RESUMEN
Vitamin D status has been involved with coronavirus disease 19 (COVID-19) severity. This may be mediated by vitamin D metabolism regulatory genes. Of interest is the vitamin D receptor (VDR) gene, which has been previously associated with other inflammatory and respiratory diseases. In order to investigate the role of VDR gene polymorphisms in COVID-19 severity and outcome, a total of 292 COVID-19 patients were classified according to severity in moderate (n = 56), severe (n = 89) and critical (n = 147) and, according to outcome in survivor (n = 163) and deceased (n = 129), and analysed for FokI and TaqI VDR gene polymorphisms by polymerase chain reaction-based restriction enzyme digestion. The FokI and TaqI single nucleotide polymorphisms (SNPs) were not associated with COVID-19 severity or mortality individually but when analysed by haplotype, TC was associated with an increased risk of presenting critical COVID-19. Additionally, FokI CT genotype was more frequent in COVID-19 patients with hypertension, and T allele carriers presented higher aspartate aminotransferase levels. Our results suggest a relationship between VDR FokI and TaqI SNPs and COVID-19 severity in Mexican population. Although there are some previous reports of VDR polymorphisms in COVID-19, this represents the first report in Latin American population. Further studies on other populations are encouraged.
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COVID-19 , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Receptores de Calcitriol , SARS-CoV-2 , Índice de Severidad de la Enfermedad , Humanos , Receptores de Calcitriol/genética , COVID-19/genética , Femenino , México , Masculino , Persona de Mediana Edad , Anciano , Haplotipos , Adulto , Alelos , Genotipo , Estudios de Cohortes , Frecuencia de los GenesRESUMEN
(1) Background: Obesity and its comorbidities can cause burdens and limitations. Bariatric surgery (BS) is indicated as a safe procedure to reduce body mass and improve present comorbidities. However, several complications were reported, such as vitamin D [25(OH)D] deficiency. We evaluated if 25(OH)D serum levels relate to clinical characteristics, symptoms, or habits in women after their BS, and whether the vitamin D receptor (VDR) gene's TaqI and FokI polymorphisms affected 25(OH)D levels and the total body bone mineral density (TBBMD). (2) Methods: This cohort cross-sectional comparative analytical prospective study consisted of 27 women, 61.6 ± 5.0 years, submitted to BS one year prior at a public reference hospital, DF-Brazil. All participants were asked to follow the physical and dietary activity recommendations and received vitamin D3 supplements. Their anthropometric, biochemical, and immunological measurements and blood samples were obtained. (3) Results: 73.3% of participants had low 25(OH)D levels, and their levels correlated positively with TBBMD and negatively with systolic pressure. VDR TaqI did not affect 25(OH)D levels, whereas VDR FokI's allele f presence correlated to a median rise in 25(OH)D levels. Neither polymorphism correlated to TBBMD. (4) Conclusions: 25(OH)D levels were positively correlated with TBBMD, negatively with systolic blood pressure, and were higher in those with the VDR FokI allele f.
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Cirugía Bariátrica , Receptores de Calcitriol , Vitamina D , Anciano , Femenino , Humanos , Estudios de Casos y Controles , Estudios Transversales , Predisposición Genética a la Enfermedad , Genotipo , Polimorfismo Genético , Estudios Prospectivos , Receptores de Calcitriol/genética , Vitamina D/sangre , Vitaminas , Persona de Mediana EdadRESUMEN
Vitamin D (VD) deficiency is more frequent in systemic lupus erythematosus (SLE) patients than in control subjects (CS); genetic variants in the VD receptor (VDR) could contribute to the clinical disease activity. This study was aimed to determine the association of the VDR variants FokI (rs2228570), BsmI (rs1544410), ApaI (rs7975232), and TaqI (rs731236) with susceptibility to the disease, VD status, VDR mRNA expression, and clinical disease activity in SLE patients. A cross-sectional study was conducted in 194 SLE and 196 CS Mexican women. Immunoassays quantified serum calcidiol and calcitriol. Genotyping was performed by allelic discrimination assays and mRNA VDR expression by qPCR. The FokI variant was not in linkage disequilibrium with BsmI, ApaI, and TaqI VDR variants. SLE patient carriers of the TT FokI genotype showed higher clinical disease activity scores. Notably, the mRNA VDR expression was higher in SLE patients vs. CS, in active vs. inactive SLE patients, and in participants of both study groups with vitamin D deficiency, higher calcitriol levels, and TT FokI genotype carriers. In conclusion, the TT FokI VDR genotype was related to high VDR expression and clinical disease activity in systemic lupus erythematosus patients.
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Lupus Eritematoso Sistémico , Receptores de Calcitriol , Humanos , Femenino , Receptores de Calcitriol/genética , Predisposición Genética a la Enfermedad , Calcitriol , Estudios Transversales , Estudios de Casos y Controles , Genotipo , Lupus Eritematoso Sistémico/genética , ARN Mensajero/genéticaRESUMEN
BACKGROUND: FokI (rs2228570 T>C) and BsmI (rs1544410 A>G) polymorphisms of the vitamin D receptor (VDR) have been associated to abnormal glucose metabolism and could be inversely associated with ß-cell function (BCF) and vitamin D status. There is a lack of information about this topic in the Mexican population. AIM OF THE STUDY: To evaluate the relationship between VDR gene polymorphisms FokI and BsmI with BCF and vitamin D status in a population of non-obese Mexican adults. METHODS: A sample of 192 participants were enrolled during 2016-2018. Blood samples were collected to determine fasting concentrations of glucose, insulin, and vitamin D. Genomic DNA was isolated from leucocytes and the polymorphic variants of FokI and BsmI were analyzed. The Homeostasis Model Assessment Calculator was used to estimate the BCF (HOMA2-B). RESULTS: FokI polymorphism showed a frequency of 20.1% for homozygous TT carriers and 7.8% for the BsmI GG. The recessive model of FokI (TT genotype) showed a lower mean value of BCF compared to the combination of CC + CT (99.2 vs. 109.6%, p = 0.045). Likewise, significantly lower mean values of HOMA2-B and insulin were observed for BsmI (GG genotype, p = 0.016 and p = 0.039, respectively). After covariates adjustment, only FokI polymorphism remained as an independent predictor of BCF. CONCLUSIONS: the TT and GG variants of the FokI and BsmI polymorphisms are related to a decrease in FCB. In the case of FokI, this decrement was independent of insulin sensitivity, vitamin D levels, percentage of body fat, gender, and age.
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Insulinas , Receptores de Calcitriol/genética , Adulto , Estudios de Casos y Controles , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Polimorfismo Genético , Polimorfismo de Nucleótido Simple , Vitamina DRESUMEN
The objective of this review was to investigate the effect of vitamin D3 supplementation on serum 25-hydroxyvitamin D concentration in individuals with single-nucleotide polymorphisms in the vitamin D receptor gene. The research was conducted on 241 articles found in the PubMed, Scopus, Science Direct, and Cochrane Library databases between November and December 2018. After article screening, three randomized double-blind placebo-controlled clinical trials were identified as eligible for this review. Participants were Australian, Brazilian, and Chinese individuals, who ingested doses of vitamin D3 ranging from 2000 IU to a megadose of 200,000 IU. The presence of the BB/Bb genotype of the BsmI polymorphism and the FokI G allele caused an increase in the serum concentrations of vitamin D after supplementation. Nonetheless, the few studies on this subject are not unanimous in their results. It is possible that differences among populations, sample sizes, doses, and time of supplementation have an impact on data and outcomes.
El objetivo de esta revisión fue investigar el efecto de la suplementación con vitamina D3 sobre la concentración sérica de 25-hidroxivitamina D en individuos con los polimorfismos de un solo nucleótido en el gen del receptor de la vitamina D. La investigación se realizó en 241 artículos encontrados en las bases de datos PubMed, Scopus, Science Direct y Cochrane Library entre noviembre y diciembre de 2018. Después de la selección del artículo, se identificaron tres ensayos clínicos aleatorios, controlados con placebo, doble ciego, como elegibles para esta revisión. Los participantes fueron australianos, brasileños y chinos, quienes ingirieron dosis de vitamina D3 que iban desde las 2000 UI hasta una megadosis de 200,000 UI. La presencia del genotipo BB / Bb del polimorfismo BsmI y el alelo FokI G causó un aumento en las concentraciones séricas de vitamina D después de la suplementación. No obstante, los pocos estudios sobre este tema no son unánimes en sus resultados. Es posible que las diferencias entre poblaciones, tamaños de muestra, dosis y tiempo de suplementación tengan un impacto en los datos y resultados de la investigación.
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Humanos , Vitamina D/sangre , Receptores de Calcitriol/genética , Colecalciferol/administración & dosificación , Polimorfismo Genético , Colecalciferol/farmacologíaRESUMEN
BACKGROUND AND AIMS: The impact of host genetic variation in susceptibility of tuberculosis is well documented. The vitamin D receptor gene (VDR) is a transacting transcription factor which mediates innate immune response by enhancing the expression of several antimicrobial peptides, including cathelicidin. An association between VDR polymorphisms with tuberculosis (TB) has been investigated in different ethnic groups; however there are contradictions and inconsistencies in the results. The aim of this study was to evaluate the association between polymorphisms of functional VDR with the susceptibility to pulmonary tuberculosis in a Mexican population. METHODS: A case-control study was performed in, 257 patients with pulmonary tuberculosis and 457 healthy controls recruited from: family medicine clinics of the Mexican Social Security Institute. The VDR gene polymorphisms Fok I (rs 2228570), BsmI (rs1544410), ApaI (rs7975232) and TaqI (rs731236) were genotyped by TaqMan assays. Statistical analysis was performed using: Epi Info V-7 and SNP Stats software. RESULTS: No statistically significant associations were observed in genotype and haplotype distribution between BsmI, ApaI and TaqI polymorphisms and disease susceptibility. The CC genotype for the VDR gene FokI was significantly more frequent in patients than in controls (29.6% versus 17.5%, OR=1.97; 95% CI=1.37-2.8, PC=0.0004). Moreover, TT genotype was decreased in patients as compared to the control group (24.1% versus 34.8%, OR=0.59; 95% CI=0.42-0.84, PC=0.004). CONCLUSION: To our best knowledge, this is the first case-control study that finds an association between CC genotype of FokI SNP in the VDR gene with pulmonary tuberculosis in Mexican patients. However more validation studies should be performed to prove our conclusions.
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Receptores de Calcitriol/genética , Tuberculosis Pulmonar/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , México , Persona de Mediana Edad , Polimorfismo Genético , Polimorfismo de Nucleótido Simple , Adulto JovenRESUMEN
AIM: The aim of the present study was to evaluate the distribution of single-nucleotide polymorphisms (SNP) (variants FOKI [rs2228570], CDX2 [rs47908762], and GATA [rs4516035]) in the vitamin D receptor in individuals with type 2 diabetes mellitus and chronic periodontitis (DM2 + CP), CP alone, and healthy individuals, and to investigate the relationship with susceptibility to CP. METHODS: In total, 280 individuals (116 with DM2 + CP, 95 with CP alone, and 69 healthy individuals) were genotyped using real-time polymerase chain reaction with allele-specific probes. Significant differences (P < .05) were found among the groups with regard to socio-epidemiological variables (sex, marital status, income, smoking habit, and schooling) and clinical-epidemiological variables (age, number of teeth, probing depth, clinical attachment loss, gingival bleeding index, and visible plaque index). RESULTS: The C allele was significantly more frequent among the healthy individuals (34.8%) than those with DM2 + CP (23.5%) (odds ratio [OR] = .58, 95% confidence interval [CI]: . 35-.94, P = .022). Likewise, the CC allele was significantly more frequent among healthy individuals (11.6%) than those with DM2 + CP (2.6%) (OR = .17, 95% CI: .03-.79, P = .015). CONCLUSION: The results suggest that the presence of these variants could lead to a lower susceptibility to DM2 and CP. No other significant differences among groups were found for the other SNP investigated.
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Factor de Transcripción CDX2/genética , Periodontitis Crónica/genética , Diabetes Mellitus Tipo 2/genética , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Receptores de Calcitriol/genética , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Brasil , Estudios de Casos y Controles , Periodontitis Crónica/complicaciones , Periodontitis Crónica/epidemiología , Índice de Placa Dental , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Femenino , Genotipo , Técnicas de Genotipaje , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Adulto JovenRESUMEN
Preterm birth (PTB) is featured by less than 37weeks of gestational age or fewer than 259days since the first day from the last menstrual period. Complications of PTB are the major cause of neonatal deaths, several factors are linked to PTB increased risk including immunological and genetics. Vitamin D plays an important role in immune response modulation and its action occurs through the vitamin D receptor (VDR), which recently has been described as overexpressed in human placenta during the pregnancy. Herein we assessed two single nucleotide polymorphisms (SNPs) FokI (rs2228570 A>G) and Cdx-2 (rs11568820 T>C), within VDR, using TaqMan fluorogenic probes, and differential susceptibility to SPTB. We assessed 104 pregnant women with SPTB and 85 women with normal birth in a Northeastern Brazilian population. Statistically significant differences for both SNPs where found when comparing allele and genotype frequencies in both groups: the T allele for rs2228570 and A allele for rs11568820 were significantly more frequent in SPTB group than in normal birth group (p=0.000013 and p=0.00466, respectively). The rs11568820 A/A genotype was associated to clinical/demographic variables such as: premature birth (p=0.007), neonate weight (p=0.039), presence of infection during pregnancy (p=0.011) and premature birth among multiparous (p=0.015). The rs2228570 T/T genotype associated with gestational diabetes mellitus (p=0.044) and chorioamnionitis during pregnancy (p=0.043). In conclusion our findings indicate an association between polymorphisms FokI and Cdx-2 within VDR gene and SPTB, suggesting their involvement in the triggering of these syndromes.
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Polimorfismo de Nucleótido Simple , Nacimiento Prematuro/genética , Receptores de Calcitriol/genética , Brasil , Estudios de Casos y Controles , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Embarazo , Factores de RiesgoRESUMEN
INTRODUCTION: FokI polymorphism has been associated with obesity and type 2 diabetes (T2D) in some populations. OBJECTIVE: To investigate the frequencies of a genetic polymorphism of Vitamin D receptor (FokI) in patients with T2D and control subjects and investigate the role of 1,25(OH)2D3 in the expression of pro-inflammatory markers in peripheral blood mononuclear cells (PBMCs). METHODS: The case-control study was conducted in 160 patients with T2D and 160 control subjects, men and women (30-74 years old). The genotype and allele frequency of FokI polymorphisms were determined in these subjects. Subsequently a subgroup of 40 subjects was included from which PBMCs were removed. In vitro, the culture medium was supplemented with two different concentrations of 1,25(OH)2D3(10- 8 M and 10- 10 M). The expression profiles of TNFα and mRNA were analysed by qPCR, and GAPDH and ß-actin were used as housekeeping genes. RESULTS: The control subjects have an increased frequency of the FF genotype. In subjects with T2D, the ff genotype was associated with higher HOMA-IR values than individuals with genotype Ff (p = 0.021). In vitro study in PBMCs showed differential expression of TNFα mRNA by FokI genotype, with a lower expression of this marker of inflammation in FF genotype subjects at a concentration of 10- 8 M of 1,25(OH)2D3. CONCLUSION: Our data suggest that VDR FokI polymorphism is associated with T2D, and the genotypes Ff and ff of this variant show a reduced response or resistance to the anti-inflammatory action of VitD, which could indicate a functional role of FokI polymorphism of VDR.
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BACKGROUND: Vitamin D deficiency and single nucleotide polymorphisms (SNP) in the gene encoding vitamin D receptor (VDR) have been associated with asthma. OBJECTIVE: To compare 25-hydroxyvitamin D (25OHD) levels and the frequency of 3 SNPs in the VDR gene between asthmatic and healthy children. METHODS: In persistent asthmatic and healthy control children, the 25OHD levels were measured using radioimmunoassay and SNPs (FokI, ApaI, and TaqI) were analyzed by a PCR-RFLP assay. Relevant medical history was collected. RESULTS: About 75 asthmatic (median age: 9.1 years) and 227 healthy children (10.3 years) were studied. In the whole population, the proportion of sufficient, insufficient, and deficient levels of 25OHD were 14.9%, 44%, and 41.1%, respectively. 25OHD sufficiency status was similar in asthmatic and healthy children (p = 0.57). However, the proportion of 25OHD sufficient levels among asthmatics according to the Global Initiative for Asthma treatment steps 2, 3, and 4 was significantly different (8.6%, 16.6%, and 43.7%, respectively, p = 0.046). All patients on step 4 of the treatment (16/16) were heterozygous for the C allele (FokI VDR SNP). There was a lower presence of the C allele among asthmatics in step 2 (30/33), step 3 (16/24), and controls (45/50), p = 0.007, but this significance did not persist after logistic regression. No significant differences in ApaI and TaqI were found. CONCLUSIONS: We found a possible association of vitamin D sufficiency status and FokI C allele with higher requirement of therapy to reach asthma control, suggesting that it may be involved in treatment response. Variations in VDR might also play a role in the 25OHD levels.