Vitamin D Receptor Gene Variants Research Articles

EXPRESS: Effect of VDR and TLR2 gene variants on the clinical course of patients with COVID-19 disease.

The coronavirus disease 2019 (COVID-19) pandemic, which has caused a major global health crisis, primarily targets the upper and lower respiratory tract. But infected individuals may experience different clinical symptoms, ranging from asymptomatic to critical. The vitamin D receptor (VDR) and Toll-like receptor 2 (TLR2) polymorphisms play a role in the immune response. This study aimed to evaluate the effect of VDR Bsml (rs1544410) and TLR2 23bp indel variants on the clinical status of Turkish patients with COVID-19 disease. A total of 312 people, including 106 intensive care unit (ICU) patients, 103 symptomatic hospitalized patients, and 103 healthy controls, were included in the study. The VDR BsmI and TLR2 23bp indel were genotyped using polymerase chain reaction and/or restriction fragment length fraction (PCR-RFLP) methods. The VDR BsmI b/b genotype and b allele were higher in symptomatic patients compared to the healthy control group (p=0.035). The VDR BsmI B/B and B/b genotype distribution did not differ between ICU patients and both symptomatic patients and controls (p > 0.05). We found that B/B:B/b+b/b and B/B+B/b:b/b were significantly different in symptomatic patients compared to controls (p=0.033 and p=0.041, respectively). The VDR BsmI b/b genotype distribution was found to be lower in deceased patients than in living patients (p=0.023). There was no significant difference between the groups in terms of TLR2 23bp indel genotype and allele distribution (p > 0.05). Our study results suggest that the VDR BsmI b allele may have a role in COVID-19 patients with symptomatic findings. These data need to be repeated in different ethnic and larger sample groups.

Investigating the role of VDR gene variants in multiple sclerosis susceptibility: a case–control study in Egypt

BackgroundMultiple sclerosis (MS) is a chronic inflammatory disorder. Vitamin D has a major role in preventing inflammatory disorders as well as its role in the pathophysiology of MS. Vitamin D initiates its biological responses by binding to the nuclear vitamin D receptor (VDR). Several studies have been conducted over the last decade to investigate the relationship between VDR gene variants and the risk of MS, but the results have been inconsistent and inconclusive. The objective of this study is to investigate the association between the VDR gene variants (c.1025-49C>A) and (c.1056A>G) and MS susceptibility in a sample of the Egyptian population, and to shed light on its potential role in preventing inflammatory disorders and its impact on clinical outcomes and treatment using TaqMan Real-Time Polymerase Chain Reaction (PCR). This case-control study was conducted on 100 participants, categorized into two groups. The first group included 50 patients diagnosed with relapsing-remitting multiple sclerosis (RRMS) based on the Revised McDonald MS criteria, and the second group included 50 matched healthy participants. After collecting the blood samples, deoxyribonucleic acid (DNA) was extracted and detection of the VDR: c.1025-49C>A and VDR: c.1056A>G gene variants was done using TaqMan Real-Time PCR on all involved individuals.ResultsThe distribution of the genotypes and alleles of VDR gene variants (c.1025- 49C>A) and (c.1056A>G) did not differ significantly between MS patients and healthy participants (P>0.05 in both). ConclusionHere we show in this study that there was no association between the risk of MS and the VDR gene variants (c.1025-49C>A) and (c.1056A>G) in a group of the Egyptian population which may have impact on MS therapy and outcome.

Interplay between vitamin D status, vitamin D receptor gene variants and preeclampsia risk in Ghanaian women: A case-control study.

Preeclampsia (PE) is characterized by hypertension and proteinuria mostly after 20 weeks of gestation. It affects 2-8% of pregnancies worldwide, with detrimental consequences for both mother and foetus. Evidence, suggests that genetic factors, including vitamin D receptor (VDR) gene polymorphisms, could contribute to PE complexity. However, their role in the Ghanaian population remains underexplored. We assessed the interplay between Vitamin D, VDR gene variants and preeclampsia risk in Ghanaian women. This unmatched case-control study was conducted at Kumasi South Hospital, Ghana, from June to November 2022. A total of 162 participants consisting of 62 PE cases and 100 normotensive controls were enrolled. Clinical and obstetric data were collected. Blood samples were also collected for DNA extraction and vitamin D assay. Genotyping of VDR Fok1 and Bsm1 gene variants was performed using Polymerase Chain Reaction (PCR) and Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) analysis whereas Vitamin D levels were estimated using sandwich ELISA. Statistical analyses were computed with SPSS version 25 and GraphPad prism version 8.0. A p-value of < 0.05 was considered statistically significant. Vitamin D concentration were significantly lower in the PE group (p < 0.0001). Vitamin D deficiency (aOR = 3.311, 95% CI: 1.584-6.921, p = 0.0010) was significantly associated with a three-fold increase in preeclampsia risk, whilst VDR gene variants, particularly the "bb" genotype (cOR = 0.227, 95% CI: 0.055-0.944, p = 0.0410) was associated with reduced risk of PE. There was no association between the distribution of Fok1 genotypes and PE. This study highlights a significant association between vitamin D deficiency and an increased risk of PE among Ghanaian women. However, the VDR gene variant, "bb", genotype, for Bsm1 reduces the risk of PE.

Frequency of Healthy Control Genotype of VDR Gene Polymorphisms in the Saudi Population of the Ha'il Region: A Comparative Study with Worldwide Population.

Genetic polymorphisms in the vitamin D receptor (VDR) may influence the biological effects of vitamin D and increase a person's susceptibility to cancer. Previous studies have shown that different ethnic groups exhibit varying frequencies of the VDR gene variants TaqI, ApaI, FokI, and BsmI. However, the allelic distribution of these VDR polymorphisms in the Saudi population of Ha'il region is not sufficiently explored. In this study, efforts were made to ascertain the frequency of VDR polymorphisms in the Saudi population of Ha'il region, and then comparison was made for VDR polymorphism rates with other populations of the world. Allele and genotype frequencies of VDR TaqI, ApaI, BsmI and FokI gene was determined. The frequency distribution for the variant allele of VDR TaqI, ApaI, BsmI and FokI was found to be 70, 33, 50 and 25%, respectively. A significant frequency distribution was found for VDR-TaqI, ApaI and FokI variants in comparison with other populations of the world. Whereas, almost all of the studies dealing with VDR-FokI failed to show substantial difference while comparing with the data reported from the population of Ha'il region of Saudi Arabia. A significant pattern in the frequency of VDR gene variations have been found in the Saudi population of Ha'il region, which may be attributed to ethnic variance. The understanding of the worldwide distribution of VDR markers could help with high-risk screening of those who are exposed to environmental hazards and people of Ha'il region, who are predispose to cancer.

Association analysis between the VDR gene variants and type 2 diabetes.

Type 2 diabetes mellitus (T2DM) is recognized as a complex metabolic which has affected the lives of millions of people around the world. Vitamin D receptor (VDR) gene polymorphisms have been suggested to be a vital contributor to the development of T2DM. However, the association between VDR gene polymorphisms and T2DM remains controversial.We have investigated the association between two VDR gene polymorphisms (rs731236 and rs1544410) and T2DM in an Iranian population. A total of 148 T2DM patients and 100 normal controls were recruited in this study. We used polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis to perform genotyping. The results of the present research revealed that the frequency of the rs731236 C allele was significantly higher in T2DM patients than in normal controls (p = 0.044). The CC genotype of rs731236 was connected with an increased risk of T2DM (OR = 2.85, 95% CI = 1.06-7.69, p = 0.039). However, no significant difference in the frequency of the rs1544410 C allele between T2DM patients and normal controls was observed (p = 0.918). Our findings were suggestive of the rs731236 polymorphism of the VDR as a risk factor for developing T2DM in the Iranian population, while rs1544410 polymorphism may not be associated with T2DM susceptibility. Further research is needed to approve these findings in other populations and to clarify the underlying mechanisms involved in such an association. The online version contains supplementary material available at 10.1007/s40200-023-01323-0.

Associations of the &lt;i&gt;VDR&lt;/i&gt; gene with clinical manifestations and complications of cystic fibrosis

Cystic fibrosis (CF) is the most common severe autosomal recessive disease in the Caucasoid population caused by mutations in the CF transmembrane regulator (CFTR) gene. However, the course of the disease may be modulated by genetic factors other than the CFTR gene and may be pleiotropically influenced by VDR (Vitamin D Receptor) gene. The aim of the study was to search for associations between genetic variants (c.1206T&gt;C(A&gt;G), c.152T&gt;C, c.1174+283G&gt;A) of VDR gene and clinically significant manifestations of CF, complications, and responses to therapy. Methods. Patients with CF (n = 283) and healthy children (n = 333), who formed the control group, were examined. Calcidiol levels were tested in all subjects. Polymorphic variants of VDR gene (c.1206T&gt;C(A&gt;G), c.152T&gt;C, c.1174+283G&gt;A) were tested by polymerase chain reaction and restriction fragment length polymorphism analysis. Results. It was found that carriers of the TT genotype of the c.152T&gt;C FokI variant of VDR gene are 6.3 times more likely to develop meconium ileus (odds ratio – OR – 6.375; p = 0.011), 3.2 times more likely – respiratory failure (OR – 3.253; p = 0.079), 3.4 times more likely – chronic lung infection (CIL) caused by Pseudomonas aeruginosa (OR – 3.432; p = 0.026), and 4 times more likely – CIL caused by non-fermenting gram-negative bacteria (OR – 4.056; p = 0.009). Carriers of the CC genotype of the c.1206T&gt;C(A&gt;G) TaqI genetic variant use systemic corticosteroids more frequently (66% vs 7%) (OR – 0.034; p = 0.001). It was shown that the AA genotype of the BsmlI polymorphism (c.1174 + 283G&gt;A) is 4 times more likely to be detected in children with CF-associated liver diseases (OR – 4.300; p = 0.051). Conclusion. The contribution of all studied genetic variants c.1206T&gt;C(A&gt;G) TaqI, c.152T&gt;C FokI, BsmlI (c.1174+283G&gt;A) of the VDR gene to the clinical manifestations, complications and response to therapy in CF is described.

Vitamin D levels and &lt;i&gt;TaqI&lt;/i&gt;, &lt;i&gt;BsmI&lt;/i&gt; and &lt;i&gt;ApaI&lt;/i&gt; variants of the vitamin D receptor gene in coronary heart disease patients with disease debut at different ages

Introduction. Vitamin D deficiency may be a natural predictor of the onset of coronary heart disease (CHD) and myocardial infarction (MI) at a young age. The results of studies of the various variants association of the vitamin D receptor (VDR) gene with the risk of CHD are contradictory, which leads to the study of genetic variants of the VDR gene as predictors of the onset of the disease at the age of 45 years and younger in the Russian population. The objective was to determine the distribution of TaqI, BsmI and ApaI genotypes of the VDR gene variants and the level of vitamin D sufficiency in CHD patients with different age of onset of the disease and myocardial infarction, among residents of St. Petersburg. Methods and materials. The study included 410 CHD patients and 320 examined patients without CHD clinical signs of comparable age (p&gt;0.05). All patients with CHD underwent coronary angiography. Typing of VDR gene variants was carried out by polymerase chain reaction and subsequent restriction analysis. Determination of the level of 25(OH)D blood serum was carried out by enzyme immunoassay. Results. The level of 25(OH)D in the blood serum of CHD patients was lower than in the control group (15.61±0.52 ng/ml and 20.82±0.69 ng/ml respectively; p=0.001). Severe 25(OH)D deficiency was detected more often in CHD patients and was associated with an increased risk of CHD (23 % and 8 % respectively; p=0.001, OR=3.54 (1.88÷6.67)). The normal level of 25(OH)D sufficiency was more often detected in patients from the comparison group than in CHD patients, and was associated with a decrease of CHD risk (16 % and 4 % respectively; p=0.0002, OR=OR=0,21 (0,09÷0,48)). The presence of the aa genotype and the a allele (ApaI), the bb genotype and the b allele of the VDR gene (BsmI) is associated with an increased risk of CHD and the onset of the disease and MI at the age of 45 years and younger. Conclusions. Severe 25(OH)D deficiency is typical for CHD patients and was associated with an increased risk of CHD. The presence of the aa genotype and the a allele (ApaI), the bb genotype and the b allele of the VDR gene (BsmI) is associated with an increased risk of CHD and with the onset of the diseases and myocardial infarction at a young age. The TaqI variant of the VDR gene is not associated with the risk of CHD.

The severity of coronary artery defeat in coronary heart disease patients with different variants of the vitamin D receptor gene and the level of vitamin D sufficiency

Introduction. Vitamin D deficiency may be an independent predictor of coronary heart disease (CHD) and the severity of coronary atherosclerosis. The results of studies of the association of various polymorphisms of the vitamin D receptor (VDR) gene with the risk and severity of CHD are contradictory, which necessitates the study of genetic variants of the VDR gene and the characteristics of the clinical course of CHD in the Russian population.The objective was to determine the distribution of genotypes of TaqI, BsmI and ApaI of polymorphic variants of the VDR gene and the level of vitamin D sufficiency in CHD patients with varying severity of CHD, residents of St. Petersburg.Methods and materials. The study included 407 CHD patients and 318 patients without clinical signs of CHD of comparable age (p&gt;0.05). All CHD patients underwent coronary angiography. Typing of the VDR gene variants was performed by polymerase chain reaction and subsequent restriction analysis. Determination of the level of 25(OH)D blood serum was carried out by enzyme immunoassay.Results. Vitamin D deficiency was detected in 82 % of CHD patients, the content of 25(OH)D in blood serum was lower in CHD patients who had 2 or more myocardial infarctions (MI) than in those who had one MI (p=0.03). Vitamin D deficiency is associated with a 3.6-fold increased risk of multivessel disease (p=0.01). The presence of the aa genotype and the a allele (ApaI), the bb genotype and the b allele of the VDR gene (BsmI) is associated with an increased risk of CHD and the severity of atherosclerotic lesions of the coronary arteries.Conclusion. Vitamin D deficiency is typical for CHD patients and is associated with the severity of coronary atherosclerosis. The presence of aa genotype and a allele (ApaI polymorphism), bb genotype and b allele of the VDR gene (BsmI polymorphism) is associated with an increased risk of CHD and the severity of atherosclerotic lesions of the coronary arteries. TaqI polymorphism of the VDR gene is not associated with the risk of CHD.

Association Between Gene Polymorphisms of Inflammatory Cytokines and Vitamin D Receptor Gene with the Risk of Insulin Resistance and Dyslipidemia in Type 2 Diabetic Patients

The most common form of diabetes is Type 2 diabetes (T2D), and metabolic disease is the most prevalent. Inflammatory cytokines are involved in the pathogenesis of T2D and the presence of complications. The common problem is vitamin D deficiency, linked to an increased risk of obesity and metabolic dysfunction. Furthermore, vitamin D deficiency contributes to metabolic disorders; vitamin D receptor (VDR) gene polymorphisms play a role in these conditions. However, there are only a few data studies the relationships between them of small sample size and some selected polymorphisms of VDR. This opinion article investigates the association between genetic variants of inflammatory cytokines and VDR gene with the risk of insulin resistance (IR) and dyslipidemia in patients with T2D. The current project will identify the most significant risk factors for complications in T2D and clarify the causal relationship between vitamin D status and inflammatory markers with the increased risk of metabolic alterations in patients with T2D. Knowledge of these genetic variants might contribute to a better understanding of the role of inflammation and vitamin D deficiency in the etiology and progression of this disease and may lead to new strategies for prevention.

Vitamin D receptor gene polymorphisms in chronic kidney disease Egyptian children: effect on biochemical markers of bone mineral disorders.

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. The current study included 305 patients with CKD and 100 apparently healthy children. We measured the serum vitamin D (VD), para-thyroid 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. The TaqI AG &amp; 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 &amp; 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. Our study showed an association between VDR TaqI, BsmI polymorphisms and the susceptibility to CKD. The existence of VDR vari-ants affected the protein expression of VD, FGF-23 and PTH. The AGCA, AGCC and GGCA haplotypes were considered as protec-tive factors against the development of renal nephropathy in our population.

Vitamin D receptor gene polymorphisms (BsmI and FokI) and serum levels of 25-hydroxyvitamin D in Egyptian patients with type 2 diabetes and their association with atherosclerosis

Background/aim A large number of individuals with type 2 diabetes mellitus (T2DM) die owing to atherosclerotic cardiovascular diseases (CVD). The role of vitamin D deficiency and vitamin D receptor (VDR) gene polymorphisms in the development of T2DM-related CVD has yet to be established. We aimed to determine the association of 25(OH) vitamin D and VDR gene (BsmI and FokI) polymorphisms with T2DM and its accompanying atherosclerosis.Patients and methods This study enrolled 45 male patients with T2DM and manifested CVD who were admitted to the Department of Internal Medicine of Medical Research Institute Hospital, Alexandria University, Egypt, in addition to 45 healthy male volunteers. 25(OH) vitamin D was measured in all cases. Carotid intima-medial thickness was measured, in addition to analysis of VDR gene (BsmI and FokI) polymorphisms using PCR and restriction fragment length polymorphism for all studied participants.Results Significantly lower vitamin D levels were observed in the diabetic atherosclerotic group than controls. The minor allele f of the FokI polymorphism and the minor allele b of BsmI polymorphism were associated with a higher risk of coronary artery disease in patients with T2DM, with an odds ratio of 12.750 (P=0.002) and 6.122 (1.202–30.078), respectively. FF genotype had significantly lower levels of total cholesterol and low-density lipoprotein cholesterol than Ff and ff genotypes (P=0.01 and 0.04, respectively).Conclusion Presence of the f allele of FokI as well as the b allele of BsmI polymorphisms of the VDR gene could increase the risk of atherosclerosis in Egyptian patients with T2DM, through influencing lipid metabolism. Vitamin D deficiency might contribute to increased risk of atherosclerosis in T2DM independent of the variants of VDR gene.

VDR Polymorphisms in Autoimmune Connective Tissue Diseases: Focus on Italian Population.

Vitamin D is an important hormone involved in various physiologic processes, and its activity is linked to binding with vitamin D receptor (VDR). Genetic polymorphisms in the VDR gene could modulate the expression or function of the receptor and, consequently, alter the effects of vitamin D. Variants in VDR gene have been associated with susceptibility to many illnesses sensitive to vitamin D administration and to autoimmune disorders, but no data are available regarding autoimmune connective tissue diseases in Italian population. We analyzed three VDR polymorphisms in 695 Italian patients with autoimmune connective tissue diseases (308 with systemic lupus erythematosus (SLE), 195 with primary Sjogren's syndrome (pSS), and 192 with rheumatoid arthritis (RA)) and in 246 healthy controls with the aim to evaluate a possible association of VDR SNPs with susceptibility to these diseases in the Italian population. Genotyping of rs2228570, rs7975232, and rs731236 in VDR gene was performed by an allelic discrimination assay. A case/control association study and a genotype/phenotype correlation analysis have been performed. We observed a higher risk to develop SLE for rs2228570 TT genotype (P = 0.029, OR = 1.79). No association was observed between susceptibility to pSS or RA and this SNP, although this variant is significantly less present in RA patients producing autoantibodies. For rs7975232 SNP, we observed a significant association of the variant homozygous genotype with SLE (P = 0.009, OR = 1.82), pSS (P = 0.046, OR = 1.66), and RA (P = 0.028, OR = 1.75) susceptibility. Moreover, we reported associations of this genotype with clinical phenotypes of SLE and pSS. Lastly, the GG genotype of rs731236 was associated with a lower RA susceptibility (P = 0.045, OR = 0.55). Our results show that the explored VDR polymorphisms are significantly associated with autoimmune connective tissue disorders and support the hypothesis that the genetic variability of VDR gene may be involved in susceptibility to these diseases in Italian population.

Vitamin D receptor gene polymorphisms and risk of breast cancer in Iranian women

ObjectivesVitamin D deficiency is a driving force of common cancers like breast cancer. Vitamin D receptor (VDR) can play a tumor suppressor role by helping the precise function of vitamin D in cells such as modulation TGF-β signaling pathway. This study aimed to investigate the association of VDR gene variants and susceptibility to breast cancer in Iranian women. MethodsGenomic DNAs were isolated from blood samples of 161 women with breast cancer and 150 healthy women. After amplification of five positions of VDR gene, the prepared amplicons were digested with TaqI, ApaI, BsmI, Cdx2, and FokI restriction enzymes. ResultsSubsequently, the digested products were electrophoresed on the 1.5% agarose gel. Odds ratios (ORs) for breast cancer were calculated for genotypes and estimated haplotypes. Binary logistic regression analysis showed FokI (rs2228570), BsmI (rs1544410), and ApaI (rs7975232) polymorphisms had the significant distribution in patients than to the normal group. Analysis of linkage disequilibrium for all pairs of SNPs showed that D′-value between SNP TaqI and SNP BsmI was significantly (p ≤ 0.05). We observed that four major haplotypes of ApaI, BsmI, FokI, Cdx2, and TaqI SNPs significantly were in high frequency than predicted frequency. Among these four haplotypes, CGTAT haplotype was in a higher significant association than others with breast cancer risk (p-value = 0.0001). ConclusionOur results showed that FokI, BsmI, and ApaI of VDR polymorphisms associated with the risk of breast cancer in Iranian population.

Association analysis of pulmonary tuberculosis and vitamin D Receptor Gene Polymorphisms of Han population in Western China

ObjectiveTo investigate the associations between single nucleotide polymorphism (SNP) of vitamin D receptor (VDR) gene and tuberculosis (TB) infection risk. Methods597 newly diagnosed pulmonary tuberculosis (PTB) patients from the Han population in Western China were randomly selected while 901 healthy subjects were divided into control group from September 2015 to September 2018. In the case-control study, 21 SNPs within the VDR gene were genotyped. Use SPSS 19.0 statistical software, SNP statistical software (Plink) and Pub-med network database to analyze the correlation between VDR SNP and PTB susceptibility. ResultsThe 14 SNPs of VDR gene screened in the experiment were consistent with the frequency of PTB-related and minor alleles> 5% in HapMap Asian population. Three SNPs (rs58379944, rs11574012, rs12581281) were correlated with PTB by x2 analysis. The rs58379944, rs11574012 alleles “G" and rs12581281 alleles “A" in genotype analysis were susceptible to tuberculosis. In the genotype analysis, allele “G" of rs58379944 and rs11574012 and allele “A" of rs12581281 provided protection against PTB infection. Conclusionrs58379944, rs12581281 and rs11574012 allelic variants in VDR gene were found to be closely associated with PTB infection in the Han population in Western China. The protection it achieved may be one of the reasons for reducing the infection rate.

Vitamin D level, lipid profile, and vitamin D receptor and transporter gene variants in sickle cell disease patients from Kurdistan of Iraq.

IntroductionSickle cell disease (SCD) patients are susceptible to the development of vitamin D deficiency (VDD). Vitamin D through binding to vitamin D receptor (VDR) exerts its function and affects gene transcription in target tissues. VDR gene variants affect bone mineral density.MethodsIn a case‐control study, 101 SCD patients including 61 sickle cell anemia (SCA), 39 S/β‐thalassemia, and 1 HbS/HbD (SD) along with 110 healthy individuals from Kurdistan of Iraq were studied. The lipid profile, vitamin D level, FokI, and TaqI variants of VDR and group‐specific component (GC) were detected using the standard enzymatic method, the immunodiagnostic systems limited EIA kit and PCR‐RFLP methods, respectively.ResultsAround 93% and 82% of SCA and S/β‐thalassemia patients, respectively, had VDD compared to 83% of healthy individuals. Severe VDD (<10 ng/ml) was detected in 78.7% of patients with HbSS. Plasma levels of total cholesterol, HDL‐C, and LDL‐C in SCD patients were significantly lower compared to controls. Vitamin D levels were negatively correlated to TG and positively correlated to total cholesterol and HDL‐C. The frequencies of the C allele of FokI were 81.7% (p = 0.003), 80.3% (p = 0.034), and 84.6% (p = 0.011) in all SCD, SCA, and S/β‐thalassemia patients, respectively, compared to 69.1% in controls. However, no significant difference was detected comparing the frequencies of VDR TaqI and GC polymorphisms between SCD patients and controls.ConclusionIn the present study, we found hypocholesterolemia, high prevalence of VDR FokI C allele, and low vitamin D levels among children and adults with SCD from Kurdistan of Iraq.

Are Vitamin D Deficiency and VDR Gene Polymorphisms Associated With Higher Blood Pressure Defined by the 2017 ACC/AHA in Postmenopausal Women?

Postmenopausal status has been associated with an unfavorable phenotype tied to hormonal and metabolic changes, which collectively could contribute to an increased risk of cardiovascular disease. Vitamin D deficiency is frequent in postmenopausal women and may be linked to this phenotype and especially to an increased risk of developing hypertension. Vitamin D actions are modulated by the vitamin D receptor (VDR), and metabolic abnormalities have been associated with VDR gene variants in different populations. The aims of the present study were to assess the vitamin D levels, prevalence of vitamin D deficiency and genotypes of Fok-I, Bsm-I, Apa-I and Taq-I polymorphisms in the VDR gene and to determine whether vitamin D deficiency and VDR gene variants are associated with blood pressure levels and systemic arterial hypertension by the 2017 ACC/AHA definition in postmenopausal women. We conducted a cross-sectional study of biobanked blood samples from 339 postmenopausal women with no evidence of clinical disease. Blood pressure strata were defined according to the 2017 ACC/AHA cutoffs. Circulating 25(OH)D levels were considered deficient if <20 ng/mL. Genotype analysis was performed by RT-PCR with allelic discrimination assays. Mean serum total 25(OH)D levels were 22.99±8.54 ng/mL, and 40.1% of participants were deficient in vitamin D. Overall, 7.7% had elevated blood pressure, 36.6% had stage 1 and 37.8% had stage 2 hypertension. Mean total (p=0.014) and free 25(OH)D levels (p=0.029) were lower in women with stage 2 hypertension than in those with normal blood pressure. The CC+CT genotypes of Bsm-I and the AA+AG genotypes of Taq-I polymorphisms were more frequent in women with stage 2 hypertension (Bsm-I CC+CT: 85.8% vs. TT: 14.2%, p=0.045; Taq-I AA+AG: 91.3% vs. GG: 8.7%, p=0.021). A higher prevalence ratio of stage 2 hypertension was associated with age (PR 1.058; 95%CI 1.033-1.083; p<0.001), BMI (PR 1.046; 95%CI 1.025-1.068; p<0.001), vitamin D deficiency (PR 1.333; 95%CI 1.016-1.749; p=0.038) and Taq-I polymorphism (PR 1.764; 95%CI 1.030-3.019; p=0.039). Women with vitamin D deficiency and the AA+AG genotype of Taq-I polymorphism were 33% and 76% more likely to have stage 2 hypertension, respectively, but these analyses lost significance when adjusted for age and BMI. In conclusion, the present results suggest that vitamin D deficiency and Taq-I polymorphism are associated with stage 2 hypertension, depending on age and BMI, in postmenopausal women.

Vitamin D receptor gene polymorphism as a factor of early osteopenia formation in case of a combined course of osteoarthritis and obesity in young people

Objective: to reveal the prognostic-diagnostic significance of polymorphism of vitamin D receptor (VDR) gene G63980A, reference SNP (rs) 1544410, and possible prognostication of the risk of disorders appearance in the structural-functional state of the bone tissue in a combined course of osteoarthritis (OA) and obesity in young people.Methods: the study group included 96 patients at the age of (35.5 ± 0.9) years with OA and obesity, the control group were 96 practically healthy people of the same age and gender, the comparison group consisted of 18 patients with OA and the normal body mass.Obesity was classified after calculation of the body mass (Ketle) index. The functional state of the locomotor system was assessed by the WOMAC scale. The mineral density of the bone tissue was measured with bone densitometer Explorer QDR W (Hologic). Gene polymorphism was investigated in the human genome by the method of polymerase chain reaction. Odds ratio (OR) of the disease development was calculated.Results: severe radiological stages of joints were revealed 2.4 times more frequently in OA combined with obesity than in isolated OA. Osteoporosis was diagnosed in 59.4 % of patients from the study group versus 50 % in the comparison one. In the study group, patients with polymorphic variants of VDR gene, who had the B allele, predominated. The following risk factors for the development of OA were revealed: bone fractures in patients and their family members in the past history, genotype variation in VDR gene, age of the onset of disease under 30 and the radiological stage of OA.Conclusions: clinical-instrumental manifestations of the disease worsen in young patients with OA against a background of obesity. The same patients form osteoporotic disorders as early as during five years of the combined course of the above nosologies. Prognostically unfavourable factors are as follows: the BB variant of VDR gene, fractures in patients and their family members’ past history, manifestation of the disease under 30 years of age and the radiological stage of OA.

Unveiling molecular associations of polymorphic variants of VDR gene (FokI, BsmI and ApaI) in multiple myeloma patients of Indian population

Multiple myeloma (MM) is a plasma cell malignancy frequently accompanied with skeletal co-morbidity. Vitamin D (1,25(OH)2D) is an important mediator of skeletal homeostasis that mediates its effect by binding to vitamin D receptor (VDR), a steroid family receptor and modulates various downstream pathways. Multiple polymorphisms have been determined in VDR gene that witnessed significant association with cancer development and progression. Therefore, in this maiden study, we recruited 75 newly diagnosed MM patients and 75 control subjects. 25-hydroxy vitamin D (25(OH)D) levels were measured in all recruited study subjects. Further, PCR-RFLP was performed in DNA samples of recruited study subjects. Results demonstrated significantly decreased 25(OH)D levels in MM patients compared to controls. Additionally, decreased 25(OH)D levels in MM patients inversely associated with disease severity. Further, single nucleotide polymorphism (SNP) analysis of VDR gene showed significantly higher risk of MM disease development in Ff + ff, Aa + aa, and Bb + bb genotypes. Additionally, FokI f, ApaI a and BsmI b alleles were significantly associated with MM occurrence. In conclusion, this study provided initial evidences of association between 25(OH)D insufficiency, VDR gene polymorphism and MM development. Thus, we suggest that a study involving assessment of 25(OH)D levels and VDR gene polymorphism in large patients’ cohort might substantiate their role in MM development which would further provide impetus to give 25(OH)D supplementation along with conventional chemotherapeutic agents for myeloma treatment in future.

Association of vitamin D receptor gene polymorphisms with disc degeneration.

Numerous candidate genes and single-nucleotide polymorphisms (SNPs) have been identified in the background of lumbar disc degeneration (LDD). However, in most of these underpowered studies, definitions of LDD are inconsistent; moreover, many of the findings have not been replicated and are contradictory. Our aim was to characterize LDD by well-defined phenotypes and possible endophenotypes and analyse the association between these and candidate vitamin D receptor (VDR) gene polymorphisms on a large (N = 1426) dataset. Seven candidate VDR SNPs were genotyped. Individual association, haplotype and gene-gene interaction analyses were performed. All degenerative endophenotypes were significantly associated with one or more candidate VDR gene variants. Haplotype analyses confirmed the association between the 3'-end VDR variants (BsmI, ApaI, TaqI) and Modic changes as well as the relationship of 5'-end variants (Cdx2, A1012G) with endplate defects. We also found significant interactions between the 3'- and 5'-end regulatory regions and endplate defects. Based on our results, VDR and its gene variants are highly associated with specific degenerative LDD endophenotypes. Understanding relationships between phenotype and gene variants is crucial for describing the pathways leading to the multifactorial, polygenic degeneration process and LDD-related conditions. These slides can be retrieved under Electronic Supplementary Material.

Protective association of VDR gene polymorphisms and haplotypes with multiple sclerosis patients in Egyptian population

BackgroundHypovitaminosis D is one of the hazardous factors for multiple sclerosis (MS) and can be attested by expanding clinical studies. We aimed to study vitamin D receptor (VDR) gene polymorphisms: FokI, BsmI, ApaI, TaqI, and Tru9I genotype; frequency; haplotype structure; and linkage disequilibrium (LD) in MS Egyptian patients. The study was conducted on 50 MS patients and 50 healthy controls of matching age and sex. Alleles and genotype variants of VDR gene SNPs were analyzed by PCR using the restriction fragment length polymorphism (RFLP). Haplotype and linkage disequilibrium analysis based on the five genetic loci was studied on the detected genotypes.ResultsFrequency of FokI genotype (Ff+ff) was significantly higher in healthy controls (50%) compared to MS (28%) (P = 0.03), and “f” allele was significantly associated with the control group (OR = 0.42, CI = 0.26–0.85, P = 0.015). Frequency of ApaI genotype (Aa+aa) was significantly higher in MS (60%) (P = 0.002), and “a” allele was significantly associated with MS cases (OR = 2.47, CI = 1.25–4.88, P = 0.008). TaqI allelic distribution showed significant association of “t” allele with control group (OR = 0.55, CI = 0.31–0.98, P = 0.04). Statistically significant LD was detected between BsmI and ApaI in controls and MS (D' = 0.89 and P < 0.001, and D' = 0.52 and P < 0.001), respectively. Odd ratios of “fAt” and “BAt” were 0.2 (95% CI = 0.06–0.66) and 0.43 (95% CI = 0.19–0.97), respectively, suggesting that MS risk was 5 times and 2.3 times lesser, respectively, for haplotype carriers compared to non-carriers.ConclusionThe study findings suggest that VDR gene variants “f,” “A,” and “t” alleles as well as VDR gene haplotypes “BAt” and “fAt” may have a protective effect against MS disease in Egyptian population.