TaqI Genotypes Research Articles

Vitamin D receptor gene polymorphisms in multiple sclerosis disease: A case-control study

Abstract Multiple sclerosis (MS) is a common neurologic disorder that is a chronic inflammatory, demyelinating, and neurodegenerative disease of the central nervous system (CNS). Its etiology remains unknown. Several recent studies have found that decreased susceptibility to vitamin D deficiency is also associated with a decreased risk of MS. The role of vitamin D receptor (VDR) gene and its polymorphisms are highlighted as susceptible components. In this study, we aimed to identify the relationship between ApaI (rs7975232), BsmI (rs 1544410), and TaqI (rs731236) gene polymorphisms with MS. ApaI, BsmI, and TaqI genotypes were determined in 70 patients with MS and in 70 control subjects. DNA was isolated from blood samples, and then ApaI, BsmI and TaqI gene polymorphisms were identified using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. The distribution of BsmI and TaqI polymorphisms did not show any significant differences in MS patients and controls; however, increased A allele of ApaI polymorphism was found in MS patients. Our findings suggest that the ApaI gene polymorphism might be associated with MS. Investigation of a larger population and functional work on these gene structures and function in MS patients are recommended.

The association between vitamin D receptor gene polymorphisms and hepato-cellular carcinoma in Egyptian patients with chronic liver disease

AimTo evaluate the possible association between vitamin D receptor single nucleotide polymorphisms and hepato cellular carcinoma in Egyptian patients with chronic liver disease. MethodSpecific primer sequences of the vitamin D receptor gene rs1544410, rs7975232, and rs731236 were used to detect vitamin D receptor polymorphisms in blood sample by polymerase chain reaction restriction fragment polymorphism. Allele specific restriction enzymes BsmI, ApaI and TaqI were used to digested PCR amplified products and the bands of specific PCR-RFLP fragments were resolved by 2% Ethidium bromide agrose gel electrophoresis. Genotypes and alleles were identified by their specific banding pattern on the gel electrophoresis via ultraviolet illumination. ResultThe frequencies of the 3 single nucleotide polymorphisms BsmI, ApaI, and TaqI genotype and the haplotype distribution were similar in patients with chronic liver disease either with or without hepato-cellular carcinoma. Neither of vitamin D receptor gene polymorphisms were a risk or protective factor for HCC; nor did these polymorphisms alter the risk for HCC development by coexisting HCC with chronic hepatitis C virus infection. TaqI polymorphism was associated with increased risk of progression of chronic liver disease to liver cell failure and decompensated liver disease. Conclusionvitamin D receptor single nucleotide polymorphisms at BsmI, ApaI, and TaqI did not provide significant association with HCC cancer risk or protection in the overall analysis in Egyptian population with chronic liver disease.

Vitamin D Receptor TaqI Polymorphism Is Associated With Reduced Follicle Number in Women Utilizing Assisted Reproductive Technologies.

Calcitriol, or 1,25-hydroxycholecalciferol, is the active form of vitamin D. It binds and activates vitamin D receptor (VDR). Infertility and defective folliculogenesis have been observed in female vdr-knockout mice; however, whether VDR polymorphisms affect human ovarian responses to controlled ovarian stimulation (COS) remains unclear. We hypothesized that VDR polymorphisms are associated with infertility and COS responses. Thus, we evaluated the association between the TaqI, BsmI, and FokI VDR polymorphisms and ovarian responses in women undergoing COS. In this study, we recruited a control group (n = 121) comprising volunteers with a history of natural conception and a second group of women undergoing COS (n = 70). TaqI, BsmI, and FokI genotyping was performed via restriction fragment length polymorphism analysis or TaqMan qPCR and Sanger sequencing. Intrafollicular 25(OH)D contents were measured in follicular fluid collected from COS patients during oocyte retrieval. Ovarian response parameters were obtained from patient medical records. There were no significant differences in the genotype frequencies of VDR polymorphisms (TaqI, BsmI and FokI) between the control and COS groups. However, the allele frequency of TaqI (C allele) was significantly lower in the COS group than in the control group (p = 0.02). Follicle number but not oocyte number was lower in patients with TaqI polymorphic (TC/CC) genotypes (p = 0.03). Importantly, the ratio between the number of follicles retrieved and intrafollicular estradiol concentrations was higher in patients with the TC/CC TaqI genotypes (p < 0.02). We identified an association between the VDR TaqI polymorphism and reduced follicle number in women undergoing COS, suggesting that VDR signaling affects the ovarian response to stimulation via unknown mechanisms.

Relationship between vitamin D receptor gene polymorphism and susceptibility to chronic kidney disease and periodontal disease in community-dwelling elderly.

The aim of this study was to investigate the possible correlation between vitamin D receptor (VDR) gene polymorphism and susceptibility to chronic kidney disease (CKD) and periodontal disease. This study analysed 345 participants, who were all 79years of age. Kidney function levels were determined based on the estimated glomerular filtration rate (eGFR; non-reduced function: ≥60 and reduced function: <60mlmin-1 1.73m-2 ). VDR TaqI genotyping was also studied. We calculated the periodontal inflamed surface area (PISA). After classifying participants into quartile groups according to eGFR or PISA values, the subjects were then split into two groups (highest quartile versus the other three groups combined). Multiple logistic regression analysis was performed to evaluate the odds ratios between the eGFR and VDR TaqI genotype with the different PISA groups. The eGFR was set as the dependent variable while the VDR TaqI genotype, HbA1C, gender, smoking habits and body mass index were defined as independent variables. A significant association was observed between the VDR TaqI genotype and eGFR in the PISA high group (odds ratio=3.97, p=.027). Study results suggest that VDR TaqI genotype might be associated with CKD during inflammatory conditions caused by periodontal disease.

Vitamin D receptor gene TaqI single nucleotide polymorphism is not associated with lead levels in maternal and umbilical cord blood

Purpose: We aimed to investigate the association of vitamin D receptor (VDR) gene TaqI single nucleotide polymorphism (SNPs) with serum lead (Pb) levels in maternal and umbilical cord blood.Materials and methods: Eighty-one patients who lived in Konya, Turkey for the last 3 years and had delivery at Başkent University Konya Hospital in 2016 were included in this study. Venous blood samples were drawn from each volunteer immediately before giving birth to determine the maternal Pb levels and VDR SNPs. Additionally, umbilical cord blood samples were collected from the umbilical vein into tube with EDTA as an anticoagulant immediately after birth to determine Pb levels of the fetus.Results: The median level of Pb in the maternal blood was 29.00 (Interquartile Range (IQR) = 16.35) μg/L and the median Pb level in the cord blood was 22.50 (IQR = 9.75) μg/L. Blood Pb level of women living in the urban area was significantly higher than in those living in the rural area (Z = 2.118; p = .034). There was a very strong positive correlation between the Pb levels in the maternal blood and in the umbilical cord blood (ρ = 0.825, p < .001, respectively). Regarding VDR SNPs, “TT”, “TC”, and “CC” VDR TaqI genotypes were observed in 28 (34.6%), 45 (55.5%), and eight samples (9.9%), respectively. Pb levels in maternal and cord blood were higher in women with the “CC” VDR TaqI genotype; however, there was no statistically significant difference (p > .05).Conclusions: Although women with the “CC” VDR TaqI genotype had higher maternal and cord blood Pb levels, this was statistically insignificant and therefore, VDR TaqI SNPs did not significantly affect maternal and umbilical cord blood Pb levels.

Vitamin D receptor gene polymorphisms as a risk factor for obesity in Saudi men.

BackgroundThe prevalence of obesity and vitamin D deficiency in Saudi Arabia has increased recently. Decreased physical activity might play a role in obesity. Previous studies showed an association between low vitamin D level and its receptor polymorphism with obesity development.ObjectiveTo determine association of low vitamin D level and its receptor polymorphism with obesity in Saudi men.MethodsThis case control study was carried out from March 2016 through March 2017. Three hundred Saudi male students (from applied medical sciences in Taif University, Taif, Saudi Arabia) were classified according to BMI into lean, overweight and obese groups. For each individual, blood glucose, cholesterol, HDL-C, LDL-C, insulin and 25-(OH) vitamin D were measured. In addition, Apal, BsmI and TaqI genotypes were performed for each individual from March 2016 through March 2017, through computer-based search of the following databases: PubMed, Web of Science (Thomson ReutersTM). The references of the original literature and the related articles were also searched, for potential complementary studies. Data were analyzed by SPSS version 16, using Spearman’s rho and ANOVA tests.ResultsThere was significant negative association between 25-(OH) vitamin D level and obesity (p<0.01). Genotyping study showed that both bb of BsmI and tt of TaqI genotypes were higher in the obese group compared with lean group (p<0.05). Moreover, bb genotype has higher BMI and HOMA-IR than both BB and Bb; and tt genotype also has higher BMI and HOMA-IR than TT and Tt genotypes (p<0.05).ConclusionLow vitamin D level and VDR BsmI and Taq1 genotypes may be a risk factor of obesity.

Vitamin D status, serum lipid concentrations, and vitamin D receptor (VDR) gene polymorphisms in Familial Mediterranean fever.

Vitamin D (VitD) is critical for the regulation of inflammatory processes, and VitD deficiency has been linked to several chronic inflammatory disorders. We aimed to investigate the concentrations of serum 25(OH)D3, lipid parameters, and three known VDR polymorphisms (BsmI, FokI, and TaqI) in patients with Familial Mediterranean fever (FMF), an autosomal recessive autoinflammatory disease. The study included 123 FMF patients and 105 controls. Seventy patients had no attack (group 1), 30 had 1-2 attacks (group 2), and 23 had 3 or more attacks (group 3) within last three months. Serum 25(OH)D3 concentrations were determined using liquid chromatography-tandem mass spectrometry. BsmI, FokI, and TaqI polymorphisms were analyzed by a competitive allele specific polymerase chain reaction assay (KASPar). Serum lipid parameters were measured with enzymatic colorimetric methods. 25(OH)D3 concentrations were lower in FMF patients compared to controls (p < 0.001). No difference was observed in 25(OH)D3 concentration between groups 1, 2, and 3. The distributions of FokI and TaqI genotypes were not significantly different between FMF patients and controls. There was a significant difference in the distribution of AA BsmI genotype between male FMF patients and male controls. Increased concentrations of triglycerides (p = 0.012) and decreased concentrations of high-density lipoprotein cholesterol [HDL-C] (p = 0.006) were found in FMF patients compared to controls. Although lower 25(OH)D3 concentrations were observed in FMF patients versus controls, no association was determined between FMF attack frequency and 25(OH)D3 concentrations. We showed that the AA genotype of BsmI polymorphism is associated with FMF in males but not in females. The effects of decreased HDL-C and increased triglyceride concentrations on cardiovascular events in FMF patients should be further investigated.

Vitamin D receptor gene polymorphisms and the risk of multiple sclerosis: An updated meta-analysis

BackgroundThe association between vitamin D receptor (VDR) gene polymorphisms and multiple sclerosis (MS) has been extensively studied, but results were controversial. MethodsThis meta-analysis aimed to confirm whether VDR gene polymorphisms were associated with MS. Meta-analysis on the association between MS and VDR ApaI, BsmI, TaqI and FokI polymorphisms were conducted using allelic contrast, recessive, homozygotes and dominant models. Data were extracted by standardized forms and odds ratios (OR) with 95% confidence intervals (CI) were calculated using the random effects model if the results were heterogeneous. Stratification analysis by the selected study characteristics were performed to detect potential source of heterogeneity. ResultsA total of 21 relevant studies involving 3593 MS patients and 3917 controls were included in the analysis. The association between TaqI polymorphism and MS risk was significant in the homozygous model (p = 0.006) indicated a significant protective effect of TT TaqI genotype. High latitude (40.1–50°N) was also found markedly influenced TaqI polymorphism and MS risk in the recessive and homozygous models (p = 0.045 and p = 0.015, respectively). Additionally, Asian or low latitude (20.1–30°N) people with ApaI homozygous genotype, ‘> 2013’ publication year people in the allele contrast and dominant models of FokI, ‘> 40 years’ age people with BsmI recessive model also indirectly significantly affected the association between VDR gene polymorphisms and MS risk. ConclusionTaqI polymorphism is a significant protective factor for MS. However, the associations between ApaI, FokI and BsmI polymorphisms and MS were found only by study characteristics.

Association between Serum 25-hydroxy Vitamin D Concentration and TaqI Vitamin D Receptor Gene Polymorphism among Jordanian Females with Breast Cancer.

Background:Breast cancer is the most common type of cancer among females. Genetic polymorphisms might have a role in carcinogenesis. The aim of this study was to determine whether C to T base substitution within TaqI Vitamin D receptor (VDR) gene (rs731236) in exon 9 was a risk factor among patients with breast cancer.Methods:Peripheral blood was drawn from 122 Jordanian breast cancer patients and 100 healthy Jordanian volunteers in Al-Basheer Hospital during the summer months (from June to November of 2013, 2014, and 2015). DNA was amplified using polymerase chain reaction (PCR), followed by TaqI restriction enzyme digestion. Quantification of serum 25-hydroxy Vitamin D (25[OH]D) level was determined by competitive immunoassay Elecsys.Results:Genotypic frequencies for TaqI TT, Tt, and tt genotypes were 41%, 46%, and 13% for breast cancer compared to 42%, 50%, and 8% for control, respectively. Vitamin D serum level was significantly lower in the breast cancer patients (8.1 ± 0.3 ng/ml) compared to the control group (21.2 ± 0.6 ng/ml; P = 0.001). This study showed an inverse association between 25(OH)D serum level and breast cancer risk (odds ratio [OR], 22.72, 95% confidence interval [CI], 10.06–51.29).Conclusions:An inverse association was found between 25(OH)D serum level and breast cancer risk. Statistical difference was also found between different VDR TaqI genotypes and circulating levels of 25(OH)D among Jordanian females with breast cancer.

Vitamin D Receptor Polymorphisms of ApaI (rs7975232) and TaqI (rs731236) in South Indian Postmenopausal Osteoporotic and Healthy Women

Two adjacent single nucleotide polymorphisms of the vitamin D receptor gene (VDR) ApaI (rs7975232) and TaqI (rs731236) are commonly studied in several pathologies. We aimed to evaluate the distribution of VDR ApaI, and TaqI allele and genotype frequencies in 50 cases of postmenopausal osteoporotic (cases) and 50 postmenopausal healthy women (controls). The polymorphisms were detected using PCR RFLP. ApaI (rs7975232) polymorphism genotype frequencies were AA 68.08%, Aa 25.53% and aa 6.38% in postmenopausal osteoporotic women and AA 38.00%, Aa 46.00% and aa 16.00% in postmenopausal healthy controls respectively (?2 = 8.96, p = 0.011). Taq l (rs731236) polymorphism genotype frequencies were TT 40.00%, Tt 56.00% and tt 4.00% postmenopausal osteoporotic women and TT 4.00%, Tt 64.00% and tt 32.00% in postmenopausal healthy women (?2 = 25.88, p = 0.000002). The Odds ratio for ApaI (rs7975232) polymorphism was 2.8148 with 95 % CI: 1.1207to7.0696 and a significance level p = 0.0276 and for TaqI (rs731236) polymorphism was 3.7778 with 95 % CI: 1.6496to8.6514 and a significance level p = 0.0017. Our study confirmed that the odds of getting osteoporosis were 2.8 fold greater when the A allele is inherited for ApaI (rs7975232) polymorphism and 3.7 fold greater when the T allele is inherited for TaqI (rs731236). In conclusion our study has proved to a certain extent that the VDR gene polymorphisms ApaI (rs7975232) and TaqI (rs731236) might be important genetic markers in determining postmenopausal risk of osteoporosis in a population of south Indian women.

Relationship among methadone dose, polymorphisms of dopamine D2 receptor and tri-dimensional personality questionnaire in heroin-addicted patients.

BackgroundWe investigated whether variation in the dopamine D2 receptor gene (DRD2) and tri-dimensional personality questionnaire (TPQ) scores could be used to aid adjustment of daily methadone requirements of heroin addicts. DRD2 TaqI B polymorphisms and TPQ scores were determined in 138 male Taiwanese heroin addicts who were receiving methadone treatment. Borderline index (harm avoidance + novelty seeking—reward dependence) was calculated for each subject, and three groups were defined: high (mean from all subjects plus 1 standard deviation, or greater), low (half of the calculated high score, or lower) and medium (all values between the high and low scores).ResultsNo significant differences in age (p = 0.60), mean methadone dose (p = 0.75) or borderline index group (p = 0.25) were observed between subjects bearing the B1/B1, B1/B2 and B2/B2 DRD2 TaqI genotypes. Among the individuals with low (≤10), medium (11–20) and high (≥21) borderline index scores, there was a significant difference in mean methadone dose (p = 0.04), but not age (p = 0.90). Further analysis showed that mean methadone dose was significantly higher in subjects with low borderline index scores than in those with high scores (62.5 vs. 47.0 mg/day, p = 0.03). The odds ratio for a daily methadone requirement ≥60 mg (median dose across the 138 subjects) was 2.64-fold greater in the low borderline index group than in the high group (p = 0.04).ConclusionsAlthough the DRD2 TaqI B genotype was not associated with methadone use requirements, borderline index was revealed as a potential predictive marker for the adjustment of methadone dosage requirements in heroin addicts.

Vitamin D Receptor Gene Polymorphism in Egyptian Patients with Knee Osteoarthritis

Introduction : Several polymorphisms have been implicated and associated with osteoarthritis (OA), including vitamin D receptor (VDR). VDR is present in many tissues, including chondrocytes. Vitamin D has been found to increase synthesis of proteoglycan in vitro , suggesting that it may affect the cartilage metabolism. Objective: to investigate the frequency of the VDR gene polymorphism in Egyptian patients with knee OA, and compared them with controls. Subjects and Methods : 200 patients with primary knee OA according to the American College of Rheumatology criteria and 200 matched controls who had no OA. Clinical impact of OA were assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire. VDR gene polymorphism Bsm I, Apa I, FokI and Taq I restriction fragment length polymorphisms (RFLPs) were determined by the polymerase chain reaction (PCR). Results : The frequency of ApaI genotype and alleles did not differ significantly between the knee OA patients and the controls. However, three genotypes where significantly higher in knee OA patients than in controls: the bb genotype of BsmI, TT genotype of TaqI and FF genotype of FokI. Knee OA patients with osteophytes had significantly more frequent bb genotype of BsmI, TT genotype of TaqI and FF genotype of FokI. BsmI, TaqI and FokI genotypes or alleles did not show any association with the presence of joint space narrowing (JSN). Knee OA patients who had bb genotype of BsmI, TT genotype of TaqI and FF genotype of FokI are associated with significantly higher WOMAC scores. Conclusion : The current study suggests that VDR gene polymorphism may be associated knee OA in the studied group of Egyptian patients. Association was mostly with severe clinical manifestation and osteophyte formation but not with JSN.

Associations of vitamin D deficiency and vitamin D receptor (Cdx-2, Fok I, Bsm I and Taq I) polymorphisms with the risk of primary open-angle glaucoma

BackgroundVitamin D deficiency and vitamin D receptor gene polymorphisms are known to be significantly associated with high myopia. Whether this genetic variant may impact primary open-angle glaucoma is largely unknown. This study investigated whether vitamin D receptor gene polymorphisms are altered in primary open-angle glaucoma subjects carrying the risk allele, and whether vitamin D deficiency is an important factor in the development of glaucoma.MethodsSeventy-three POAG patients and 71 age-matched controls from the Han population were enrolled. Serum levels of 1a, 25-Dihydroxyvitamin D3 were measured by enzyme-linked immunoabsorbent assay. Vitamin D receptor polymorphisms (Cdx-2, Fok I, Bsm I and Taq I) were analyzed using real-time polymerase-chain reaction high resolution melting analysis.ResultsSerum levels of 1a, 25-Dihydroxyvitamin in primary open-angle glaucoma patients were lower than in age-matched controls. Statistical analysis revealed a significant difference in the allelic frequencies of the BsmI and TaqI genotypes between primary open-angle glaucoma patients and age-matched controls, while other polymorphisms did not show any significant differences.ConclusionsVitamin D deficiency and the presence of the BsmI ‘B’ allele and the TaqI ‘t’ allele are relevant risk factors in the development of glaucoma.Trial registrationClinical Trials.gov: NCT02539745.The study was registered retrospectively on August 3rd, 2015. The first participant was enrolled on July 4th, 2013.

The Role of Vitamin D Receptor Polymorphisms on Dental Caries.

To determine the association between the ApaI, FokI, Cdx2 and TaqI polymorphisms of vitamin D receptor (VDR) gene in caries-active (high-moderate) and caries-free children. A hundred and fifty children (75 males, 75 females, mean age: 10.19 ± 1.61 years) were included in the study. The subjects were divided into three groups as high caries risk group (DMFT, dft>4)(n=55), moderate caries risk group (DMFT, dft=1-4)(n=57) and caries-free group (n=38). From each individual, blood samples were collected and DNA was extracted. The VDR gene was genotyped for the polymorphisms ApaI, FokI, Cdx2 and TaqI using polymerase chain reaction and restriction fragment length polymorphism methods. All data were analyzed by chi-square test, Fisher's exact test and t test. There was statistically significant difference in the frequency of TaqI genotypes (tt) between caries-active and caries-free children (p=0.029). No statistically significant differences were detected between ApaI, FokI, Cdx2 genotypes and dental caries. In the future, VDR gene polymorphisms may be used as a marker for the identification of patients with high caries risk.

Abstract B39: Effect modifiers of vitamin D receptor common polymorphisms on prostate cancer risk

Abstract Background: Studies have long proposed the influence of vitamin D and the vitamin D receptor (VDR) on prostate cancer (PCa) initiation and progression, however few studies support the association of VDR variants with PCa. The VDR is a transcription factor which binds to vitamin D and influences the expression of many genes implicated in Pca. Given the complexity of vitamin D availability, we hypothesized that the associations of VDR single-nucleotide polymorphisms (SNPs) with PCa can be modified by various behavioral and biological factors. In this study, we examined VDR SNPs and PCa risk and aggressiveness in African Americans (AAs) and European Americans (EAs) and determined if the associations were modified by behavioral and biological factors that influence serum vitamin D levels, including vitamin D and calcium intake, tobacco use, body mass index (BMI), skin pigmentation, and ultraviolet radiation exposure. Methods: The total of 810 AAs and 487 EAs from Chicago, IL and Washington, D.C. were included. Seven SNPs in and around the VDR gene and 105 ancestry informative markers were genotyped. We performed logistic regression analyses adjusting for relevant variables. Results: In EAs, TaqI (rs73136) and BsmI (rs1544410) minor alleles (respectively C and A allele) revealed a protective effect against PCa, while BsmI AA genotype showed increased odds of having high grade PCa (Gleason Score ≥4+3) in AAs with OR=2.67 (95% C.I.: 1.01-7.11). We also observed evidence of interactions between VDR SNPs and behavioral and biological factors that modify serum vitamin D levels. The TaqI C allele increased odds of PCa in AAs with behavioral and biological factors that reduce serum vitamin D levels, such as low vitamin D intake, current or past tobacco use, and darker skin pigmentation. Among AA men with vitamin D intake &amp;lt;400 IU/day, the TaqI CT/CC genotype significantly increased odds of PCa (P=0.007, OR=1.79, 95% C.I.: 1.17-2.75), but not AA men with high vitamin intake (≥400 IU/day). The interaction between TaqI genotypes and vitamin D intake was significant (P=0.01). The TaqI CT/CC genotype significantly increased odds of PCa among AA men who have smoked or with darker skin pigmentation (P&amp;lt;0.05), but not among AA men who never smoked or with lighter skin pigmentation. On the other hand, the TaqI C allele reduced odds of PCa among EA men with biological factors that decrease serum vitamin D levels. The TaqI CT/CC genotype significantly reduced odds of PCa among obese (BMI≥30) or darker pigmented men (P&amp;lt;0.05), but not among lean or lighter pigmented men. The interaction between BMI and TaqI genotypes in EA men was significant (P=0.05). Conclusion: Although a larger sample size is necessary to confirm our observations, our results suggest that the VDR gene is involved in PCa pathogenesis and progression, but the effects of VDR gene on PCa are modified by behavioral and biological factors that modify serum vitamin D levels. Citation Format: Ken Batai, Adam B. Murphy, Ebony Shah, Rick A. Kittles. Effect modifiers of vitamin D receptor common polymorphisms on prostate cancer risk. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr B39.

Association between vitamin D receptor ApaI and TaqI gene polymorphisms and gestational diabetes mellitus in an Iranian pregnant women population

It has been proposed that variants of the nuclear vitamin D receptor (VDR) gene are associated with a susceptibility to type 2 diabetes mellitus (T2DM) and gestational diabetes mellitus (GDM). Our study was aimed to evaluate a possible association between the VDR ApaI (rs7975232) and TaqI (rs731236) gene polymorphisms and susceptibility to GDM in an Iranian pregnant women population. This case–control study was performed on a population of pregnant Iranian women, including 157 GDM and 157 non-GDM subjects.VDR ApaI and TaqI polymorphisms were assessed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).Our finding showed that the genotypes frequency of VDR ApaI polymorphism was significantly different between GDM and non-GDM groups (χ2=8.5, P=0.014). The CC genotype increased the risk of GDM as compared to the AA genotype (AA vs.CC, OR=2.996, 95% CI=1.278–7.022, P=0.012). The genotype and allele frequencies of VDR TaqI polymorphism were significantly different between GDM and non-GDM subjects (χ2=7.27, P=0.026, χ2=4.08, P=0.043 respectively). A significant protection was shown against GDM in VDR TaqI genotypes and allele (TT vs.TC, OR=0.523, 95% CI=0.23–0.84, P=0.007, TT vs. TC+CC, OR=0.546, 95% CI=0.35–0.86, P=0.009, T vs. C, OR=0.711, 95% CI=0.511–0.99, P=0.043). In conclusion, our findings show a significant association between VDR ApaI and TaqI gene polymorphisms and the GDM at the investigated loci.

Association Between Vitamin D Receptor Polymorphism and Familial Mediterranean Fever Disease in Turkish Children.

Familial Mediterranean fever (FMF) is an autosomal recessive, inherited autoinflammatory disease characterized by recurrent, self-limited attacks of fever, and inflammation of serosal surfaces. The aim of our study was to determine a possible relationship between Vitamin D receptor (VDR) gene polymorphisms and the risk of children with FMF. We investigated VDR FokI (rs10735810), TaqI (rs731236), BsmI (rs1544410), and ApaI (rs7975232) polymorphisms in 50 children with FMF and 150 age-matched healthy control subjects. This study was performed by polymerase chain reaction-based restriction fragment length polymorphism. There was no significant difference between patients and controls for VDR FokI, TaqI, BsmI, and ApaI genotypes and alleles (p > 0.05). Results need to be supported by further investigations that define haplotype patterns for VDR gene polymorphisms in a larger group and different ethnic groups of FMF patients.

The Effect of Some Polymorphisms in Vitamin D Receptor Gene in Menopausal Women with Osteoporosis.

Vitamin D receptor gene is one of candidate genes related to osteoporosis expansion. The association of ApaI, TaqI, BsmI polymorphisms in vitamin D receptor gene with bone metabolism and density has been area of interest in many studies. This study was conducted to further investigate the association between the ApaI, TaqI, BsmI polymorphisms and bone density. This study was analytical study. Centers for bone density measurement in southwestern Iran. In this analytical study, 200 participants aged 45- and above 45-year-old women referring the centers of bone density measurement participated. The bone density of femoral neck and lumbar vertebrae was measured using dual-energy X-ray absorptiometry method. Based on t-score, the participants were assigned into patients (n=130) and healthy individuals (n=70). Different genotypes of ApaI (AA/Aa/aa), TaqI (TT/Tt/tt), and BsmI (BB/Bb/bb) were determined by PCR-RFLP. The data on bone density and PCR-RFLP were analysed by chi-square and ANOVA. Also, triad combination of the genotypes was statistically analysed. For each genotype combination, chi-square was run between the patients and control group and p-value was calculated. No significant association was seen between ApaI polymorphism and bone density (p>0.05). TaqI and BsmI polymorphisms had a significant association with femoral neck's bone density (p<0.05), but these polymorphisms were not significantly associated with lumbar vertebrae's (p>0.05). Patients with homozygous dominant TT genotype had the least bone density in femoral neck compared to other genotypes. Lumbar vertebrae's bone density was similar in three TaqI genotypes. The patients with homozygous recessive bb genotype had the least bone density in femoral neck and lumbar vertebrae compared to other genotypes. TaqI and BsmI polymorphisms could be desirable markers in diagnosis of women at risk of osteoporosis in the studied region in Iran. Therefore, these women will receive suitable medical treatment at proper time.

TaqI, FokI, and ApaI Polymorphisms in the Vitamin D Receptor in Behçet's Disease in Turkish Population.

Objectives. In our study we aimed to determine VDR gene polymorphisms in patients with Behçet's disease (BD) and neuro-Behçet's disease (NBD) in Turkish population. Methods. PBL obtained from 37 patients with BD, 21 patients with NB, and 30 healthy controls were investigated. Genomic DNA was extracted from whole blood using the QIAamp Blood Kit. VDR ApaI (rs7975232), VDR FokI (rs2228570), and VDR TaqI (rs731236) genotyping was performed by real-time polymerase chain reaction with SimpleProbe melting-curve analysis. Results. The allelic and genotype distributions of FokI and TaqI polymorphisms were not different among Behçet's disease, neuro-Behçet's disease, and control subjects in Turkish population (p > 0.05). Only the frequency of ApaI A allele in control is higher than that in BD (60% versus 38.5%), and the p value is 0.014, but the power is not enough to conclude that ApaI A allele is protective in BD in our study. Taken together, we found no significant differences between the BD, NBD, and control groups regarding the distribution of ApaI, TaqI, and FokI genotype and alleles frequencies. Conclusions. Future studies with larger patients' numbers may show differences between VDR polymorphisms and Behçet's disease.

The relationship between vitamin D receptor (VDR) polymorphism and the occurrence of osteoporosis in menopausal Iranian women

Osteoporosis, a multifactorial disease with reduced bone mineral density which increases the probability of bone fractures, is caused by calcium deficiency, and its incidence increases with age. It has been determined that mutations in functional regions of vitamin D receptor gene will affect the metabolism of minerals especially calcium and, therefore, bone density. The present study evaluates the relation between vitamin D receptor polymorphisms, TaqI (rs731236) and ApaI (rs7975232), and osteoporosis in menopausal Azari women in Zanjan province. This case-control study has been conducted on 50 menopausal women suffering from osteoporosis and 50 menopausal women who did not suffer from osteoporosis in Zanjan province. The diagnosis of osteoporosis was confirmed using DEXA instrument. Peripheral blood was collected from the subjects and controls to extract DNA and assess the ApaI and TaqI polymorphisms using PCR-RFLP method. The results were interpreted using independent T-test, chi-square, and Pearson correlation coefficient with a p-value less than 0.05. There was not a significant difference between the frequency of ApaI (AA/Aa/aa) and TaqI (TT/Tt/tt) genotypes in cases (mean age 68.72) and controls (mean age 64.7) (p=0.37 and p=0.64, respectively). In addition, ApaI/TaqI allele haplotype in osteoporotic population showed non-significant relation (p value=0.563) compared with the control group. The relationship between the genotypes and osteoporosis, cancers, and mineral metabolism disorders has been studied for a long time. Although there has been a significant relation between the aforementioned genotypes and osteoporosis or reduced mineral density-related bone fractures in some studied, some other studies have opposing results. Therefore, it is only possible to reach an acceptable conclusion by studying the haplotype of the polymorphisms in subjects.