ApaI Polymorphisms Research Articles

Influence of VDR gene polymorphisms on the development and course of breast cancer

Annotation. Breast cancer is the most common cancer diagnosed in women. In the last 5 years, it has been diagnosed in 7.8 million women, and in 2020, 685,000 deaths from breast cancer were registered. The growing number of patients with this pathology and the cost of therapy creates a need to study new methods of diagnosis and treatment. Therefore, detailed attention is paid to genetic risk factors for cancer, in particular, the VDR gene and its polymorphisms ApaI, TaqI, BsmI and FokI. Therefore, the purpose of this review is to collect and analyze currently known information about these SNPs and their relationship to the development, course and effectiveness of breast cancer treatment. To do this, an extensive literature review was conducted using basic databases, which described the effect of vitamin D3 on the tumor process and found that VDR receptor dysfunction increases the risk of breast cancer and affects the sensitivity of patients to treatment, which proves the effect of polymorphisms. ApaI, TaqI, BsmI and FokI on the development of pathology. Therefore, the prospects for further research are to study the prognostic value of each polymorphism and develop new treatments for the disease.

Estimation of vitamin D receptor gene polymorphism in Type 2 Diabetes Mellitus patients in Erbil city.

Type 2 diabetes mellitus (T2DM) is a global problem. Recent studies confirmed the association of genes and different single nucleotide polymorphisms with T2DM occurrence and progress. This study was aimed to estimate the vitamin D receptor (VDR) gene polymorphism in Type 2 Diabetes Mellitus patients in Erbil city. The results showed that the Body mass index (BMI), Systolic blood pressure and Diastolic blood pressure were significantly higher in the diabetic group compared to the control group (P<0.05). In addition, the percent of Glycated hemoglobin (HbA1c), Fasting blood glucose (FBG), and Homeostatic model assessment for insulin resistance (HOMA-IR) were significantly higher in the diabetic group compared to the control group (P<0.05). Among different parameters of lipid profile, only Low-density lipoprotein (LDL) was significantly higher in the diabetic group compared to the control group. It was found that FBG value was significantly higher in patients with GA and AA genotypes of BsmI compared with healthy controls. Patients with the GA genotype of BsmI had a higher value of triglyceride compared to healthy individuals. Patients with all ApaI genotypes had higher FBS values than controls. There were not observed any signi?cant associations among the BsmI and ApaI polymorphisms and the risk of T2DM. In conclusion, no evidence was found for the association between two VDR polymorphisms and T2DM patients in Erbil city.

Evaluation of vitamin D receptor gene polymorphisms in patients with differentiated thyroid carcinomas and nodular goiter.

The role of vitamin D has previously been determined in autoimmune and malignant thyroid diseases. We aimed to identify the haplotype distribution of single nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR) gene, which has been suggested to play a role in the pathogenesis of differentiated thyroid cancers and benign thyroid diseases. Two hundred and sixteen patients, 113 with benign and 103 with differentiated thyroid cancers, together with the same number of healthy controls, were included in the study. FokI, BsmI, ApaI, and TaqI SNPs in VDR were analyzed in all participants using the PCR-RFLP method. When the patients with differentiated thyroid cancers or the patients with nodular goiter and control cases were compared for BsmI, ApaI or TaqI polymorphisms, three genotype distributions (BB, Bb, bb; AA, Aa, aa; TT, Tt, tt) were found to not differ significantly. When the patients with differentiated thyroid cancers and control cases were compared for the FokI polymorphism in the VDR gene, the three genotype distributions (FF, Ff, ff) did not differ. However, in patients with nodular goiter, the FF genotype in the FokI polymorphism of the VDR gene was found to be statistically significantly higher (P=0.033). This is the first study in the literature evaluating the role of VDR gene SNPs in nodular goiter. We can suggest that SNP distribution in the VDR gene is not associated with malignancy but may cause some alterations in thyrocyte morphology and functions.

VDR polymorphisms effect on bone mineral density in Polish postmenopausal women.

Purpose: Osteoporosis is the most widespread systemic disease of the skeleton. According to estimated data for Poland, it affects ca. 3 million people. Although the disease is multifactorial, with significant influence of environmental factors on the increase of the risk of its occurrence, genetic factors play an important role in its pathogenesis. The aim of this study was an analysis of the relation of the ApaI, BsmI and TaqI polymorphisms of the VDR gene, with bone mineral density measured in lumbar spine and/or in proximal femur in a group of polish women. Methods: The study included 135 women at the postmenopausal age from the area of central Poland. BMD was measured at the hip and/or at the lumbar spine, using dual-energy X-ray absorptiometry. The influence of the selected VDR genotypes on bone mineral density was studied using the ApaI, the BsmI and the TaqI restriction enzymes. Lifestyle information was obtained via questionnaire. Results: Women with the 'bb' genotype showed lower BMD values of the hip (Total BMD value) comparing to patients with 'BB' or 'Bb' genotypes. We did not observe similar correlation for the lumbar spine. The remaining polymorphisms (ApaI and TaqI) did not demonstrate a significant relation with the differentiation of the mean BMD values obtained from the hip nor from lumbar vertebrae. Conclusion: The present study has demonstrated that the BsmI polymorphism of the vitamin D receptor gene is a factor of bone mineral density changes in postmenopausal women from Poland.

Polymorphisms of Vitamin D Receptor and the Effect on Metabolic and Endocrine Abnormalities in Polycystic Ovary Syndrome: A Review.

Polycystic ovary syndrome (PCOS) is one of the most prevalent endocrine disorder in women of reproductive age. Vitamin D and its receptor are thought to play an important role in PCOS susceptibility, although the impact of vitamin D receptor (VDR) polymorphisms on the hormonal and metabolic profile is still controversial. A literature search in PubMed and Embase was performed up to September 2020 for case-control studies in women suffering from PCOS, with outcome related to VDR polymorphisms effect on metabolic/endocrine disturbances. We have found 16 eligible studies including 2566 women with PCOS and 2430 controls. ApaI polymorphism seemed to be associated with hyperandrogenism in both Asian and Caucasian population. FokI variant was correlated with metabolic/endocrine parameters especially in Asian population, while a relation between Cdx2 genotypes and insulin sensitivity was observed in both ethnicities. VDR polymorphisms have an important role in PCOS development and related hormonal and metabolic abnormalities. Few case-control studies analysed the interaction between VDR variants and metabolic/endocrine parameters with the majority of the articles focused on the Asian region. Further research on various ethnic populations with larger sample size are still needed for a definitive conclusion, in order to allow early diagnosis and prevention of PCOS comorbidities.

The Significance of VDR Genetic Polymorphisms in the Etiology of Preeclampsia in Pregnant Polish Women.

For the first time in the Polish population, we aimed to investigate associations between the VDR gene single-nucleotide polymorphisms (SNPs) BsmI (rs15444410), ApaI (rs7975232), FokI (rs19735810), and TaqI (rs731236) and the development of preeclampsia (PE). A case–control study surveyed 122 preeclamptic and 184 normotensive pregnant women. The polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) method was performed to examine the maternal VDR FokI, BsmI, TaqI, and ApaI polymorphisms. The VDR BsmI AA homozygous genotype was statistically significantly more frequent in preeclamptic women compared to the control group (p = 0.0263), which was also associated with a 2-fold increased risk of PE (OR = 2.06, p = 0.012). A correlation between the VDR BsmI polymorphism with systolic and diastolic blood hypertension was noted. Furthermore, 3-marker haplotype CTA (TaqI/ApaI/BsmI) was associated with significantly higher systolic (p = 0.0075) and diastolic (p = 0.0072) blood pressure. Association and haplotype analysis indicated that the VDR BsmI A allele could play a significant role in the PE pathomechanism and hence could be a risk factor for PE development in pregnant Polish women. These results indicate the importance of the VDR BsmI polymorphism and reveal that this variant is closely associated with a higher predisposition to hypertension.

The VDR FokI (rs2228570) polymorphism is involved in Parkinson's disease

The etiology of Parkinson's disease (PD) is presumably multifactorial and likely involves interactions between genetic and environmental factors, as well as mitochondrial dysfunction, oxidative stress and inflammation. Among environmental factors, Vitamin D was reported to associate with the risk of PD. Vitamin D activity is mediated by its binding to the vitamin D Receptor (VDR), a transcriptional factor for almost 3% of human genes. We genotyped for ApaI, BsmI, TaqI, FokI and rs1989969 VDR single nucleotide polymorphisms (SNPs) a cohort of 406 PD and 800 healthy controls (HC) and found a strong association between the FokI (rs2228570) VDR SNP and PD. Thus, the TT genotype and the T allele resulted associated with PD in the overall analyzed PD population. Gender-based stratification of data indicated that results were maintained for FokI TT genotype and T allele in male PD patients, whereas the FokI T allele alone was confirmed as a risk factor for PD in females. Co-segregation analyses indicated the TaqI ApaI FokI rs1989969 GCTG as a “risk” haplotype for PD. In a subgroup of patients and controls neural Vitamin D and VDR concentration was analyzed in extravesicles (NDEVs) isolated from peripheral blood: no differences emerged between PD and HC. NDEVs results will need to be validated in ampler cohort but we can speculate that, if at neuronal level the amounts of Vitamin D and of VDR are comparable, than the bioavailability of vitamin D and the efficacy of the vitamin D/VDR axis is differentially modulated in PD by VDR SNPs.

Vitamin D Receptor Gene Polymorphisms in Childhood Brucellosis in Turkish Children

Abstract Objective The vitamin D receptor gene (VDR) polymorphisms and the risk of various infections have been studied. An association with brucellosis and vitamin D levels has been investigated but not yet with VDR gene polymorphisms. We aimed to examine the association between VDR gene polymorphisms and susceptibility to childhood brucellosis. Methods This case–control study included patients with brucellosis and healthy controls. After extracting genomic DNA using a Qiagen blood DNA isolation kit, five VDR single nucleotide polymorphisms (SNPs), including Cdx-2, FokI, BsmI, ApaI, and TaqI gene, were amplified. Genetic distribution of these SNPs of VDR gene in patient and control groups were compared. Results A total of 38 patients with brucellosis and 89 healthy controls were evaluated. The genotype distribution of Cdx2, FokI, BsmI, and ApaI polymorphisms were similar between patients and healthy controls. However, the CC homozygous genotype for VDR gene TaqI was significantly overexpressed in patients compared with controls (23.7 vs. 7.9%; p = 0.042). The frequency of the C allele of the TaqI genotype was significantly different between patients and controls (p = 0.018). On the other hand, presence of the A allele in the BsmI was associated considerably with an increased risk of brucellosis (p = 0.037). VDR polymorphism distribution was similar according to age, presence of complicated disease, and presence of bacteremia. The heterozygote TaqI polymorphism was more common in patients presented as subacute and chronic symptoms (p = 0.036). Conclusion Our results indicated the possible role in TaqI polymorphism of the VDR gene for the risk of brucellosis at the time of exposure to infection.

Evaluation of association studies and a systematic review and meta-analysis of VDR polymorphisms in type 2 diabetes mellitus risk.

Numerous original studies and 4 published meta-analyses have reported the association between the Vitamin D receptor (VDR) BsmI, FokI, ApaI, and TaqI polymorphisms and type 2 diabetes mellitus (T2DM) risk. However, the results were inconsistent. Therefore, an updated meta-analysis was performed to further explore these issues.To further explore the association between the VDR BsmI, FokI, ApaI, and TaqI polymorphisms and T2DM risk.PubMed, EMBASE, Scopus, and Wanfang databases were searched. The following search strategy were used: (VDR OR vitamin D receptor) AND (polymorphism OR variant OR mutation) AND (diabetes OR mellitus OR diabetes mellitus). Pooled crude odds ratios with 95% confidence intervals were applied to evaluate the strength of association in 5 genetic models. Statistical heterogeneity, the test of publication bias, and sensitivity analysis were carried out using the STATA software (Version 12.0). To evaluate the credibility of statistically significant associations, we applied the false-positive report probabilities (FPRP) and Bayesian false discovery probability (BFDP) test.Overall, the VDR BsmI polymorphism was associated with a significantly decreased T2DM risk in Asians; the VDR FokI polymorphism was associated with a significantly decreased T2DM risk in Asians, African countries, and Asian countries; the VDR ApaI polymorphism was associated with a significantly decreased T2DM risk in Caucasians and North American countries.On the VDR ApaI polymorphism, a significantly increased T2DM risk was found in a mixed population. However, when we further performed a sensitivity analysis, FPRP, and BFDP test, less-credible positive results were identified (all FPRP > 0.2 and BFDP > 0.8) in any significant association.In summary, this study strongly indicates that all significant associations were less credible positive results, rather than from true associations.

Polymorphisms of the Vitamin D Receptor Gene in Crohn’s Disease

Abstract Introduction Crohn’s disease (CD) and ulcerative colitis (UC) are chronic inflammatory conditions of the gastrointestinal tract. Studies have shown that polymorphisms of the vitamin D receptor (VDR) gene may help elucidate the pathogenesis of CD. Objectives To analyze the role of VDR gene polymorphisms (ApaI, BsmI, FokI, and TaqI) in the development of CD. Methods The present study is a systematic review with meta-analysis. a total of 50 articles in English and Portuguese published from 2000 to 2020 were selected from 3 databases. The relationship between CD and the VDR gene was addressed in 16 articles. Results The TaqI polymorphism was analyzed in 3,689 patients and 4,645 control subjects (odds ratio [OR] = 0.948; 95% confidence interval [95%CI] = 0.851–1.056; p = 0.3467). The ApaI polymorphism was studied in 3,406 patients and 4,415 control subjects (OR = 1,033; 95%CI = 0.854–1.250; p = 0.7356). For FokI polymorphism, there were 2,998 patients and 4,146 control subjects (OR = 0.965; 95%CI = 0.734–1.267; p = 0.7958). Lastly, the BsmI polymorphism was analyzed in 2,981 patients and 4,477 control subjects (OR = 1,272; 95%CI = 0.748–2.161; p = 0.3743). Conclusion These four VDR gene polymorphisms were not associated with CD. Therefore, further studies with larger samples are required to corroborate or rectify the conclusions from the present meta-analysis.

Are vitamin D deficiency and VDR gene polymorphisms associated with high blood pressure as defined by the ACC/AHA 2017 criteria in postmenopausal women?

ObjectivesTo 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 as defined by the 2017 ACC/AHA criteria. Study designA cross-sectional study of biobanked blood samples from 339 postmenopausal women. Main outcome measures: Blood pressure strata were defined according to the 2017 ACC/AHA cutoffs. Circulating 25(OH)D levels were considered deficient if <20 ng/mL. ResultsMean 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. A higher prevalence rate 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 associations lost significance when adjusted for age and BMI. ConclusionThe results suggest that vitamin D deficiency and Taq-I polymorphism are associated with stage 2 hypertension, depending on age and BMI, in postmenopausal women.

The role of TaqI, ApaI and BsmI polymorphisms of VDR gene in lumbar spine pathologies: systematic review and meta-analysis.

The objective of the present meta-analysis was to evaluate the association between TaqI (rs731236), ApaI (rs7975232) and BsmI (rs1544410) polymorphisms of the VDR gene and lumbar spine pathologies such as lumbar disc herniation and lumbar disc degeneration. VDR gene polymorphisms have been reported to be associated with an increased risk of lumbar spine pathologies. A systematic search was performed up to February 2020 using PubMed, EBSCO and Web of Science databases. We used the keywords and combinations "lumbar disc degeneration," "lumbar disc herniation," "lumbar spine pathologies" and "VDR polymorphism." Subsequently, we performed a meta-analysis with the results of the included studies. We found that the TaqI polymorphism was associated with an increased risk of developing lumbar spine pathologies (recessive model OR 1.25, 95% CI 1.01-1.54) and lumbar disc degeneration (allelic model OR 1.26, 95% CI 1.07-1.48; recessive model OR 1.34, 95% CI 1.06-1.69), but not with lumbar disc herniation. Additionally, ApaI was associated with an increased risk of developing lumbar spine pathologies (heterozygous model OR 1.45, 95% CI 1.06-1.98), but not with lumbar disc herniation or lumbar disc degeneration. Our findings indicate that TaqI and ApaI polymorphisms of the VDR gene are important risk factors for developing lumbar spine pathologies. Moreover, the TaqI polymorphism is a risk factor for lumbar disc degeneration.

Vitamin D receptor gene polymorphisms and risk of intervertebral disc degeneration: An updated meta-analysis based on 23 studies.

Background:Numerous studies have investigated the associations between Vitamin D receptor (VDR) gene polymorphisms and risk of intervertebral disc degeneration but the results remain controversial. This study aimed to drive a more precise estimation of association between VDR gene polymorphisms and risk of intervertebral disc degeneration.Methods:PubMed, EMBASE, Cochrane library, Web of Science and China Knowledge Resource Integrated Database for papers on VDR gene polymorphisms and risk of intervertebral disc degeneration were searched. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association in the homozygote model, heterozygote model, dominant model, recessive model and an additive model.Results:Overall, 23 articles were included in the final meta-analysis. The subgroup analyses by ethnicity showed a significant association of VDR FokI mutation with disc degeneration risk in Caucasians (recessive model, OR with 95%CI 1.301, [1.041, 1.626]; additive model, OR with 95%CI 1.119, [1.006, 1.245]). The results of subgroup analyses by ethnicity showed a significant association of VDR TaqI mutation with disc degeneration risk in Asians but not in Caucasians. There was a significant association between VDR ApaI mutation and risk of disc degeneration and subgroup analyses by ethnicity showed a significant association in Caucasians and in Asians.Conclusions:In summary, VDR FokI polymorphisms was associated with disc degeneration risk among Caucasians but not Asians, VDR TaqI polymorphisms was associated with disc degeneration risk among Asians but not Caucasians, while VDR ApaI polymorphism was associated with disc degeneration risk among Asians and Caucasians.

Association of vitamin D receptor polymorphisms with metabolic syndrome-related components: A cross-sectional study.

BackgroundThe association between vitamin D receptor (VDR) polymorphisms and metabolic syndrome (MS) has been demonstrated by epidemiological studies while their correlation remain controversial. The aim of this study is to investigate the association of VDR gene polymorphisms with MS and MS‐related components in the two communities of Hangzhou.MethodsA total of 394 subjects were enrolled in the cross‐sectional study. Four VDR gene polymorphisms (ApaI, BsmI, FokI, and TaqI) were selected based on human genome sequence databases and genotyped using the MassARRAY Analyzer Compact.ResultsIn lipid profile, the TT genotype of ApaI had a significantly lower risk of hypertriglyceridemia compared with the GG+GT genotypes (recessive model: OR = 0.141; 95% CI = 0.041–0.486; p < 0.01) and the GG genotype (codominant model: OR = 0.155; 95% CI = 0.044–0.545; p < 0.01). The levels of triglyceride (TG) in the TT genotype of ApaI were lower than the GG+GT genotypes (1.29 ± 0.63 vs. 1.78 ± 1.59 mmol/L, p < 0.01). Furthermore, the AA+GA carriers of BsmI had lower levels of high‐density lipoprotein cholesterol (HDL‐C) than the GG carriers (1.28 ± 0.29 vs. 1.42 ± 0.34 mmol/L, p < 0.05). The CC+TC carriers of TaqI also suffered from lower HDL‐C compared with the TT carriers (1.27 ± 0.29 vs. 1.42 ± 0.34 mmol/L, p < 0.01). For arterial blood pressure, the CC carriers had lower systolic blood pressure (SBP) than the TT+TC carriers (p < 0.01) and the TT carriers of FokI (p < 0.05). However, the FokI polymorphisms were not associated with SBP and the mean blood pressure of both groups laid within the normal range.ConclusionsIn our study, VDR polymorphisms show no association with the MS risk. The present results suggest that the VDR ApaI polymorphism is associated with hypertriglyceridemia and predisposed to developing MS, while the variants of BsmI and TaqI seem to affect HDL‐C. Nevertheless, the effect of FokI variants with SBP is ambiguous.

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.

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.

P164 Vitamin D receptor gene polymorphisms in a cohort of systemic lupus erythematosus patients in Malta

Abstract Background/Aims Vitamin D deficiency is highly prevalent in systemic lupus erythematosus (SLE) patients, most likely due to sun avoidance. Vitamin D acts through the vitamin D receptor (VDR) that is present in most cells, and it can regulate the transcription of over 200 genes. The expression of vitamin D receptors by a variety of cells belonging to the innate and adaptive immune systems has created interest with regards to the role of vitamin D in the pathogenesis of SLE. Several polymorphisms of the VDR gene have been described, namely Bsml (rs1544410), Apal (rs7975232), Taql(rs731236) and Fokl (rs2228570). A number of VDR gene polymorphisms have been associated with increased risk of SLE mostly in Asians and Africans. The aim of this study was to establish whether an association was present between VDR gene polymorphisms (Bsml, Apal, Taql and Fokl) and SLE susceptibility in a cohort of SLE patients living in Malta. Methods 63 SLE patients living in Malta and attending Rheumatology clinic at Mater Dei Hospital were recruited for the study after providing informed consent. The patients were over 18 years and fulfilled the SLICC classification criteria for SLE. Blood samples were taken from all the SLE patents. 93 cord blood samples obtained from individuals living in Malta were used as a control. DNA extraction was carried out from the blood samples. The VDR gene was screened and the regions containing the VDR polymorphisms were amplified for each patient. The amplified regions were then digested with their respective restriction enzymes in order to view the patient’s genotype via restriction fragment length polymorphism. Statistical analysis, including odds ratio (OR), was carried out to gauge the significance in the association of these polymorphisms with SLE. Results 93.7% of SLE patients were female and they had a mean age of 45.3 years. All the patients were of Caucasian ethnicity. 14.3% had vitamin D deficiency (serum 25-hydroxyvitamin D &amp;lt; 20ng/ml) and 25.4% were vitamin D insufficient (serum 25-hydroxyvitamin D 20-29ng/ml). The results showed that when Apa1 polymorphism was present as a homozygote for the variant allele (AA) there was a significant decrease in SLE prevalence (OR = 0.39, CI 0.17-0.87, p = 0.02). The results were also analysed by placing the polymorphs into haplotypes. The haplotype containing all wild-type alleles for the VDR gene and the haplotype containing all wild-type alleles with the variant allele for Fok1 had an increased prevalence of SLE by around 2 fold (OR = 1.95, CI 1.12-3.38, p = 0.01 and OR = 2.36, CI 1.13-4.91, p = 0.02 respectively). Conclusion The study showed that in the Maltese population the presence of the VDR gene polymorphism haplotype containing all wild-type alleles and the haplotype containing all wild-type alleles with the variant allele for Fok1 are associated with an increased risk of SLE. Disclosure J. Grech Meli: None. R. Magro: None. J. Debattista: None. N. Aquilina: None. K. Gatt: None. A.A. Borg: None. C. Scerri: None.

Association between vitamin D receptor polymorphisms and acute pancreatitis: A protocol for systematic review and meta analysis.

Background:Several studies have been performed to investigate the association between vitamin D receptor (VDR) gene polymorphism and acute pancreatitis, but the results are inconclusive. We conducted this meta-analysis for a precise estimation of the association between BsmI (rs1544410), ApaI (rs7975232), TaqI (rs731236), and FokI (rs2228570) polymorphisms and acute pancreatitis.Methods:Appropriate studies were retrieved by searching Web of Science, PubMed, Scopus, and Google scholar databases, until January 31, 2021. Two reviewers independently conducted data extraction and literature quality evaluation. Odds ratios and 95% confidence intervals were calculated to evaluate the strength of the association.All of the data were analyzed with Stata 16.0.Results:The results of this meta-analysis will be submitted to a peer-reviewed journal for publication.Conclusions:This meta-analysis will summarize the association between BsmI, ApaI, TaqI, and FokI polymorphisms and the risk of acute pancreatitis.Ethics and dissemination:Ethical approval was not required for this study. The systematic review will be published in a peer-reviewed journal, presented at conferences, and shared on social media platforms.OSF REGISTRATION NUMBER:DOI 10.17605/OSF.IO/83W7R.

The Most Common Vitamin D Receptor Polymorphisms (ApaI,FokI, TaqI, BsmI, and BglI) in Children with Dental Caries: A Systematic Review and Meta-Analysis

Vitamin D participates in the calcification of enamel and dentin and the appropriate immune responses to oral microbial infections. We aimed to assess the association between the most common vitamin D receptor (VDR) polymorphisms (ApaI, FokI, TaqI, BsmI, and BglI) and the risk of dental caries in children. Methods: PubMed/MEDLINE, Cochrane Library, Web of Science, and Scopus databases were comprehensively searched until 19 January 2021. Meta-analysis with odds ratios as the effect estimate along with 95% confidence intervals and subgroup analysis were conducted using Review Manager 5.3 software. Publication bias and sensitivity analyses were conducted by Comprehensive Meta-Analysis, version 2.0 software. Results: Seventy-eight studies were retrieved from the databases, with nine studies included in the final analysis. Based on five genetic models, there was no association between ApaI (rs7975232), TaqI (rs731236), BsmI (rs1544410), FokI (rs2228570), and BglI (rs739837) polymorphisms and susceptibility to dental caries, except for the FokI (rs10735810) polymorphism. Conclusion: Among the VDR polymorphisms considered, an association was found between the FokI (rs10735810) polymorphism and the risk of dental caries, with a protective role of the f allele and ff genotype.

Association of Vitamin D Receptor Gene Polymorphisms With the Evolution of MODY Diabetes: Study in Tunisian Patients.

Vitamin D (VD) cannot be considered as a true vitamin, but rather as a hormone, which exerts its action via a vitamin D receptor (VDR). Many genes have been shown to be involved in the evolution of diabetes in various populations, such as the vitamin D receptor gene. The aim of our study was to investigate if BsmI, TaqI, ApaI, FokI, and Tru9I, polymorphisms of VDR gene have an impact on MODY diabetes and its clinical aspects in a Tunisian population. A total of 95 patients and 153 controls were genotyped using PCR-RFLP. The comparison of the allelic and genotypic frequencies of the five polymorphisms between MODY subjects and control groups revealed the association of MODY diabetes with TaqI, Tru9I and BsmI polymorphisms and no significant differences were observed in the distributions for the ApaI and FokI polymorphisms. After stratification with biochemical and clinical parameters and TaqI, Tru9I and BsmI polymorphisms, we found an association between the three SNPs and different parameters such as age of diagnosis, therapy, hsCRP and HDL-C levels. Our results revealed that TaqI, Tru9I and BsmI polymorphisms may be more related to the progression of MODY diabetes. The possible role of vitamin D in the pathogenesis of MODY is far from being completely understood. Further knowledge on this issue may identify new candidate targets in the treatment and prevention of the disease. Our findings suggest that the TaqI, Tru9I and BsmI polymorphisms may be more related to the progression of MODY diabetes.