bone mineral density, markers of bone turnover, and intestinal calcium absorption, with adjustment for lifestyle factors.

Bone mineral density (BMD) is regulated by genetic and environmental factors. Sixty percent to 80% of bone mass is suggested to be under polygenetic control, but the role of individual genes seems to be modest. Several studies have indicated that the vitamin D receptor ( VDR) gene has a role in the regulation of BMD and bone metabolism, but the results are very controversial. We studied the associations between BsmI-polymorphism of the VDR gene and BMD and bone metabolism in 24 premenopausal (aged 22-45 years) and 69 postmenopausal (aged 48-65 years) Finnish women. The BMD of the lumbar spine and femoral neck and bone turnover markers were measured, and the intestinal calcium absorption was investigated, using a method based on the absorption of non-radioactive strontium. The genotype distribution was 16%, BB; 34.5%, Bb; and 49.5%, bb, which differs from the genotype distribution found in other Caucasian populations, but is similar to earlier Finnish reports. The winter value of 25-hydroxyvitamin-D (25-OH-D) was highest for the BB genotype in both age groups (analysis of covariance [ANCOVA]; premenopausal women P = 0.5, postmenopausal women P = 0.03, and for the groups combined P = 0.02). Lumbar spine BMD and intestinal strontium absorption were highest for the BB genotype in both age groups, but these results were nonsignificant. The markers of bone metabolism did not differ significantly between the VDR genotypes. The BB genotype had the best vitamin D status, which could explain the differences in calcium absorption between the genotypes. However, the conclusions of our study are limited because of the small number of subjects.

The impact of vitamin D receptor genotype on the management of anemia in hemodialysis patients

Background: Both in vitro and in vivo studies have shown that calcitriol, the active form of vitamin D, is involved in hematopoiesis. We hypothesized that the vitamin D receptor (VDR) genotype, which may differentiate response to endogenous or exogenous active vitamin D, has a role in the management of anemia in hemodialysis (HD) patients. Methods: The VDR BsmI gene polymorphism was determined in 91 HD patients and 85 healthy controls. In addition to well-known factors responsible for both anemia and inadequate response to erythropoietin (EPO), we examined the contribution of the VDR genotype to hematocrit (Hct), hemoglobin (Hb) level, total weekly dose of EPO, and EPO-Hb ratio as an index of patient EPO need. Results: Genotype distributions for the VDR gene were under the Hardy-Weinberg equilibrium and similar in patients and controls (genotypes BB, Bb, and bb: 22.0%, 38.5%, and 39.5% in patients versus 24.7%, 48.2%, and 27.1% in controls). There were statistically significant differences in Hct, Hb level, EPO dose, and EPO-Hb ratio in patients with the three BsmI genotypes, whereas the other parameters were the same. Comparison of patients with an Hb level less than versus greater than 11 g/dL showed that the former patients had lower albumin levels (P = 0.001), higher C-reactive protein levels (P = 0.014), and a greater frequency of BB genotype (P < 0.001). Similarly, comparison of patients with an EPO-Hb ratio in the highest quartile versus those in the lowest quartile showed that the former patients had lower albumin and transferrin levels (P = 0.013 for both) and greater frequencies of BB genotype (P = 0.016). In logistic regression analysis, both BB genotype and low serum albumin level were found to be the only independent predictors for an Hb level less than 11 g/dL (P < 0.001 and P = 0.046, respectively). Both parameters also predicted being in the highest quartile of EPO-Hb ratio (P = 0.004 for both). Conclusion: The VDR BsmI gene polymorphism may predict both Hb level and EPO need in HD patients. However, because the underlying mechanisms have not been clarified in the present study, further research on this issue is needed. © 2002 by the National Kidney Foundation, Inc.