TaqI Genotypes Research Articles

Exploring the Influence of VDR Genetic Variants TaqI, ApaI, and FokI on COVID-19 Severity and Long-COVID-19 Symptoms.

There is increasing evidence regarding the importance of vitamin D in the prognosis of coronavirus disease 2019 (COVID-19). Genetic variants in the vitamin D receptor (VDR) gene affect the response to vitamin D and have been linked to various diseases. This study investigated the associations of the major VDR genetic variants ApaI, FokI, and TaqI with the severity and long post-infection symptoms of COVID-19. In total, 100 Jordanian patients with confirmed COVID-19 were genotyped for the VDR ApaI, FokI, and TaqI variants using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. COVID-19 severity, the most commonly reported long-COVID-19 symptoms that lasted for >4 weeks from the onset of infection, and other variables were analyzed according to VDR genetic variants. In this study, ApaI and FokI polymorphisms showed no significant associations with COVID-19 severity (p > 0.05). However, a significant association was detected between the TaqI polymorphism and the severity of symptoms after infection with the SARS-CoV-2 virus (p = 0.04). The wild-type TaqI genotype was typically present in patients with mild illness, whereas the heterozygous TaqI genotype was present in asymptomatic patients. With regard to long-COVID-19 symptoms, the VDR heterozygous ApaI and wild-type TaqI genotypes were significantly associated with persistent fatigue and muscle pain after COVID-19 (p ˂ 0.05). Most carriers of the heterozygous ApaI genotype and carriers of the wild-type TaqI genotype reported experiencing fatigue and muscle pain that lasted for more than 1 month after the onset of COVID-19. Furthermore, the TaqI genotype was associated with persistent shortness of breath after COVID-19 (p = 0.003). Shortness of breath was more common among individuals with homozygous TaqI genotype than among individuals with the wild-type or heterozygous TaqI genotype. VDR TaqI is a possible genetic variant related to both COVID-19 severity and long-COVID-19 symptoms among Jordanian individuals. The associations between VDR TaqI polymorphisms and long-COVID-19 symptoms should be investigated in larger and more diverse ethnic populations.

Biochemical markers and FokI and TaqI vitamin D receptor genes polymorphism in rheumatoid arthritis

BackgroundPrevious studies have reported the role of genes in different metabolic processes in the human body, and any variation in gene polymorphisms could lead to disturbances in these processes and different diseases.ObjectiveThis study aimed to compare vitamin D receptor (VDR) FokI and TaqI genotypes in terms of parathyroid hormone (PTH) and some biomarkers of inflammation and susceptibility to rheumatoid arthritis (RA) disease.MethodsThis study included 100 patients with rheumatoid arthritis (RA). Genotyping was performed by polymerase chain reaction (PCR) and examined by specific restriction enzymes using restriction fragment length polymorphism (RFLP). Serum intact PTH, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), and anti-cyclic citrullinated peptide antibodies (ACCPs) levels were measured.ResultsAn increased PTH level (> 65 pg/ml) was found in 8% of patients. No significant differences among FokI and TaqI vitamin D receptor genes polymorphism regarding positive and negative RF or ACCPs were found. A significant difference was found among FokI (p = 0.009) and none in TaqI genotypes regarding intact parathyroid hormone level categories. No significant correlation was found between the serum intact PTH level and ESR or CRP levels (P = 0.13 and 0.28, respectively). The parathyroid hormone level was not a good predictor for RF or ACCPs (P = 0.5 and 0.06, respectively).ConclusionThe FokI gene may play a role in controlling PTH levels in patients with RA. There was no significant correlation found between the serum intact PTH level and RA severity according to ESR and CRP inflammatory biomarkers. There are no differences between VDR genes FokI and TaqI polymorphism in terms of RA susceptibility (for RF and ACCPs).

Some genetic differences in patients with rheumatoid arthritis

ObjectiveVitamin D is important for bone and cartilage metabolism. Changes in vitamin D blood level may be related to pathological disorders such as rheumatoid arthritis (RA). The main aim of this study is to investigate the association between RA and the vitamin D receptor (VDR) genes FokI and TaqI polymorphisms. One hundred RA patients and fifty healthy matched controls were assessed for VDR FokI and TaqI genotyping. Intact parathyroid hormone (PTH) and calcium (Ca) levels were measured, categorized, and compared between the cases and control groups.ResultsWe found that the FokI genotype frequencies for the RA cases and control groups were FF:Ff:ff = 46%:52%:2% and 50%:50%:0%, respectively (P = 0.76). The TaqI genotype frequencies for the RA cases and control groups were TT:Tt:tt = 45%:44%:11% and 42%:42%:16%, respectively (P = 0.69). A statistically significant high serum PTH level was associated with the ff genotype (p = 0.03), and a significantly low serum Ca level was associated with the TT genotype (p = 0.003). In comparison with controls, no influence of VDR FokI and TaqI genotypes on RA susceptibility or risk was demonstrated.

Increased susceptibility to complicated pneumonia among egyptian children with FokI (rs2228570), not TaqI (rs731236), vitamin D receptor gene polymorphism in association with vitamin D deficiency: a case-control study

BackgroundDetermining a genetic contribution to the development of complicated community-acquired pneumonia in children may help understand underlying pathogenesis. We aimed to investigate the association between two vitamin D receptor (VDR) gene polymorphisms, FokI and TaqI, and susceptibility to complicated pneumonia in Egyptian children compared to uncomplicated pneumonia. Associations with 25 hydroxy-vitamin D serum level were studied.MethodsThis was a case-control study that included 320 participants divided into 2 groups: patients and controls. The patients’ group included 100 children hospitalized with complicated pneumonia and 100 with uncomplicated pneumonia. 120 age and sex-matched apparently healthy children served as controls. The VDR FokI and TaqI polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. 25 hydroxy-vitamin D level was estimated in serum using ELISA.ResultsRegarding FokI, homozygous CC genotype was more common in complicated (52%) than uncomplicated pneumonia (28%) and controls (10%) (OR = 65; 95%CI (5.13-822.63), p < 0.001) and (OR = 4.3; 95%CI (0.7-27.16), p = 0.003), respectively. Children carrying C allele possessed 3 higher odds for complicated than uncomplicated pneumonia (OR = 3.08; 95%CI (1.33–7.14), p < 0.001). Heterozygous CT genotype increased susceptibility to complicated pneumonia (OR = 13.7; 95%CI (4.6–40.1), p < 0.001), not uncomplicated pneumonia (OR = 1.56; 95%CI (0.86–2.85), p = 0.145). Among complicated pneumonia, vitamin D level was lower in CC (6.92 ± 2.6ng/ml) than CT (9.55 ± 3.2 ng/ml) and TT genotype carriers (13.13 ± 3.6ng/ml) (p < 0.001). There was no significant difference between patients and controls as regards TaqI genotypes and alleles.ConclusionIn association with vitamin D deficiency, VDR gene FokI polymorphism, not TaqI, is a genetic risk factor for complicated pneumonia in Egyptian children.

Vitamin D and vitamin D receptor polymorphism in Asian adolescents with primary dysmenorrhea

BackgroundThe expression of vitamin D receptor in the normal endometrium and ovaries supports the role of vitamin D in local immunity and inflammatory cytokines regulation.ObjectiveThis study aimed to detect the relation between serum 25(OH)D and primary dysmenorrhea in Asian Adolescents.MethodsTwo hundred and five (205) adolescents complaining of primary dysmenorrhea (study group) were compared in this prospective study to matched controls (210 controls) after informed consent following the Helsinki Declaration.After thorough evaluation, including a thorough history and pelvic ultrasound examination, blood samples were collected from the studied adolescents to measure serum 25(OH)D and for vitamin D receptor TaqI (rs731236) genotyping.The studied adolescents’ data were analyzed using the Pearson’s correlation to detect the relation between serum 25(OH)D and primary dysmenorrhea (primary outcome). The secondary outcome measures the odds of primary dysmenorrhea in Asian adolescents with vitamin D receptor TaqI (rs731236) polymorphism.ResultsThe serum 25(OH)D was significantly lower in the studied-dysmenorrhea group compared to controls (16.17 ± 7.36 versus 17.65 ± 6.36 ng/ml, respectively), (P = 0.01). The correlation analysis showed a significant negative correlation between the serum 25(OH)D and visual analogue scale of dysmenorrhea (r = -0.9003, P < 0.0001).The studied-dysmenorrhea cases with vitamin D receptor T/t and t/t genotypes had significantly lower serum 25(OH)D (16.7 ± 8.05 and 14.4 ± 4.1 ng/ml, respectively) compared to controls (18.97 ± 6.7 and 21.4 ± 2.45 ng/ml, respectively), (P = 0.02 and 0.004, respectively).The VDR T/t and t/t polymorphisms significantly increase the odds of primary dysmenorrhea (OR 1367.2, P < 0.0001 and OR 106.2, P = 0.001, respectively).ConclusionThe serum 25(OH)D was significantly lower in the studied-dysmenorrhea group compared to controls. The studied-dysmenorrhea cases with VDR T/t and t/t TaqI genotypes had significantly lower serum 25(OH)D compared to controls. The VDR T/t and t/t polymorphisms significantly increase the odds of primary dysmenorrhea.

Differences in Chronic Low-Grade Inflammation and Metabolic Disturbances between VDR Genotypes in an Ethnically Homogenous Postmenopausal Female Population from Poland.

(1) Vitamin D deficiency and changes in the endocrine system may stimulate systemic inflammation. VDR expression and the vitamin D concentration decrease with age, which is important in postmenopausal women for whom estrogen deficiency causes rapid bone loss. This group is, moreover, particularly at risk of developing atherosclerosis and its adverse consequences, such as chronic inflammation. The aim of this study was to assess the differentiation by the VDR genotype of the risk factors for so-called chronic low-grade inflammation and metabolic disorders. (2) We studied the differences between the anthropometric, metabolic, and inflammation parameters of VDR genotypes for Apa-I, Bsm-I, Fok-I, and Taq-I in a sample of 321 women aged 50-60 from an ethnically homogeneous urban population in Poland. (3) The TT Taq-I genotype presented a significantly higher rate of insulin resistance (HOMA) and lower serum levels of adiponectin than the other two genotypes. The AA genotype of the Bsm-I polymorphism was associated with a more atherogenic serum profile and significantly higher LDL and LDL/HDL values and Castelli Index. (4) Chronic low-grade inflammation was associated with the TT Taq-I genotype and presented a higher rate of insulin resistance. The AA genotype of the Bsm-I polymorphism presented a more atherogenic serum lipid profile and, therefore, a higher risk of developing cardiovascular disease.

A Pilot Study of the Association VDR Polymorphisms With Primary Hyperparathyroidism.

Primary hyperparathyroidism (PHPT) is the third most common endocrine disorder characterized by autonomous parathyroid hormone (PTH) production from one or more parathyroid glands and hypocalcemia. Vitamin D through its receptor is a principal regulator of parathyroid glands function. VDR gene polymorphisms, which affect the expression or structure of VDR protein, may be involved in the genetic pathogenesis of PHPT. The aim of this study was to investigate the role of FokI, ApaI, TaqI, and BsmI VDR gene polymorphisms as genetic predisposing factors for PHPT. Fifty unrelated patients with sporadic PHPT and an equal number of corresponding ethnicity, sex and age range healthy volunteers were enrolled in the study. Genotyping was performed with polymerase chain reaction and restriction fragment length polymorphism assay. Statistically significant difference was observed in TaqI genotype distribution between PHPT patients and controls, while no association was detected for the other studied polymorphisms. TaqI TT and TC genotypes may be associated with PHPT risk in Greek population. Further independent studies are needed to replicate and validate the role of VDR TaqI polymorphism in PHPT predisposition.

TaqI polymorphism T/t genotypes at the vitamin D receptor gene (VDR) are associated with increased serum vitamin D levels in mild and moderate psoriasis vulgaris: A pilot study.

Several types of polymorphisms in vitamin D receptor (VDR) have been found in psoriasis. This study looked at the role of the TaqI polymorphism in the VDR gene as a factor in changing plasma 25-hydroxyvitamin D [25(OH)D] levels in psoriasis patients and to see if it had any relationship with disease severity. Clinical examination, serum 25(OH)D level measurement, molecular studies and TaqI genotyping by PCR and RFLP were performed for the two groups. The T/t genotypes of TaqI polymorphism genotypes were most common in patients, while the t/t genotypes were more abundant in healthy subjects. The T allele was high in the patient group in comparison with the normal subjects, but there were no significant differences (p= 0.421). Patients with T/t TaqI genotypes had higher levels of 25(OH)D than those with T/T and t/t (p= 0.004). Moderate psoriatic patients with the T/t genotype had relatively high 25(OH)D levels compared with moderate patients with the T/t and t/t genotypes (p= 0.001). The increase in 25(OH)D titers in moderate patients is greater than that in mild and severe patients. T/t genotypes are associated with increased 25(OH)D levels in moderate and mild patients.

Association of VDR gene ApaI polymorphism with obesity in Iranian population

:Introduction: Identifying obesity risk factors as a health problem facing communities is crucial given its complexity. The vitamin D receptor gene has been reported as a possible cause of this disease.Objective: To study the association of the VDR gene ApaI, BsmI, and TaqI polymorphisms with obesity in an Iranian population.Material and methods: We analyzed the genotypes of 348 obese (BMI≥30 kg/m2) and 320 non-obese people (BMI: 18.5-24.9 kg/m2) using PCR-RFLP. We measured FBS, TG, total cholesterol, and HDL and LDL cholesterol levels in an automatic biochemical analyzer.Results: We found significantly higher BMI, FBS, and TG levels in the obese group compared to the control. In the obese individuals, the frequency of genotype AA was 47.1% and that of the combined Aa+aa genotype, 52.9% while in the control group they were 30% and 70%, respectively (p=0.024, 95% confidence interval (CI)=1.100-3.933, odds ratio (OR)=2.08). A and a alleles frequencies for the ApaI polymorphism were statistically significant in the two groups (allele A vs. a; p=0.017). No significant relationship was observed between TaqI genotypes and alleles in the control and obese subjects.Conclusion: We found that VDR ApaI (rs7975232 C/A) polymorphism appeared to be a risk factor for obesity. Especially, the A allele and the AA genotype in ApaI were associated with the obesity phenotypes.

Assessment the effect of vitamin D supplementation on plasma vitamin D levels, inflammation, and oxidative stress biomarkers based on vitamin D receptor genetic variation in breast cancer survivors: a protocol for clinical trial

BackgroundBoth human genes and environmental exposures, due to complex interplay, play important role in the cancer etiology. Vitamin D is associated with a reduced risk of incidence and mortality of several human cancers. This study will aim to investigate the possible effects of individual polymorphisms in vitamin D receptor (VDR) as well as effects of VDR haplotypes on response to vitamin D supplementation in breast cancer survivors.MethodsThis is an interventional study in which the effects of vitamin D supplementation on plasma vitamin D levels, inflammatory and antioxidant biomarkers and factors associated with cell proliferation, differentiation, damage, and apoptosis will be investigated stratified by variations in VDR genotype. The present study will be conducted on breast cancer survivors referred to the Shohadaye Tajrish hospital and its associated clinics. One hundred ninety-eight breast cancer survivors will receive 4000 IU of vitamin D3 daily for 12 weeks. VDR Fok1, ApaI, TaqI, BsmI, and Cdx-2 genotype will be determined at the end of the study and responses to vitamin D supplements (inflammatory, antioxidant, cell proliferation, differentiation, damage, and apoptosis biomarkers) will be compared between the three subgroups of each VDR polymorphism as well as different VDR haplotype categories.DiscussionGenetic variation is a fundamental factor influencing individuals’ divergent responses to diet, nutritional status, metabolic response, and diet-related health disorders. Furthermore, studies of gene and environment interactions will provide a precise and accurate assessments of individuals’ dietary requirements by considering both the genetic and environmental aspects simultaneously. The results of the current study, to some extent, will highlight the discrepancies existing in the findings of different studies regarding vitamin D, VDR, and cancer by considering both the genetic and environmental aspects simultaneously. If responses to vitamin D supplementation could be modified by VDR SNPs, determining the distribution of VDR polymorphisms in both breast cancer survivors and healthy populations will provide a new insight into the vitamin D requirements of individuals to prevent cancer and its related mortality based on their genotypes.Trial registration This trial has been registered on Iranian Registry of Clinical Trials (IRCT) under the identification code: IRCT2017091736244N1, registration date: 2017-11-10, http://www.irct.ir/trial/27153

Narrative role of vitamin D receptor with osteoporosis and obesity in a sample of Egyptian females: a pilot study

BackgroundVitamin D receptor (VDR) is known as one of the cellular regulators for several metabolic pathways indicating its pivotal role in the pathological pathway of numerous diseases. Considering the high frequency of osteoporosis and obesity among women, the current study aimed to explore the prospective assembly of the most frequent two VDR loci, single nucleotide polymorphism SNPs rs731236 (TaqI) and rs7975232 (ApaI) with a genetic predisposition to osteoporosis (skeletal) and obesity (chronic non-skeletal disorders), in Egyptian women. This was a cross-sectional study, including 97 Egyptian females (25–65 years), randomly chosen, from all employees and workers of the National Research Centre, Egypt. Anthropometric measurements (weight, height, BMI), dual-energy X-ray absorptiometry (DEXA), and molecular genetic analysis were done. ResultsThe variation of ApaI genotype between the normal and osteoporotic groups denotes a remarkable association of the homozygote ApaI genotype with osteoporosis risk. Among the normal weight group, bone mineral density (BMD) was significantly associated with TaqI VDR gene polymorphism as the presence of the heterozygote genotype was accompanied with higher BMD while the homozygote one was detected with lower BMD. Also, TaqI VDR gene polymorphism was significantly associated with BMI when participants were divided according to the presence of osteoporosis; increased BMI was expressed in the non-osteoporotic women group carrying the homozygote genotype of Taq I VDR gene while the presence of the heterozygote genotype (TaqI) in the osteoporotic group was associated with increased BMI. ConclusionsThe heterozygote TaqI genotype is protective against the osteoporosis phenotype and accompanied with increased BMI among osteoporotic women, while the homozygote ApaI genotype has a significant association with osteoporosis risk.

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.

Influence Of Genetic Variability Related To Bone Remodeling and Cytokine Profile In The Development Of Bone Involvement In Gaucher Disease

IntroductionBone disease (BD) is one of the most debilitating and disabling complication of Gaucher disease (GD), leading to bone marrow infiltration by Gaucher cells, failure of remodelling, skeletal changes including osteolysis, osteopenia and intraosseous vascular complications. The most important factor involved in bone remodeling is the genetic component, which may explain between 60% and 80% of bone mass variability. In addition, Gaucher cells activate and induce proinflammatory cytokines synthesis that can modify the activity of osteoblast-osteoclast system and promote lytic phenomena. AimTo analyze the genetic variability in genes related to bone remodeling and to identify the cytokine profile in GD1 patients associated with BD in order to characterize bone markers in GD that can predict the degree of BD. MethodsA total of 18 polymorphisms located in 8 genes (COL1A: -1997,-1663, 1245; ESR1: PvuII, XbaI;(TA)n; VDR: FokI BsmI, ApaI, TaqI, -1012, -1521; BMP4: 6007; ClCN7: V418M; IL6R: -208, D358A; OPG: 950, -1181; OPN: -156) were analyzed by RFLP and DNA sequencing. Furthermore a panel of cytokines: IL4, IL6, IL7, IL10, IL13, MIP1α, MIP1β and TNFα were analyzed in plasma samples by Luminex®100 platform and Millipore cytokine kits. BD was evaluated by X-ray in a group of 83 GD1 patients. Of them 30 presented BD (females 42.5%, mean age: 40 year; range: 20-67). Data were analyzed using Kolmogorov-Smirnov analysis, t-test or Mann-Whitney-U-test, one-Way ANOVA or Kruskall-Wallis test and correlations using the Spearman correlation. ResultsSignificant differences were observed among VDR TaqI genotypes of normal and bone affected patients (p<0.05) and in MIP-1α concentration between affected and non-affected patients. Significant positive correlations were found in non-BD group between IL10/ IL13/IL4/IL6/IL7; MIP1α/MIP1β/IL6/IL7 and in bone affected group between IL10/IL4/IL7/TNFα and IL6/IL13. ConclusionsThese data suggest that the VDR TaqI genotype and MIP-1α concentration have a predictive value in GD bone involvement. Moreover the different correlations between cytokines in the different groups could indicate different bone signal activation pathways.This work was partially financed by a grant from Genzyme a Sanofi Company and Fundación Española para el Estudio y Terapeutica de la Enfermedad de Gaucher (FEETEG) y otras lisosomales. Disclosures:No relevant conflicts of interest to declare.

Clinical and epidemiological differences in the course of psoriasis in children depending on Vitamin D levels and genotypes of the TaqI polymorphic variant of the VDR gene

When grouping children with psoriasis depending on TaqI (T/C) genotypes of the VDR gene, the youngest age of disease onset and the longest duration of dermatitis (5.60 ± 0.77 years and 4.90 ± 0.68 years, respectively) showed up in case of the CC genotype. In case of the TT genotype, disease onset coincided with an older age, and the history of present illness was the shortest (10.26 ± 0.64 years and 2.59 ± 0.58 years, respectively). PASI (20.32 ± 3.43) and BSA (40.00 ± 6.11) severity indices were the highest and of statistically significant difference to those in other groups in the presence of the CC genotype. In case of the TC genotype, the index PGA (2.80 ± 0.15) was the lowest and made a statistically significant difference to the values of other groups. A negative correlation between vitamin D levels and the PASI, PGA, BSA was identified in children holding CC and TC genotypes. Conclusion: The clinical presentation of dermatitis and its epidemiological features in children with psoriasis, namely the age of disease onset, duration of exacerbation, body surface area and the intensity of psoriasis symptoms depend on vitamin D serum levels and genotypes of the TaqI polymorphic variant of the VDR gene.

Relationship between vitamin D receptor gene polymorphisms (BsmI, TaqI, ApaI, and FokI) and calcium intake on bone mass in young Japanese women

BackgroundThe high prevalence of low bone mass in young women in Japan has emerged as a serious health issue in recent years. Therefore, the aim of the present study was to reevaluate the relationship between genetic and dietary factors, as well as its influence on bone mass in young Japanese women, with particular emphasis on vitamin D receptor (VDR) gene polymorphisms and calcium intake.MethodsA total of 499 Japanese women aged 20–24 years were enrolled in the study. The bone mass of the calcaneus was assessed using the quantitative ultrasound method and expressed as the osteo sono-assessment index (OSI). VDR gene polymorphisms (BsmI, TaqI, ApaI, and FokI) were analyzed using DNA extracted from saliva. Calcium intake was assessed using the Food Frequency Questionnaire based on food groups (FFQg) and adjusted with the energy intake. Participants were divided into two groups based on the median calcium intake (250 mg/1000 kcal).ResultsConsequently, bone mass was significantly different among the BsmI and TaqI genotypes after adjusting for body mass index (BMI) (p = 0.030 and 0.019, respectively). In addition, the BsmI AA and ApaI GT genotypes showed significant differences in bone mass between the calcium-intake groups, with low OSI in the low-calcium intake group and high OSI in the high-calcium intake group, respectively, even after adjusting for BMI (p = 0.020 and 0.038, respectively).ConclusionsThese findings may prove instrumental in developing a logical approach towards preventing bone loss in young Japanese women.

Vitamin D receptor gene polymorphisms and risk of hepatocellular carcinoma in hepatitis C-related liver cirrhosis

BackgroundHCV is a major risk factor for HCC; however, the exact mechanism of hepatocarcinogenesis is still not fully understood. Host genetic factors have been reported to play a significant role. Experimental studies support the tumor inhibitory effect of vitamin D on HCC cells. Several single nucleotide polymorphisms (SNPs) have been depicted in the vitamin D receptor (VDR) gene. We aimed to assess whether any of these polymorphisms could be significantly associated with increased risk of HCC.ResultsThis study was conducted on 76 patients with HCV-related liver cirrhosis (48 patients had HCC on top of cirrhosis, and the other 28 had liver cirrhosis only). All patients underwent full medical history assessment, clinical examination, laboratory investigations, abdominal ultrasonography, and genotyping of the VDR gene. HCC patients had a significantly higher frequency of ApaI CC genotype compared with those patients without HCC. There is no statistically significant difference between the studied groups at any TaqI genotypes, but the carriage of the ApaI CC genotype had a significant association with liver disease severity in both patients groups compared with ApaI CA/AA genotypes. The carriage of the ApaI CC genotype was an independent predictor for HCC in HCV-related liver cirrhosis.ConclusionsVDR ApaI polymorphism is significantly associated with the development of HCC; thus, ApaI CC genotype could be used as an important molecular marker to predict the risk of HCC in patients with HCV-related liver cirrhosis.

Vitamin-D Receptor-Gene Polymorphisms Affect Quality of Life in Patients with Autoimmune Liver Diseases.

Vitamin D deficiency has been associated with depressive symptoms and reduced physical functioning. The aim of the study was to characterize the relationship between polymorphisms of the vitamin D receptor (VDR) gene and the quality of life in patients with autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC). Three polymorphisms of the VDR gene (TaqI-rs731236, BsmI-rs1544410, and ApaI-rs7975232) were analyzed in patients with AIH (n = 142) and PBC (n = 230) and in healthy individuals (n = 376). Patient quality of life was assessed by validated questionnaires such as Medical Outcomes Study Short-Form 36 (SF-36), State Trait Anxiety Inventory (STAI), Modified Fatigue-Impact Scale (MFIS), Patient-Health Questionnaire 9 (PHQ-9), and PBC-40. The TaqI C and ApaI A alleles are risk alleles in both AIH and PBC, and a significant dominance of the A allele in BsmI was observed in AIH patients. In terms of quality of life, the presence of the CC or CT TaqI genotype was associated with emotional reactions, including the fatigue and the cognitive skills of patients with PBC, whereas in the group of AIH patients, homozygotes CC of TaqI, AA of BsmI, and AA of ApaI had worse physical, social, emotional, and mental function. The genetic variations of VDR gene can influence individual susceptibility to develop chronic autoimmune liver diseases such as AIH and PBC and affect quality of life.

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

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

Association of vitamin D receptor gene FokI and TaqI polymorphisms and risk of RDS

Background: Vitamin D and its receptor (VDR) have important roles in perinatal lung development. The objective of this study was to investigate the possible association between VDR FokI and TaqI polymorphism and development of respiratory distress syndrome (RDS) in preterm infants.Method: A total of 173 premature infants <34 weeks: 82 with RDS and 91 without RDS were enrolled. Genotyping of VDR polymorphisms was assayed by real-time PCR. Serum 25-hydroxyvitamin D (25-OHD) levels were measured by ELISA in blood samples that were obtained at the time of admission to the neonatal intensive care unit.Results: Gestational age (GA) was significantly lower in the RDS group compared with the controls. In univariate analysis, VDR TaqI CT and CC genotypes were associated with the increased risk of RDS (OR = 3.264, p = .001, 95% CI = 1.597–6.672 and OR = 5.222, p < .001, 95% CI = 2.165–12.597, respectively); while VDR FokI showed no association with RDS. In multivariate logistic regression analysis, variant TaqI genotype increased risk of RDS (p = 0.001, OR = 3.464, 95% CI = 1.655–7.251) independent of gestational age, birth weight and gender. 25-OHD levels in the RDS group were significantly lower compared with those in without the RDS group (p = .002). Serum 25-OHD levels were not significantly different among the different FokI and TaqI genotypes in RDS group.Conclusions: This is the first report of association of VDR polymorphism with RDS development in preterm neonates. Current study suggests that VDR TaqI polymorphism may be involved in predisposition to RDS in premature neonates. Further studies are needed to assess the contribution of vitamin D and VDR signaling to the pathogenesis RDS

Association of Vitamin D receptor (TaqI, BsmI, and FokI) polymorphisms with prediabetes and Type 2 diabetes in Asian Indians

Background: Vitamin D deficiency is known to be involved in the development of insulin resistance and type 2 diabetes (T2D), and the functions of Vitamin D are mediated through Vitamin D receptor (VDR). Only a few reports are available in the Asian Indian population highlighting the role of VDR polymorphism in diabetes. We aimed to investigate the association of VDR gene polymorphisms (TaqI, BsmI and FokI) with prediabetes (PD) and T2D and their relationship with anthropometric and biochemical parameters in Asian Indians. Subjects and Methods: In this study, 454 participants including 147 with normal glucose tolerance (NGT), 145 with PD, and 162 with T2D were enrolled in this study. Genetic variants of the VDR were genotyped using polymerase chain reaction-restriction fragment length polymorphism method. Anthropometric measurements were done in all participants. Results: The most common genotypes for TaqI, BsmI, and FokI were TC, GA, and CC, respectively. The allele distribution of TaqI differed significantly when compared between NGT and T2D group. A significant protection was shown against T2 in VDR TaqI genotypes after adjusting for age, gender, and Body Mass Index. The levels of homeostatic model assessment for insulin resistance, fasting insulin, and the waist-hip ratio were significantly higher in TT genotype when compared with TC + CC genotype of TaqI polymorphism in NGT. In PD group, the levels of serum cholesterol and low-density lipoprotein cholesterol were significantly higher in AA genotype when compared with GA + GG genotype in BsmI polymorphism. Conclusions: The study indicates VDR TaqI, and BsmI polymorphisms seem to influence anthropometric and biochemical parameters, and in particular, VDR TaqI polymorphism offers protection against T2D in Asian Indians.