Vitamin D-binding Protein Gene Research Articles

Serum 25-Hydroxyvitamin D, Vitamin D Receptor, and Vitamin-D-Binding Protein Gene Polymorphisms and Risk of Dementia Among Older Adults With Prediabetes.

The association between vitamin D and dementia risk in those with prediabetes remains uncertain. We aimed to evaluate the association of serum 25-hydroxyvitamin D (25OHD) with incident dementia among older adults with prediabetes, and examine whether apolipoprotein E (APOE) genotypes, vitamin D receptor (VDR), and vitamin-D-binding protein (VDBP) gene polymorphisms may modify this association. A total of 34237 participants aged ≥60 with prediabetes (HbA1c <6.5% and ≥5.7%) and without dementia at baseline were included from the UK Biobank. Serum 25-hydroxyvitamin D (25OHD) was measured using chemiluminescent immunoassay method. The primary outcome was incident all-cause dementia. Secondary outcomes included incident Alzheimer's disease (AD) and vascular dementia, respectively. The VDR and VDBP gene polymorphisms included single nucleotide polymorphisms of rs7975232, rs1544410, rs2228570, rs731236, and rs7041, rs4588, respectively. During a median follow-up of 11.8 years, 941 (2.7%) participants developed incident all-cause dementia. Overall, serum 25OHD was inversely associated with all-cause dementia (per standard deviation increment, adjusted hazard ratio: 0.82; 95% confidence interval: 0.75, 0.89). Similar trends were found for incident AD and vascular dementia. Furthermore, there was a stronger inverse relationship between serum 25OHD and all-cause dementia among VDR rs7975232 C allele noncarriers (p-interaction < 0.05). However, APOE Ɛ4, other VDR, and VDBP gene polymorphisms did not significantly modify the relation of serum 25OHD with incident all-cause dementia (all p-interactions >.05). There was an inverse association between serum 25OHD and incident dementia among older adults with prediabetes, especially in VDR rs7975232 AA allele carriers.

Association of functional, inherited vitamin D-binding protein variants with melanoma-specific death.

It is unclear whether genetic variants affecting vitamin D metabolism are associated with melanoma prognosis. Two functional missense variants in the vitamin D-binding protein gene (GC), rs7041 and rs4588, determine 3 common haplotypes, Gc1s, Gc1f, and Gc2, of which Gc1f may be associated with decreased all-cause death among melanoma patients based on results of a prior study, but the association of Gc1f with melanoma-specific death is unclear. We investigated the association of the Gc1s, Gc1f, and Gc2 haplotypes with melanoma-specific and all-cause death among 4490 individuals with incident, invasive primary melanoma in 2 population-based studies using multivariable Cox-proportional hazards regression. In the pooled analysis of both datasets, the patients with the Gc1f haplotype had a 37% lower risk of melanoma-specific death than the patients without Gc1f (hazard ratio [HR] = 0.63, 95% confidence interval [CI] = 0.47 to 0.83, P = .001), with adjustments for age, sex, study center, first- or higher-order primary melanoma, tumor site, pigmentary phenotypes, and Breslow thickness. Associations were similar in both studies. In pooled analyses stratified by Breslow thickness, the corresponding melanoma-specific death HRs for those patients with the Gc1f haplotype compared with those without Gc1f were 0.89 (95% CI = 0.63 to 1.27) among participants with tumor Breslow thickness equal to or less than 2.0 mm and 0.40 (95% CI = 0.25 to 0.63) among participants with tumor Breslow thickness greater than 2.0 mm (Pinteraction = .003). Our findings suggest that individuals with the GC haplotype Gc1f may have a lower risk of dying from melanoma-specifically from thicker, higher-risk melanoma-than individuals without this Gc1f haplotype.

Vitamin D receptor and vitamin D binding protein gene polymorphisms in patients with asthma: a pilot study

BackgroundThe effects of vitamin D are exerted by interaction with the vitamin D receptor (VDR) and vitamin D binding protein (VDBP). Polymorphisms in VDR or VDBP genes may affect vitamin D levels, influencing the pathogenesis of asthma and atopy. The aim of this study was to investigate the possible association of VDR and VDBP gene single-nucleotide polymorphisms (SNP), 25-hydroxyvitamin D (25(OH)D), blood eosinophils and total IgE level in subjects with asthma in comparison with healthy individuals.MethodsThis case-control study enrolled 63 subjects with asthma (45 allergic and 18 non-allergic) and 32 healthy subjects were involved in the study. Sensitization of subjects to inhaled allergens was determined by a skin prick test, lung function was evaluated by spirometry. Blood eosinophil count was determined by standard methods. Serum 25(OH)D and total IgE levels were evaluated by ELISA. Polymorphisms in the VDR and VDBP genes on the 12q13.11 and 4q13.3 chromosomal region were analyzed using TaqMan SNP Genotyping Assay probes.ResultsIn asthma patients with vitamin D deficiency (< 20 ng/ml) the allele G of rs11168293 of VDR was more common than in those having insufficiency (20–30 ng/ml) of vitamin D (63% and 31%, p < 0.05). Moreover, asthmatic subject with rs11168293 G allele has significant higher blood eosinophil count compared to asthmatic without the rs11168293 G allele (8.5 ± 12.3% vs. 5.1 ± 1.5%, p < 0.05). Significantly higher IgE level was found in subjects with allergic asthma with the allele A of rs7041 on VDBP gene than in those without this allele (540 ± 110 and 240 ± 80 IU/ml, p < 0.05).ConclusionsThe association of polymorphisms in VDBP and VDR gene, the rs11168293 G allele and the rs7041 A allele, with 25(OH)D, blood eosinophil and total IgE level in asthma, let us suggest that vitamin D, VDR and VDBP gene polymorphisms are important in pathogenesis of asthma despite its form in relation to atopy.

Association between Polymorphism Locus rs7041 and rs4588 in VDBP Gene and Vitamin D Status with Mortality in Sepsis Patient

Vitamin D deficiency was associated with an increased mortality risk in patients with sepsis. Loci rs7041 and rs4588 polymorphisms of the Vitamin D Binding Protein (VDBP) gene receptor caused a significantly increased risk of vitamin D deficiency in subtropical countries (Yordania). Simultaneously, similar studies for the tropics (Indonesia) have not been found yet. This study aims to analyze the association between polymorphism locus rs7041 and rs4588 in the vitamin D binding receptor gene and vitamin D status with the mortality of sepsis patients. This study was an analytical observation type with a cohort design. The relationship between the two groups was analyzed using the chi-square test/fisher test. Mutant’s polymorphism locus rs7041 in not survived patients is more than survived (65.0% vs. 35.0%) with a p-value of 0,025. The mortality risk was 1.625 times (RR 1.625 95% CI 1.044 – 2.529). The mutant’s polymorphism locus rs4588 locus in not survived patients is more than survived (70.3% vs. 29.7%) with a p-value of 0,022. The mortality risk was 1.622 times (RR 1.622 95% CI 1.095 – 2.402). Polymorphism loci rs7041 and rs4588 in not survived sepsis patients were higher mutants than the wild type. The highest vitamin D deficiency occurred in the mutant locus rs4588 (55.5%), but it was not statistically significant p &gt; 0.05. There was an association between Loci rs7041 and rs4588 polymorphisms and mortality of sepsis patients. No association was between Loci rs7041 and rs4588 polymorphisms with vitamin D status and between vitamin D status and mortality of patients with sepsis. Keywords: polymorphism, rs7041, rs4588, vitamin D, vitamin D binding protein, mortality, sepsis. https://doi.org/10.55463/issn.1674-2974.50.2.15

Vitamin D-Binding Protein and Acute Myeloid Leukemia: A Genetic Association Analysis in Combination with Vitamin D Levels

Genetic variations in the vitamin D-binding protein (VDBP) may be associated with the plasma level of serum 25-hydroxyvitamin D. Furthermore, vitamin D deficiency increases the risk of acute myeloid leukemia (AML). This study aimed to examine the potential association of VDBP genetic variants (rs7041 and rs4588) with AML susceptibility. The polymorphisms in the VDBP gene and serum 25-hydroxyvitamin D levels were analyzed in 227 AML patients and 240 healthy controls enrolled in this study. Our data revealed that rs4588 CA and AA genotypes were significantly associated with AML susceptibility (OR = 1.483, p = 0.046; OR = 2.154, p = 0.013, respectively) and also with 61.59% vitamin D deficiency in the total group of AML patients. Under the TG co-dominant and dominant models, however, the rs7041 genotypes were significantly associated with AML protection (OR < 0.6; p < 0.05). In addition, vitamin D deficiency was prevalent in vitamin-D-deficient vs. sufficient AML patients who carried rs7041 and rs4588 mutant alleles (OR ≥ 2.2). Indeed, vitamin D deficiency and its interaction with the genetic variants of VDBP could change the risk of AML. Thus, vitamin D deficiency could be considered an important molecular factor in AML risk assessment.

The causal association between genetically regulated 25OHD and chronic obstructive pulmonary disease: A meta-analysis and Mendelian randomization study

Backgrounds and objectives: Chronic obstructive pulmonary disease (COPD) is a multifactorial disease under genetic control. We present a meta-analysis to examine the associations of vitamin D binding protein (VDBP) gene rs7041 polymorphism with the risk of COPD and changes in circulating 25OHD concentrations. Methods: A literature search, quality assessment, and data extraction were conducted independently by two investigators. Data are expressed as odds ratio (OR) or weighted mean difference (WMD) with a 95% confidence interval (CI). The inverse variance weighted method (IVW) in R (version 1.1.456) was applied to calculate the Mendelian randomization coefficient. Results: A total of 13 articles with 3,667 participants were meta-analyzed. The rs7041-GT genotype was associated with a 49% reduced COPD risk (OR: 0.51, 95% CI: 0.30 to 0.88, p = 0.014) compared to the rs7041-TT genotype. Carriers of the rs7041-GT genotype had significantly higher concentrations of circulating 25OHD than those with the rs7041-TT genotype (WMD: 0.32ng/ml, 95% CI: 0.09 to 0.55, p = 0.006). Under the assumptions of Mendelian randomization, and assuming a linear logistic relationship between circulating 25OHD and COPD, an inverse association was noted after using VDBP gene rs7041 polymorphism as an instrument (WMD: -2.07, 95% CI: -3.72 to -0.41, p = 0.015). There was a low probability of publication bias. Conclusion: We observed significant associations of VDBP gene rs7041 polymorphism with the risk of COPD and changes in circulating 25OHD concentrations. Importantly, we found a causal relationship between genetically regulated 25OHD concentrations and COPD risk.

The association of vitamin D binding protein levels and genotypes with type 1 diabetes in the black South African population

BackgroundVitamin D deficiency and the vitamin D pathway have previously been associated with type 1 diabetes (T1D). The majority of vitamin D is transported through the blood bound to the vitamin D binding protein (VDBP). Two polymorphisms in the VDBP gene (rs4588 and rs7041) result in different VDBP variants and have been associated with T1D, however the results are not consistent. The association of VDBP levels and its polymorphisms with T1D have not been investigated in the black South African population. Therefore, this study aimed to determine whether rs4588, rs7041 or serum VDBP levels were associated with T1D in this population.MethodsParticipants with type 1 diabetes and controls were recruited from the greater Johannesburg area, South Africa. Participants were genotyped for rs4588 and rs7041 using PCR-RFLP and serum VDBP levels were determined by ELISA.ResultsThere was no difference in VDBP allelic or genotypic frequencies between participants with T1D and controls (rs4588 C allele frequency 0.92 vs. 0.94; p = 0.390 and rs7041 T allele frequency 0.95 vs. 0.95; p = 0.890). In univariate analysis, the rs4588 CC genotype was associated with increased serum VDBP levels, however, this association was lost with multivariate analysis. The VDBP genotypes were not associated with any other study variables. In logistic regression analysis, higher VBDP levels were associated with T1D (OR: (95% CI): 6.58 (1.45–29.9); p = 0.015), and within a linear regression analysis, T1D disease status was found to be associated with 0.044 mg/ml higher VDBP levels (p = 0.028).ConclusionsThese data suggest that serum VDBP levels are positively associated with the presence of T1D in the African population. Whether VDBP lies in the causal pathway or its elevation is an effect of T1D is uncertain and requires further investigation.

Association of VDBP (rs4588 and rs7041) gene polymorphisms with susceptibility to postpartum depression in South Indian population: A cross-sectional study

Low vitamin D levels have been implicated in postpartum depressive disorders (PPD). Our study aimed to demonstrate the association of Vitamin D Binding Protein (VDBP) genetic variants rs7041 and rs4588 with susceptibility to PPD and to investigate their possible relationship with serum vitamin D and VDBP levels in Indian women with PPD. A cross-sectional study involved 330 cases and 330 controls. Depressive symptoms were assessed using Edinburg Postnatal Depression Scale. Genotyping of SNPs was done by Taqman 5’allelic discrimination assay. Estimation of serum 25 hydroxyvitamin D [25(OH) D] and VDBP levels were done by ELISA. Serum total, free and bioavailable 25(OH) D levels were significantly lower in cases compared to controls, with similar levels of VDBP between the two groups. The study results showed that the VDBP rs4588 variant genotype AA was significantly associated with lower circulating levels of total 25(OH) D in cases. Also, the VDBP rs7041 variant TT genotype demonstrated significantly lower levels of total, free and bioavailable 25(OH) D levels in controls. However, VDBP rs7041 and rs4588 variants were not associated with PPD susceptibility. Also, VDBP haplotypes showed no association with PPD susceptibility. Our results demonstrated that VDBP polymorphisms rs4588 and rs7041 and their haplotypes are not associated with PPD susceptibility in the South Indian population. However, vitamin D levels were found to be influenced by the risk genotypes of VDBP SNPs rs4588 and rs7041.

Detection the genetic variation of vitamin D binding protein (VDBP) gene in women with osteoporosis in Mosul City

The VDBP amino acid sequence is divided into three domains and has 458 amino acids. Exon 11 in domain III has two SNPs, rs7041 and rs4588, each corresponding to one of the major VDBP kinds (VDBP1S, VDBP1F, and VDBP2). Transport of vitamin D3 to the liver and 25(O.H.)D to the kidney, 1,25(O.H.)2D transport to target organs is mediated by vitamin D-binding protein, which interacts with a particular vitamin D receptor (VDR) to explain biological activities. This study aims to determine whether the VDBP gene has three polymorphisms (rs17467825, rs7041, and rs4588) associated with women with osteoporosis in Mosul city. This study included (96) women, the age range between (35-55) years.The samples were divided into two groups, the first group included (74) women with osteoporosis, and the second group was considered a control group. In this study, DNA was extracted from the blood of all the samples included in the study (95) samples, using the method modified by the researchers. And detection of three different SNP of VDBP, (rs17467825) Polymorphism by ARMS-PCR, and (rs7041T) Polymorphism with (rs4588C) Polymorphism by RFLP-PCR. This study showed a connection between deficiency of vitamin D in women and mutation of the VDBP gene in location rs17467825.

Бронхоектатична хвороба в дітей та дефіцит вітаміну D: що первинно?

Bronchiectasis in children is a chronic polyetiological pathology, the pathogenesis of which involves a complex interaction between the host, respiratory pathogens and environmental factors. The potential contribution of vitamin D deficiency to the development of bronchiectasis in children is of particular clinical importance, given the growing prevalence of vitamin D deficiency worldwide and the significant incidence of bronchiectasis, especially among children. Clinical case. The article presents a clinical case that illustrates the development of bronchiectasis in a child with a disorder of vitamin - D-controlled pathomorphological processes, which is probably the cause of dysmorphic disorders not only in the musculoskeletal system but also in the bronchi. Genetic analysis helped to confirm the primacy of vitamin D deficiency in the development of bronchiectasis in girls. Prescribed treatment with therapeutic doses of vitamin D had a positive effect. However, unfortunately, in this case there were already partially irreversible morphological changes. Conclusions. Children with recurrent or chronic bronchopulmonary disease with impaired vitamin D metabolism have a higher risk of developing bronchiectasis. Determining the level of vitamin D-binding protein (VDBP) and genetic analysis of VDBP gene polymorphisms can be useful both for verifying the diagnosis and for personalizing the treatment of such patients. The study was conducted in accordance with the principles of the Declaration of Helsinki. Informed consent of the child’s parents was obtained for the research. No conflict of interests was declared by the authors. Key words: bronchiectasis, vitamin D deficiency, children.

Influences of Vitamin D Levels and Vitamin D-Binding Protein Polymorphisms on Nonalcoholic Fatty Liver Disease Risk in a Chinese Population

Introduction: Vitamin D-binding protein (VDBP) is correlated with nonalcoholic fatty liver disease (NAFLD) through the biological functions of regulating plasma vitamin D (VD) level and the inflammatory process. Objective: This study aims to investigate the effects of VD level and VDBP gene polymorphisms on the risk of NAFLD in a Chinese population. Methods: Plasma 25-hydroxyvitamin D₃ levels were measured and seven VDBP candidate genetic variants (rs222020, rs2282679, rs4588, rs1155563, rs7041, rs16847024, rs3733359) were genotyped among participants in this case-control study. The control group was frequency-matched to the NAFLD case group by age and gender. Correlation analysis and multiple linear regressions were used to screen determinants of 25-hydroxyvitamin D₃ levels. Multivariable unconditional logistic regression was performed to estimate odds ratio (OR) and 95% confidence interval (95% CI). The prediction capability of models containing independent factors was estimated by the area under the receiver operating characteristic curve and Hosmer-Lemeshow test. Results: Age, body mass index, and triacylglycerol were independent factors influencing VD levels. Participants with low VD levels had significantly higher prevalence of NAFLD compared to subjects with normal VD levels (p < 0.001). A low VD level contributed to increased the risk of NAFLD, independent of metabolic factors known to affect VD levels (adjusted OR = 2.282, 95% CI = 1.422–3.661, p = 0.001). Logistic regression analysis showed that individuals carrying rs7041-G allele had a significantly decreased the risk of NAFLD occurrence compared to T allele (additive model: adjusted OR = 0.814, 95% CI = 0.713–0.929, p = 0.002; codominant model: adjusted OR = 0.623, 95% CI = 0.449–0.866, p = 0.005), after adjusting for age, gender, and overweight. Stratification by multiple metabolic disorders did not alter this relationship. Moreover, we developed a simple model including age, gender, metabolic disorders, and VDBP single nucleotide polymorphism (SNP) to assess NAFLD risk, an AUC of which being 0.817, significantly higher than the model not included VDBP SNP, with Hosmer-Lemeshow test fitting well (p = 0.182). Conclusions: Low plasma VD levels may increase susceptibility to NAFLD, while rs7041-G allele in VDBP contributed to a decreased NAFLD risk among Chinese population. The VDBP variant significantly improved the capability for NAFLD risk assessment, which could be used for early screening and management of NAFLD.

Vitamin-D Binding Protein Gene Polymorphisms and Serum 25-Hydroxyvitamin-D in a Turkish Population.

The rs7041 and rs4588 polymorphisms found in the GC gene, encoding vitamin D-binding protein (DBP), have distinct biochemical phenotypes. The aim of this study was to investigate vitamin D parameters with these polymorphisms, in individuals with possible vitamin D deficiency. The most common (49% of the cohort) genotype in rs7041 was GT, especially among individuals with high levels of free 25(OH)D calculated but with low levels of bioavailable 25(OH)D, and in rs4588 it was AC in particular among the individuals with low levels of bioavailable 25(OH)D. The most common phenotypes were Gc1s/2 (35.3%) and Gc1s/1s (31.4%), and Gc1f/1f was rare (5.9%). The variations in free and bioavailable 25(OH)D levels among healthy Turkish individuals may be attributed to the variations in total 25(OH)D as well as GC gene polymorphisms. The Turkish population shares a similarity for allele frequencies of rs7041 with the European population and similarity for allele frequencies of rs4588 with Gujarati Indians, and this may also be important in relation to certain ethnic populations showing associations between vitamin D and COVID-19.

Vitamin D and the Risk of Non-Melanoma Skin Cancer: A Systematic Literature Review and Meta-Analysis on Behalf of the Italian Melanoma Intergroup.

Simple SummaryVitamin D has been extensively studied in relation to cancer risk at several body sites, but its relationship with non-melanoma skin cancer (NMSC), the most frequent malignancy in humans, is still unclear. Here, we performed a systematic literature search and meta-analysis of published studies and did not find convincing evidence that a causal association exists between vitamin D intake (from foods and supplements), vitamin D blood concentration, or polymorphisms of the genes coding for the vitamin D receptor and binding protein, and NMSC risk.We aimed to provide a comprehensive overview of the link between vitamin D and non-melanoma skin cancer (NMSC). For this purpose, we conducted a systematic literature review (updated to 3 February 2021) and meta-analysis of the studies reporting on the association between vitamin D intake (from diet and supplements) and blood concentration, polymorphisms of the vitamin D receptor (VDR) and vitamin D binding protein (VDBP) genes, and the risk of NMSC. Random effects meta-analysis models were fitted to merge study-specific risk estimates into summary relative risk (SRR) and corresponding 95% confidence intervals (CI). Twenty-four studies altogether were included. There was a suggestive association between increasing serum/plasma vitamin D concentration and NMSC risk (SRR for highest vs. lowest concentration 1.67, 95%CI 0.61–4.56), although with large heterogeneity across studies (I2 = 91%). NMSC risk was associated with highest vitamin D intake in observational studies but not in clinical trials. Finally, there was no significant association between any polymorphism of the VDR and VDBP genes and NMSC risk. In conclusion, no strong relationship between vitamin D metabolism and NMSC risk appears to exist according to our systematic review and meta-analysis, although some findings are worthy of further investigation.

Association Between Vitamin D Receptor (VDR) and Vitamin D Binding Protein (VDBP) Genes Polymorphisms to Endometriosis Susceptibility in Iranian Women.

Endometriosis is a chronic inflammatory disease that has been reported to be associated with immune system dysfunction. On the other hand, the effect of Vitamin D as an immune modulator and its relation with several autoimmune and inflammatory diseases has been previously investigated. Moreover, several studies have reported the polymorphisms of VDR and VDBP genes can change the functions of these molecules. Therefore, these polymorphisms may be influential on endometriosis pathogenesis. In this study, we aimed at evaluating the association between VDR gene (FokI (F/f), BsmI (B/b), ApaI (A/a), TaqI (T/t)), and VDBP gene (GC*1S, GC*1F, and GC*2) polymorphisms with endometriosis in Iranian women population. This case-control study was performed on 120 women with endometriosis and 110 healthy women. ARMS-PCR and PCR-RFLP methods were used to inspect polymorphisms in VDR and VDBP genes, respectively. Based on the results, there was no statistically significant difference between the cases with endometriosis and control subjects in terms of genotypes and allele frequencies of VDR and VDBP gene polymorphisms. These data suggest that VDR and VDBP gene polymorphisms may have no role in endometriosis susceptibility in Iranian women.

Evaluation of Vitamin D-Binding Protein Gene Polymorphism and its Plasma Concentration in Kurdish Patients With Breast Cancer in Sanandaj, Iran

Background: Several studies have indicated that polymorphism in vitamin D pathway genes is associated with breast cancer (BC) risk. Vitamin D-binding protein (VDBP) is a vital element in the metabolism of the vitamin D. VDBP carries the serum 25(OH) D3 to cells to promote vitamin D biological functions, such as cell proliferation and apoptosis. Missense SNP (rs.7041) is a common polymorphism in VDBP gene, which shows ethnic-specific allele frequencies. Objectives: This study presents the correlation of the rs7041 (Asp432Glu) gene polymorphism and plasma concentrations of VDBP in Kurdish patients with BC in Sanandaj, Iran. Methods: This cross-sectional study included 44 premenopausal BC patients and 44 healthy subjects. Plasma VDBP concentration was measured by enzyme-linked immunosorbent assay (ELISA). The VDBP (rs7041) was genotyped by polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP). Results: VDBP level was associated with a non-significant risk of BC (P=0.397). Frequencies of individuals with VDBP (rs7041) TT, TG, and GG genotypes were 13.6%, 52.2%, and 34.09% in case group and 11.3%, 79.5%, and 9.9% in control group, respectively. Genotype GG associated with increased susceptibility to developing BC (odds ratio [OR]=5.172, CI: 1.555-17.2, P=0.007). There was a significant reverse correlation between GT genotype and BC (OR=0.282, 95% CI: 0.110-0.722, P=0.008) Conclusion: The changes in the vitamin D pathway may increase susceptibility to develop BC in the Iranian Kurdish population.

No association between the vitamin D-binding protein (DBP) gene polymorphisms (rs7041 and rs4588) and multiple sclerosis and type 1 diabetes mellitus: A meta-analysis.

The association between polymorphisms in vitamin D-binding protein (DBP) gene and the risk of multiple sclerosis (MS) and type 1 diabetes mellitus (T1DM) has been investigated in many studies, but the studies showed controversial results. The rationale for this meta-analysis was to determine whether DBP polymorphisms increases the risk of MS and T1DM by pooling data. Potentially relevant studies were searched using GWAS Catalog, PubMed, Embase, CNKI and WANFANG databases up to November 2019. The pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were performed to estimate the associations in a fixed-effects or random-effects model. A total of 13 studies were enrolled in this meta-analysis, including eight studies for MS and five for T1DM. The overall results showed that there was no significant association of DBP rs7041 and rs4588 polymorphisms with the risk of MS and T1DM under any genetic model. Similarly, subgroup analysis by ethnicity revealed that no significant association of rs7041 and rs4588 polymorphisms with the risk of MS and T1DM was observed in white or non-white racial groups. This meta-analysis provides evidence that DBP rs7041 and rs4588 polymorphisms may not be associated with an increased risk in MS and T1DM. However, these findings need further validation by larger-scale epidemiological studies and genome-wide association studies (GWASs) in different populations.

Relationship between rs2282679 gene locus polymorphism and vitamin D deficiency in college students

To investigate the relationship between vitamin D binding protein gene rs2282679 A/C polymorphism with blood vitamin D levels. A total of 286 eligible subjects were selected from one university in Hebei Province. Serum 25-hydroxylated vitamin D levels were measured by liquid chromatography-mass spectrometry, and gene chip was used for genotyping of rs2282679 locus. Statistical analysis was performed using R software. A total of 285 participants in the study completed the experiment, and result indicated that the distribution of the rs2282679 locus A/C polymorphism in the participants was consistent with the Hardy-Weinberg equilibrium. The genotype of rs2282679 was significantly associated with serum vitamin D insufficiency and deficiency(P=0. 031). Allele A was a risk factor for vitamin D insufficiency and deficiency. The OR value of allele C relative to A was 0. 65, and the genetic pattern of allele C relative to A was dominant(P=0. 03). The vitamin D-binding protein gene rs2282679 was significantly associated with serum vitamin D insufficiency and deficiency in college students, and A-allele is a risk factor accounting for vitamin D insufficiency and deficiency in college students.

Vitamin D Binding Protein (VDBP) and Its Gene Polymorphisms-The Risk of Malignant Tumors and Other Diseases.

Vitamin D is an important component of the endocrine system that controls calcium homeostasis and bone mineralization. Because of the very short half-life of free serum vitamin D it is stabilized and transported to target tissues by being bound to the vitamin D binding protein (VDBP). The most common polymorphisms: rs4588 and rs7041 in the vitamin D binding protein gene may correlate with differences in vitamin D status in the serum. This review presents data that relate to the presence of genetic variants in the VDBP gene in correlation with certain diseases, mostly concerning cancers (breast, prostate, pancreatic, lung, colorectal, basal cell carcinoma cancer and cutaneous melanoma) or other related diseases (thyroid autoimmunity disorders, obesity, diabetes mellitus, bone metabolism, rheumatoid arthritis, ankylosing spondylitis, asthma, chronic obstructive pulmonary disease, tuberculosis and coronary artery diseases).

Assessment of vitamin D-binding protein (DBP) gene polymorphisms and their correlation with multiple sclerosis: a case-control study in a sample of the Syrian population

BackgroundVitamin D deficiency is a major health concern as it increases the risk of developing many serious diseases. Recently, the correlation between vitamin D deficiency and multiple sclerosis (MS) is a matter of serious debate. In this case-control study, we aimed to assess the correlation between genetic changes in the vitamin D-binding protein (DBP) gene and their consequence on MS patients. Our sample study consisted of 110 individuals; 40 patients with MS as cases and 70 healthy controls. Vitamin D levels were determined by immunofluorescence assay, and polymorphisms at rs7041 (c.1296 T > G p.Asp416Glu) and rs4588 (c.1307C > A p.Thr420Lys) of the DBP gene were genotyped using PCR/RFLP method for all cases and controls.ResultsOur results showed that genotype frequencies were consistent with Hardy-Weinberg equilibrium. A significant association was found in rs7041 (c.1296TT) homozygous wild-type, and the odds ratio was < 1 suggesting a protective role against developing MS (OR; 0.03, p = 0.0002) whereas the c.1296GG genotype was significantly correlated with an increased risk for MS by 6 folds (OR: 6.0000, p < 0.0001). No significant association was noted at rs4588 and MS occurrence. In addition, our compound genotyping results revealed that haplotypes 1S-1S are 6 times more likely to develop MS, whereas haplotypes 1F-1F had a more protective role in MS patients (OR: 0.063, p = 0.06.), respectively. The risk of vitamin D insufficiency in patients was greater by 14 folds compared to controls (OR: 14.05, p = 0.0128). Furthermore, the c.1296GG genotype was associated significantly by more than 4 times with insufficient levels of vitamin D and by 7 folds with vitamin deficiency.ConclusionsWe conclude that polymorphisms in the DBP gene could have independent effects on the risk of developing multiple sclerosis. The homozygous recessive genotype at rs7041 was associated with insufficient levels of vitamin D and with the risk of MS emergence.

Sputum Vitamin D Binding Protein (VDBP) GC1S/1S Genotype Predicts Airway Obstruction: A Prospective Study in Smokers with COPD.

IntroductionThe vitamin D binding protein (VDBP, also known as GC-globulin) and vitamin D deficiency have been associated with chronic obstructive pulmonary disease (COPD). rs7041 and rs4588 are two single nucleotide polymorphisms of the VDBP gene, including three common allelic variants (GC1S, GC1F and GC2). Previous studies primarily assessed the serum levels of vitamin D and VDBP in COPD. However, less is known regarding the impact of the local release of VDBP on COPD lung function. Thus, we examined the association of sputum and plasma VDBP with lung function at baseline and at four years, and examined potential genetic polymorphism interactions.MethodsThe baseline levels of sputum VDBP, plasma VDBP and plasma 25-OH vitamin D, as well as the GC rs4588 and rs7041 genotypes, were assessed in a 4-year Finnish follow-up cohort (n = 233) of non-smokers, and smokers with and without COPD. The associations between the VDBP levels and the longitudinal decline of lung function were further analysed.ResultsHigh frequencies of the haplotypes in rs7041/rs4588 were homozygous GC1S/1S (42.5%). Higher sputum VDBP levels in stage I and stage II COPD were observed only in carriers with GC1S/1S genotype when compared with non-smokers (p = 0.034 and p = 0.002, respectively). Genotype multivariate regression analysis indicated that the baseline sputum VDBP and FEV1/FVC ratio at baseline independently predicted FEV1% at follow-up.Discussion and ConclusionThe baseline sputum VDBP expression was elevated in smokers with COPD among individuals with the GC1S/1S genotype, and predicted follow-up airway obstruction. Our results suggest that the GC polymorphism should be considered when exploring the potential of VDBP as a biomarker for COPD.