BsmI Polymorphisms Research Articles

Lack of Association Between BsmI and FokI Polymorphisms of the VDR Gene and Sporadic Colorectal Cancer in a Romanian Cohort-A Preliminary Study.

Colorectal cancer (CRC) is a major public health problem worldwide, currently ranking third in cancer incidence and second in mortality. Multiple genes and environmental factors have been involved in the complex and multifactorial process of CRC carcinogenesis. VDR is an intracellular hormone receptor expressed in both normal epithelial and cancer colon cells at various levels. Several VDR gene polymorphisms, including FokI and BsmI, have been evaluated for their possible association with CRC susceptibility. The aim of our study was to investigate these two SNPs for the first time in Romanian CRC patients. FokI (rs228570 C>T) and BsmI (rs1544410 A>G) were genotyped by real-time polymerase chain reaction (RT-PCR) in 384-well plates using specific TaqMan predesigned probes on a ViiA™ 7 RT-PCR System. A total of 441 subjects (166 CRC patients and 275 healthy controls) were included. No statistically significant difference was observed between CRC patients and controls when we compared the wild-type genotype with heterozygous and mutant genotypes for both FokI (OR 0.85, 95% CI: 0.56-1.28; OR 0.95, 95% CI: 0.51-1.79, respectively) and BsmI (OR 0.97, 95% CI: 0.63-1.49; OR 1.10, 95% CI: 0.65-1.87, respectively) or in the dominant and recessive models. Also, we compared allele frequencies, and no correlation was found. Moreover, the association between these SNPs and the tumor site, TNM stage, and histological type was examined separately, and there was no statistically significant difference. In conclusion, our study did not show any association between FokI and BsmI SNPs and CRC susceptibility in a Romanian population. Further studies including a larger number of samples are needed to improve our knowledge regarding the influence of VDR polymorphism on CRC susceptibility.

Evaluation relationship between VDR gene and clinical and inflammatory factors in patients with RRMS.

Adipocyte levels including leptin and FABS-4 levels, adiponectin, obesity, and vitamin D can be related to the occurrence and exacerbation of MS disease. This research aimed at determining the relationship between VDR gene changes and clinical and inflammatory factors in patients with relapsing-remitting multiple sclerosis (RRMS). This case/control study was conducted based on the ethical principles of Helsinki. RRMS disease was confirmed based on history, clinical signs, radiological signs, and neurologist's diagnosis. The research population consisted of healthy people and patients with RRMS referring to Hazrat Rasool Akram Hospital between 2021 and 2023 who met the criteria for entering the research. FokI polymorphism is associated with a substantial increase in risk, with an odds ratio of 7.28, for those with the FF genotype who have RRMS compared to healthy individuals (OR=7.28: 95% CI; 1.86, 28.41). The presence of FokI polymorphism significantly raises the likelihood of developing RRMS in persons with the FF genotype compared to healthy individuals, with an odds ratio of 28.7. RRMS patients with genotypes did not exhibit a significant increase in risk compared to controls for FokI, ApaI, TaqI, and BsmI polymorphisms. None of the studied polymorphisms revealed a significant risk in obese patients with different genotypes compared to the obese people. Further research, including more cases, is needed to avoid results that could be inflated by small samples or low frequencies of minor alleles.

Association between vitamin D receptor gene polymorphisms and susceptibility to tuberculosis: a systematic review and meta-analysis.

Tuberculosis (TB) is the leading cause of mortality worldwide. Previous studies have reported that TB susceptibility can be caused by vitamin D deficiency, which is affected by polymorphisms in the vitamin D receptor (VDR) gene. However, these results have been inconsistent. Therefore, we performed a meta-analysis to investigate the association between VDR polymorphisms and TB susceptibility. We systematically searched for relevant literature in PubMed, Embase, and Medline databases through December 31st, 2022. Inclusion and exclusion criteria were made to ensure that HIV-negative population is the targeted subjects. The pooled odds ratio (OR) and 95% confidence interval (CI) were then used to assess the strength of the association, and the quality of the included articles was evaluated using the Newcastle-Ottawa Scale. Potential sources of heterogeneity were evaluated based on subgroup and meta-regression analyses. In our meta-analysis, we found that the FokI polymorphism in the VDR gene was associated with increased TB susceptibility in the allele and recessive genotype models (OR f vs. F = 1.235, 95%CI: 1.035-1.475; OR ff vs. Ff + FF = 1.317, 95%CI: 1.005-1.727. Further subgroup analysis based on ethnicity demonstrated the association with the risk of TB in all genotype models of the FokI polymorphism for Han population. Meta-regression analysis also indicated that ethnicity could be a potential source of heterogeneity in the FokI and BsmI polymorphisms in the VDR gene. However, publication year was another source of heterogeneity for the TaqI polymorphism. In summary, the FokI polymorphism in the VDR gene was found to increase the risk of TB in the HIV-negative population, both overall and in Asian populations. The findings presented in this paper could provide clues for preventing TB from the perspective of vitamin D supplementation, which is a controversial topic in the field of medicine and health.

The Role of Vitamin D and Vitamin D Receptor Gene Polymorphisms in the Course of Inflammatory Bowel Disease in Children.

Background: The etiopathogenesis of inflammatory bowel disease (IBD) is still unclear. Prior studies suggest genetic components that may influence the incidence and severity of the disease. Additionally, it was shown that low levels of serum vitamin D may have an impact on the clinical course of the disease due to its effect on the immunological system. Methods: We aimed to investigate the correlation between the incidence of vitamin D receptor (VDR) gene polymorphisms (rs11568820, rs10735810, rs1544410, rs7975232, and rs731236, commonly described as Cdx2, FokI, Bsm, ApaI, and TaqI, respectively) and vitamin D concentration with the clinical course of IBD (disease activity, extent of the intestinal lesions). Data were obtained from 62 patients with IBD (34 with Crohn's disease, 28 with ulcerative colitis), aged 3-18 years, and compared with controls (N = 47), aged 8-18 years. Results: Although there was no difference in the incidence of individual genotypes between the study groups (IBD, C) in all the polymorphisms examined, we described a significant increase in the chance of developing IBD for heterozygotes of Cdx2 (OR: 2.3, 95% CI 0.88-6.18, p = 0.04) and BsmI (OR: 2.07, 95% CI 0.89-4.82, p = 0.048) polymorphisms. The mean serum 25OHD level in patients with IBD was significantly higher compared with the controls (19.87 ng/mL vs. 16.07 ng/mL; p = 0.03); however, it was still below optimal (>30 ng/mL). Furthermore, a significant correlation was found between vitamin D level and TaqI in patients with IBD (p = 0.025) and patients with CD (p = 0.03), as well as with the BsmI polymorphism in patients with IBD (p = 0.04) and patients with CD (p = 0.04). A significant correlation was described between the degree of disease activity and genotypes for the FokI polymorphism in patients with UC (p = 0.027) and between the category of endoscopic lesions and genotypes for the Cdx2 polymorphism also in patients with UC (p = 0.046). Conclusions: The results suggest a potential correlation of VDR gene polymorphism with the chance of developing IBD, and the clinical course of the disease requires further studies in larger group of patients. Vitamin D supplementation should be recommended in both children with inflammatory bowel disease and in healthy peers.

Gene Variants of Vitamin D Receptor (TaqI T > C (rs731236) and BsmI G > A (rs1544410) in Urolithiasis

Background: Urolithiasis is the most prevalent uronephrologic disorder caused by genetic, environmental factors, and metabolic defects. Objectives: The present study aimed to find a possible association between the vitamin D receptor (VDR) TaqI and the BsmI gene polymorphisms in relation to the serum levels of calcium (Ca) and vitamin D and the risk of urolithiasis. Methods: This case-control study was conducted on 68 children with urolithiasis and 67 healthy controls for the VDR gene polymorphisms using the polymerase chain reaction-restriction length polymorphism method. Results: The frequency of TaqI C allele was 36% in patients compared to 32.1% in controls (P = 0.49). A significantly higher frequency of the TaqI CC genotype was found among patients in the age group > 5 to 10 years. No significant difference was detected in the frequency of the BsmI A allele between patients (41.9%) and controls (42.5%, P = 0.91). However, a significantly lower frequency of the BsmI AA genotype was detected compared to those patients with Ca levels of > 10.8 mg/dL among patients with Ca levels of ≤ 10.8 mg/dL. Conclusions: Based on the results, a lack of an association between the VDR TaqI and BsmI polymorphisms with the risk of urolithiasis among children from Western Iran. However, a higher frequency of the TaqI CC genotype was found in the age group > 5 to 10 years. In addition, lower levels of Ca in patients were related to a significantly lower frequency of the BsmI AA genotype. The VDR gene BsmI polymorphism might affect the calcium level and the calcium metabolism in urolithiasis.

Vitamin D receptor gene polymorphisms, bioavailable 25-hydroxyvitamin D, and hepatocellular carcinoma survival.

Little is known about the role of vitamin D receptor polymorphisms and their interaction with vitamin D status in hepatocellular carcinoma (HCC) prognosis. We evaluated the association of TaqI, BsmI, Cdx-2, and ApaI polymorphisms, individually and in combination, with liver cancer-specific (LCSS) and overall survival (OS) among 967 patients with newly diagnosed HCC. Subsequently, we examined whether these polymorphisms modified the association between serum bioavailable 25-hydroxyvitamin D (25OHD) concentrations and survival. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). During a median follow-up of 1017 days, 393 deaths occurred, with 360 attributed to HCC. Having TaqI G allele (HRper allele = 1.30, 95% CI = 1.08 to 1.57) or BsmI T allele (HRper allele = 1.41, 95% CI = 1.01 to 1.99) was associated with worse LCSS. Carrying increasing numbers of protective alleles was associated with superior LCSS (HR6-8 vs 0-3 = 0.52, 95% CI = 0.34 to 0.80). The inverse association of bioavailable 25OHD with LCSS was statistically significant only in patients with TaqI AA (HRQuartile 4 vs Quartile 1 = 0.63, 95% CI = 0.44 to 0.92), BsmI CC (HRQuartile 4 vs Quartile 1 = 0.62, 95% CI = 0.44 to 0.88), and 6 to 8 protective alleles (HRQuartile 4 vs Quartile 1 = 0.45, 95% CI = 0.23 to 0.87). Similar associations were observed for OS. Patients carrying wild-type TaqI, BsmI, or more protective alleles had improved survival and might benefit from optimizing bioavailable 25OHD status.

Pulmonary tuberculosis epidemiology and genetics in Kazakhstan.

Tuberculosis (TB) is a major public health emergency in many countries, including Kazakhstan. Despite the decline in the incidence rate and having one of the highest treatment effectiveness in the world, the incidence rate of TB remains high in Kazakhstan. Social and environmental factors along with host genetics contribute to pulmonary tuberculosis (PTB) incidence. Due to the high incidence rate of TB in Kazakhstan, our research aimed to study the epidemiology and genetics of PTB in Kazakhstan. 1,555 participants were recruited to the case-control study. The epidemiology data was taken during an interview. Polymorphisms of selected genes were determined by real-time PCR using pre-designed TaqMan probes. Epidemiological risk factors like diabetes (χ2 = 57.71, p < 0.001), unemployment (χ2 = 81.1, p < 0.001), and underweight-ranged BMI (<18.49, χ2 = 206.39, p < 0.001) were significantly associated with PTB. VDR FokI (rs2228570) and VDR BsmI (rs1544410) polymorphisms were associated with an increased risk of PTB. A/A genotype of the TLR8 gene (rs3764880) showed a significant association with an increased risk of PTB in Asians and Asian males. The G allele of the rs2278589 polymorphism of the MARCO gene increases PTB susceptibility in Asians and Asian females. VDR BsmI (rs1544410) polymorphism was significantly associated with PTB in Asian females. A significant association between VDR ApaI polymorphism and PTB susceptibility in the Caucasian population of Kazakhstan was found. This is the first study that evaluated the epidemiology and genetics of PTB in Kazakhstan on a relatively large cohort. Social and environmental risk factors play a crucial role in TB incidence in Kazakhstan. Underweight BMI (<18.49 kg/m2), diabetes, and unemployment showed a statistically significant association with PTB in our study group. FokI (rs2228570) and BsmI (rs1544410) polymorphisms of the VDR gene can be used as possible biomarkers of PTB in Asian males. rs2278589 polymorphism of the MARCO gene may act as a potential biomarker of PTB in Kazakhs. BsmI polymorphism of the VDR gene and rs2278589 polymorphism of the MARCO gene can be used as possible biomarkers of PTB risk in Asian females as well as VDR ApaI polymorphism in Caucasians.

The role of VDR and TNF gene polymorphism in cytokine regulation in type I diabetes mellitus of the Uzbek population, Samarkand, Uzbekistan

Abstract. Rayimova F, Dushanova G, Alikulov B, Kamalov Z, Ruzibakieva M, Nabiyeva F, Rajabov A. 2024. The role of VDR and TNF gene polymorphism in cytokine regulation in type I diabetes mellitus of the Uzbek population, Samarkand, Uzbekistan. Biodiversitas 25: 1329-1336. After 2000, diabetes became one of the most common diseases in the world. Special attention is paid to the research to determine the variability of genetic processes in patients in the origin and development of this disease. The article is devoted to the study of the connection between the polymorphism of genotypes GG, GA, AA polymorphism BsmI of the VDR- (Vitamin D receptor) gene and GG, GA of the TNF-A-308G/A- (Tumor necrosis factor A) gene with the regulation of cytokines TNF? and IL6-Interleykin 6 in sick and healthy individuals of the Samarkand region of the Uzbek population. The analysis of the BsmI polymorphism of the VDR gene and TNF-A-308G/A indicates the involvement of certain genotypes in the Type 1 Diabetes Mellitus (T1DM) pathogenesis. The age of onset of the disease in the studied population is from 7 years, but the increase in the incidence of diseases begins from 10 years. Type 1 diabetes is more common in females. Studies of the relationship between the cytokines TNF? and IL6 show their high content depending on the genotypes GG, GA, and AA of the BsmIA polymorphism of the VDR gene and the genotypes GG and GA of the gene. TNF-A-308G/A. However, the highest rates were recorded in individuals with the AA genotype of the BsmI polymorphism of the VDR gene. The obtained results can serve as fundamental knowledge in revealing and explaining the mechanisms of cytokinin control in people with diabetes in different populations of the same nation.

Vitamin D receptor gene BsmI (rs1544410) polymorphism: role in multiple sclerosis and genotype-phenotype correlations.

Multiple sclerosis (MS) has a complex pathophysiology which depends on many endogenous and exogenous factors. Vitamin D involvement has been largely studied in MS. The large distribution of the vitamin D receptor (VDR) in different immune cells is suggestive of an immunomodulatory role. The VDR gene polymorphisms have been proposed as potential risk factors for MS development or evolution with non-conclusive results. We conducted a cross-sectional study including patients ≥ 18 years, with a diagnosis of relapsing remitting MS according to the McDonald Criteria and having a minimum follow-up period of one year after starting a disease modifying therapy. Two study groups were compared based on the Multiple Sclerosis Severity Scale or MSSS: "a slow progressor" group for an MSSS ≤ 5, and a "fast progressor" group for an MSSS > 5. The rs1544410 VDR gene polymorphism was studied for all patients. Eighty patients were included. The fast progressor groups had a higher EDSS at onset, a higher total number of relapses, more frequent and shorter time to secondary progression. The progression profile was not statistically different between genotypes and alleles of the VDR gene polymorphism rs1544410. The CC genotype and wild-type allele exhibited a more aggressive disease phenotype with a higher number of relapses the first year, shorter time to secondary progression and cerebral atrophy on assessment. Our results suggest potential genotype-phenotype correlations for the rs1544410 VDR gene polymorphism in the disease course of MS. Future research on a larger scale is needed to confirm these findings.

Vitamin D receptor gene polymorphism in Egyptian multiple sclerosis patients

One of the most common neurological illnesses in the world is multiple sclerosis (MS), a chronic autoimmune demyelinating disease of the central nervous system (CNS). MS has both a genetic and an environmental origin. In terms of environmental factors, vitamin D deficiency is one of the most important risk factors and closely connected with gene polymorphisms involved in vitamin D metabolism, transport, or activity. Since vitamin D activity requires a receptor-mediated response, any changes to the vitamin D receptor (VDR) may have an effect on the pathophysiology of the disease. In this study, we aimed to identify the relationship between VDR gene polymorphisms, FokI A&gt;G (rs2228570), ApaI A&gt;C (rs7975232) and BsmI C&gt;T (rs1544410) and MS. FokI, ApaI and BsmI genotypes were determined in 50 patients with relapsing remitting MS (RRMS) and in 50 control subjects. DNA was isolated from blood samples, and then FokI, ApaI and BsmI gene polymorphisms were identified using allelic discrimination real time polymerase chain reaction (PCR) assay. The distribution of FokI, ApaI and BsmI polymorphisms did not show any significant differences between MS patients and controls. Thus, we concluded that there is no association between the studied VDR gene polymorphisms and MS.

Association between Vitamin D Receptor Fokl and Bsml Gene Polymorphism and Diabetes Mellitus in Nepalese Population

Vitamin D being involved in the secretion of insulin is a known fact. Moreover, studies have shown that steroids might be a factor in influencing insulin sensitivity. Vitamin D receptor (VDR), a factor required for genetic regulation involving vitamin D, thus can be regarded as a good candidate for Diabetes Mellitus (DM). Several studies have been conducted on the association between VDR polymorphism and the risk of DM but did not provide clear-cut answers. This study was conducted to search for the involvement of FokI and BsmI polymorphisms of the VDR gene with DM in a Nepalese population. A total of 200 blood samples were collected; 100 from clinically diagnosed DM patients and 100 from healthy controls. DNA was extracted from blood by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis, where FokI and BsmI primers as well as restriction enzymes were used. After restriction digestion, SNPs of FokI (T/C) [rs2228570] and BsmI (A/G) [rs1544410] were assayed using agarose gel electrophoresis. As patients and controls were likened for genotype distribution and allelic frequencies, it was found that the frequency of VDR gene BsmI rs1544410 differed significantly (p &lt; 0.05, each) between cases and control whereas A allele was dominant (91%) in healthy controls with Odd ratio (OR) of 0.55, unlike VDR Fokl were not significantly associated between subjects and control. The data obtained from this research suggests that the VDR gene (especially BsmI) is associated with the risk of DM.

Prevalence of Vitamin D Receptor Genes Polymorphisms in People with Pulmonary Tuberculosis: A Systematic Review and Meta-Analysis.

Polymorphisms in the vitamin D receptor (VDR) play an effective role in the susceptibility of pulmonary tuberculosis (TB). Given the importance of this polymorphism and its association with pulmonary TB, this study aimed to investigate the prevalence of VDR polymorphisms in people with pulmonary TB. The search process was performed from 2009 to 2023 according to PRISMA (Preferred reporting items for systematic reviews and meta-analyses). The strengthening of the reporting of observational studies in epidemiology (STROBE) checklist was used to qualify the articles. The data was entered into STATA version 14 software, then the fixed effects model and the random effects model, effect size (ES), and Q test (P < 0.10) were used for data analysis at a confidence interval level (CI) of 95%. Two-sided statistical tests were considered with α=0.05. In this research, 28 articles were analyzed. Polymorphisms showed a significant relationship with susceptibility to pulmonary TB (P = 0.000), and significant heterogeneity (P = 0.000) was seen between polymorphisms. FokI (95% CI: 0.39-0.46, P = 0.000, ES = 43%), ApaI (95% CI: 0.31-0.48, P = 0.000, ES = 39%) and BsmI (95% CI: 0.24-0.50, P = 0.000, ES = 37%) showed the most frequent gene polymorphisms after TaqI (95% CI: 0.34-0.77, P = 0.000, ES = 56%). ApaI, BsmI, FokI, and TaqI polymorphisms were found in patients suffering from pulmonary TB. Polymorphisms related to the TaqI gene were the most frequent. Controlling and prescribing vitamin D may be needed in these patients.

Vitamin D Receptor Polymorphisms in a Spanish Cohort of Parkinson's Disease Patients.

Background: Vitamin D receptor (VDR) is a nuclear hormone receptor widely expressed in the substantia nigra. Its association with an increased risk of Parkinson's disease (PD) is based on vitamin D deficiency and/or different polymorphisms in its gene receptor. This fact has been demonstrated by several case-control studies. Materials and Methods: Consequently, we investigated the association between VDR ApaI, BsmI, FokI, and TaqI gene polymorphisms and PD in a Spanish cohort that included 54 cases and 17 healthy controls. The detection of single nucleotide polymorphisms (SNPs) was performed using a polymerase chain reaction-restriction fragment length polymorphism. Results: Our data indicate that the SNPs were not associated with the age of onset of PD, nor with the occurrence of motor symptoms. However, only BsmI polymorphism was significantly associated with PD in this Spanish cohort. In fact, BsmI genotype was five times higher among PD patients than among controls, and the A allele was considered as a genetic risk for PD. Additionally, the combination of FokI and BsmI polymorphisms was significantly associated with PD and could represent a risk factor. Conclusion: We conclude that ApaI, TaqI, and FokI polymorphisms were not associated with PD, but BsmI could be a risk factor for PD in this randomized population.

Assessment of vitamin D status and vitamin D receptor polymorphism in Egyptian children with Type 1 diabetes

BackgroundThe endocrine system of vitamin D regulates about 3 % of the human genome. Vitamin D exerts its actions via a nuclear vitamin D receptor (VDR) which in turn regulates insulin secretion from the pancreas. VDR gene polymorphisms could have an impact on how autoimmune illnesses like Type 1 diabetes mellitus (T1DM) develop. We aimed to explore the relation between T1DM and VDR gene polymorphisms in Egyptian diabetic children and their siblings. MethodsEnzyme-linked immunosorbent assay was used to quantify 25(OH) vitamin D in the study, which had 179 participants (group 1 = 85 diabetic children, group 2 = 57 siblings of the patients, group 3 = 37 healthy controls). Real-time polymerase chain reaction (RT-PCR) was used to analyze the genotyping of the VDR gene polymorphisms Apa-I (rs7975232), Fok-I (rs2228570), Taq-I (rs731236) and Bsm-I (rs1544410). ResultsThe mean serum 25(OH) vitamin D levels was significantly lower in T1DM patients (14.99 ± 9.24 ng/mL) and siblings (16.31 ± 7.96 ng/mL) compared to the controls (19.48 ± 7.42 ng/mL) (p = 0.031). The genotypes distribution of VDR Fok-I (rs2228570) and Bsm-I (rs1544410) polymorphisms showed a significant difference between patients, siblings and controls as P = 0.001 and 0.026 respectively, while the VDR ApaI and TaqI polymorphisms did not. FokI-A allele frequency was significantly lower in T1DM patients and siblings than in controls (p < 0.001). FokI-AA genotype had a statistical significant higher vitamin D levels than other genotypes with p value of 0.024. ConclusionOur study found that T1DM children had lower vitamin D levels, and VDR FokI and BsmI gene polymorphisms were linked to T1DM in Egyptian children. Determining the relationship between vitamin D levels and VDR polymorphisms, particularly the FokI and other genetic analyses may aid in the early diagnosis of T1DM in children.

The effect of BsmI (rs1544410) single nucleotide polymorphism of vitamin D receptor (VDR) on insulin resistance in healthy children and adolescents: a cross-sectional study

The increasing prevalence of metabolic syndrome, type 2 diabetes, and insulin resistance are driven by complex interactions between genetic and environmental factors. One of the single nucleotide polymorphisms (SNPs) in the VDR gene associated with vitamin D levels is the rs1544410 SNP. This study examined the association of the rs1544410 polymorphism with insulin resistance to predict and screen for possible association with type 2 diabetes and target these individuals for appropriate treatment. This cross-sectional study examined 270 children and adolescents aged 9 to 18 years. Anthropometric and biochemical parameters were determined. Insulin resistance/sensitivity was determined using Quicki, HOMA-IR, MacAuley, Revised MacAuley, Bennetts, FIRI and insulin-to-glucose ratio. The BsmI single nucleotide polymorphism (rs1544410) was determined using the PCR-RFLP method after extracting DNA from peripheral blood collected from fasted subjects, and the resulting data were analyzed using SPSS software and statistical tests.According to linear regression analysis, a significant difference was found in Insulin to glucose ratio, FIRI and HOMA-IR indices between Bb / bb and BB genotypes and it was observed that individuals with BB genotype polymorphism of BsmI vitamin D receptor gene, after Adjustment of age, sex, BMI are at greater risk for insulin resistance and type 2 diabetes.This study demonstrated that those with the BB genotype of VDR BsmI polymorphism were at higher risk for insulin resistance and developing type 2 DM.

Influence of the BsmI polymorphism of the vitamin D receptor gene on the levels of vitamin D, inflammatory and oxidative stress profile in patients with cystic fibrosis supplemented with Colecalciferol megadose

Evaluate the influence of the BsmI polymorphism of the vitamin D receptor gene on vitamin D levels, and inflammatory and oxidative stress markers in patients with Cystic Fibrosis supplemented with cholecalciferol megadose. We performed a single-arm, non-randomized pre- and post-study of 17 patients aged 5 to 20 years with cystic fibrosis diagnosed with vitamin D insufficiency/deficiency 25-hydroxy vitamin< 30ng/mL. Individuals were genotyped for the BsmI polymorphism of the vitamin D receptor gene and all received cholecalciferol supplementation of 4,000 IU daily for children aged 5 to 10 years and 10,000 IU for children over 10 years of age for 8 weeks. Interviews were conducted with personal data, sun exposure, anthropometric and blood samples of 25-hydroxy vitamin parathormone, serum calcium, ultrasensitive C-reactive protein, alpha 1 acid glycoprotein, total antioxidant capacity, malondialdehyde and kidney and liver function. Inter- and intra-group assessment was assessed by paired t-test Anova test or its non-parametric counterparts. The individuals were mostly male and reported no adverse effects from the use of supplementation, 64% had 25-hydroxy vitamin levels >30ng/mL. Patients with BB and Bb genotypes showed increased serum levels of 25-hydroxy vitamin. The group with BB genotype showed a reduction in alpha 1 acid glycoprotein. And individuals with the bb genotype had high levels of malondialdehyde compared to the pre-intervention time. It is concluded that variations of the BsmI polymorphism of the vitamin D receptor gene have different responses in vitamin D levels and markers of inflammation and oxidative stress.

Оценка распространенности полиморфизмов в генах, кодирующих рецептор витамина D и фермент 1α-гидроксилазу, у жителей Москвы и Московской области для составления персонализированной схемы лечения препаратами витамина D

The use of vitamin D preparations in the treatment of several diseases is of great interest, given its multiple and diverse effects. However, despite the positive experience with cholecalciferol, there are patients in whom clinical efficacy is either absent or poorly expressed, and similar data are available in published studies. Polymorphisms in genes encoding the vitamin D receptor and the 1α-hydroxylase enzyme are a necessary addition to laboratory parameters to allow proper selection of the dose, regimen, form, and chemical structure of the vitamin D preparation. Objective. To assess the prevalence of polymorphisms in genes encoding the vitamin D receptor and the 1α-hydroxylase enzyme in residents of Moscow and the Moscow Region. Patients and methods. The study included 3000 patients living in Moscow and the Moscow Region, aged 2 to 77 years, treated with vitamin D preparations in Professor Kalinchenko Clinic between October 10, 2020, and December 23, 2023. Patients were genotyped by direct sequencing for two markers of susceptibility to vitamin D deficiency: variants in the vitamin D receptor gene (VDR, BsmI Polymorphism, rs1544410) and the 1α-hydroxylase enzyme gene (CYP27B1, g.57764205A&gt;G; rs464656536). Statistical data processing was performed using IBM SPSS Statistics 23.0 software (USA). Results. Polymorphism in the gene encoding the 1α-hydroxylase enzyme was detected in 2595 (89.5%) of 3000 patients, of which heterozygotes (A/G) in 1434 (47.8%) and homozygotes (A/A) in 1161 (38.7%). Polymorphism in the gene encoding VDR was detected in 429 (14.3%) patients, of which heterozygotes (C/T) in 1338 (44.6%) and homozygotes (C/C) in 1233 (41.1%). The combination of polymorphisms in the CYP27B1 and VDR genes was detected in 375 (12.5%) patients, the absence of polymorphisms in two genes – in 351 (11.7%). Discussion. In the presence of CYP27B1, g.57764205A &gt; G; rs4646536 in the gene encoding the 1α-hydroxylase enzyme, the intensity of calcitriol formation is reduced, which explains the lack of effect of therapy with cholecalciferol preparations. In the presence of VDR, BsmI Polymorphism, rs1544410 in the gene encoding the vitamin D receptor, the sensitivity of the receptor to hormone D is reduced, which explains the lack of clinical effects of therapy with vitamin D preparations in standard therapeutic doses. The most difficult-to-treat clinical manifestations of vitamin D deficiency were found in patients with polymorphisms in two genes encoding both VDR and 1α-hydroxylase, which amounted to 12.5% (375 people) of the total number of patients; among all patients examined, only 351 (11.7%) did not have polymorphisms in these two genes. Conclusion. Controversial literature data and clinical effects of vitamin D therapy are due to variants in the VDR and/or CYP27B1 genes. Knowledge of genetics allows individualization of the dose, form, and chemical activity of the vitamin D preparation, which is the key to success of therapy. Key words: vitamin D, calcidiol, calcitriol, vitamin D receptor, cholecalciferol, 1α-hydroxylase

Vitamin D and Vitamin D Receptor FokI, ApaI, and BsmI Gene Polymorphisms and their Relation with the Risk of Breast Carcinoma: A Case-control Study

Introduction: Breast cancer stands as the leading cause of mortality among women in developing nations. The potential role of Vitamin D in mitigating the incidence of breast cancer is thought to stem from its ability to impede cell proliferation by interacting with the Vitamin D Receptor (VDR). The VDR gene is responsible for encoding the VDR, which plays a pivotal role in mediating the effects of vitamin D. Aim: To analyse vitamin D levels and the association of VDR FokI, ApaI, and BsmI genotypic distribution frequency with the risk of breast cancer. Materials and Methods: The case-control study included 220 samples, including 110 breast cancer patients and 110 agematched control women aged 30-70 years. The Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) genotyping was performed using Deoxyribonucleic acid (DNA) extracted from blood, and the circulating levels of 25-hydroxyvitamin D by case/control were estimated by chemiluminescence immunoassay. Results: The 3’ VDR polymorphism BsmI sequence showed minimal association with breast cancer risk. The bb genotype had a significantly lower odds ratio of 0.056 (p-value&lt;0.05). Conversely, the BB and Bb genotypes exhibited no statistically significant associations with odds ratios of 1.76 (95% CI: 0.36-8.54; p-value&gt;0.05) and 1.30 (95% CI: 0.27- 6.25; p-value&gt;0.05), respectively. Isolated analysis of the FokI variant revealed a significant association with increased breast cancer risk, with odds ratios of 5.49 (FF) and 6.00 (Ff), both demonstrating statistical significance (p-value&lt;0.05), and a Chi-square value of 0.006. Additionally, the p-value for serum Vitamin D levels was found to be highly significant at p-value&lt;0.001, indicating that the levels were significantly lower in individuals newly diagnosed with breast cancer compared to those in the healthy control group. Conclusion: The study found a significant link between breast cancer susceptibility and VDR (FokI) polymorphism FF and Ff genotypes, with minimal impact observed for (BsmI) polymorphism bb genotype. This implies that certain genetic variations, especially in the FokI polymorphism of the VDR gene, are associated with an elevated risk of breast cancer.

ОСТЕОПЕНИЯ КАК ПРОЯВЛЕНИЕ ИДИОПАТИЧЕСКОЙ ГИПЕРКАЛЬЦИУРИИ У ДЕТЕЙ

Idiopathic hypercalciuria (IH) can lead to the development of osteopenia and osteoporosis in childhood. Vitamin D and its receptor, encoded by the VDR gene, play a major role in maintaining normal calcium levels in bone tissue. The purpose of the study: to study the state of bone mineral density in children with idiopathic hypercalciuria and the association of vitamin D receptor (VDR) gene polymorphisms with osteopenia. Materials and methods. The study included 35 children with IH aged 5 to 17 years with a history of fractures and/or decompensated caries. The children were subjected to X-ray densitometry to calculate the Z score in the lumbar spine and proximal femurs. A group of children with IH (n=20) underwent a study of the level of 25-OH vitamin D in blood plasma and a genetic study for the presence in genetic polymorphisms of the VDR gene: BsmI Polymorphism IVS10+283G&gt;A, A-3731G (Cdx2), FokI Polymorphism; Ex4+4T&gt;C. Results. A decrease in BMD was detected in 68.6% of children with IH, while 2 patients aged 15 and 17 years had signs of osteoporosis. The homozygous Ex4+4 CC genotype of the VDR (Fokl) gene was significantly more common in patients with idiopathic hypercalciuria. For the remaining genotypes of the VDR enzyme gene, no statistically significant differences could be detected (p&gt;0.05). Conclusion. Idiopathic hypercalciuria in children often leads to a decrease in bone mineral density, which should be taken into account when treating children with this pathology. A genetic predictor of osteopenia in children with IH may be the carriage of the homozygous genotype (rare allele) Ex4+4 CC of whose VDR (Fokl) gene, the study can be used for early diagnosis and prevention of the development of osteoporosis.

Genetic Risk of Rheumatoid Arthritis: A Case Control Study

Vitamin D effects are mediated by vitamin D receptors (VDRs), which are influenced by various genetic polymorphisms, including ApaI and BsmI. These polymorphisms have been linked to several diseases, including rheumatoid arthritis (RA). This study aimed to compare the frequency and association of VDR ApaI and BsmI gene polymorphisms, serum 25-hydroxy vitamin D (25-(OH)-D) levels, and calcium (Ca) levels between a RA group and a matched healthy control group. In one hundred RA patients and fifty healthy controls, the genotypes of the VDR ApaI and BsmI gene polymorphisms were analyzed using polymerase chain reaction restriction fragment length polymorphisms (PCR-RFLP). Both Serum 25-(OH)-D level and calcium level were measured in the two groups. There was no significant difference between the cases and controls regarding the VDR ApaI gene polymorphism (p = 0.89). A significant difference was observed between the cases and controls in terms of the VDR BsmI gene polymorphism (p = < 0.001). The serum levels of 25-(OH)-D and calcium were significantly lower in the RA group compared to the control group (p = 0.04 and < 0.001 respectively). Significantly higher serum vitamin D levels were associated with the aa genotype (p = 0.007). Significantly increased calcium levels were associated with the AA genotype (p = 0.02). No significant difference was found among BsmI polymorphisms regarding vitamin D and Ca levels (p = 0.25 and 0.87 respectively). Vitamin D receptor gene BsmI polymorphism but not ApaI polymorphism could be a marker of RA susceptibility. Vitamin D and Ca levels are negatively affected by RA. Vitamin D receptor gene ApaI polymorphism contributes to vitamin D and Ca levels.