Effect of vitamin D3 supplementation on 25 OHD plasma levels in the presence of VDR gene polymorphisms / Efecto de la suplementación con vitamina D3 en los niveles plasmáticos de 25 OHD, en presencia de polimorfismos del gen VDR

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.

Vitamin D Receptor Gene TaqI, BsmI and FokI Polymorphisms in Korean Patients with Tuberculosis

BACKGROUND: The active metabolite (1, 25-dihydroxycholecalciferol) of vitamin D (25-hydroxycholecalciferol) leads to activation of macrophages and deficiency of vitamin D seems to be involved in the risk of tuberculosis. The effects of vitamin D are exerted by interaction with the vitamin D receptor (VDR) and may be influenced by polymorphism in the VDR gene. In this study, variation in the VDR gene was investigated in Korean population with tuberculosis. METHODS: We typed three VDR polymorphisms of restriction endonuclease sites for TaqI, BsmI and FokI in 155 patients with tuberculosis and 105 healthy volunteers. RESULTS: The frequencies of FokI genotypes determined from TB patients were 29.13% for FF, 56.31% for Ff, and 14.56% for ff. We observed 1.4-fold increased prevalence of the Ff genotype in TB patients compared with normal healthy groups (p=0.0857). However, there was no significant association between the genotype groups, TB patient and normal control, for FokI polymorphism. There was also no significant association between VDR gene and tuberculosis in another polymorphism (BsmI and TaqI). CONCLUSION: Three polymorphisms (TaqI, BsmI and FokI) in the VDR gene do not appear to be responsible for host susceptibility to human tuberculosis in Korean population.

Vitamin D Receptor Gene TaqI, BsmI and FokI Polymorphisms in Korean Patients with Tuberculosis

BACKGROUND: The active metabolite (1, 25-dihydroxycholecalciferol) of vitamin D (25-hydroxycholecalciferol) leads to activation of macrophages and deficiency of vitamin D seems to be involved in the risk of tuberculosis. The effects of vitamin D are exerted by interaction with the vitamin D receptor (VDR) and may be influenced by polymorphism in the VDR gene. In this study, variation in the VDR gene was investigated in Korean population with tuberculosis. METHODS: We typed three VDR polymorphisms of restriction endonuclease sites for TaqI, BsmI and FokI in 155 patients with tuberculosis and 105 healthy volunteers. RESULTS: The frequencies of FokI genotypes determined from TB patients were 29.13% for FF, 56.31% for Ff, and 14.56% for ff. We observed 1.4-fold increased prevalence of the Ff genotype in TB patients compared with normal healthy groups (p=0.0857). However, there was no significant association between the genotype groups, TB patient and normal control, for FokI polymorphism. There was also no significant association between VDR gene and tuberculosis in another polymorphism (BsmI and TaqI). CONCLUSION: Three polymorphisms (TaqI, BsmI and FokI) in the VDR gene do not appear to be responsible for host susceptibility to human tuberculosis in Korean population.

Association of vitamin D receptor gene FokI polymorphism with systemic lupus erythematosus / 中华风湿病学杂志

Objective To determine the distribution of vitamin D receptor(VDR)gene FokI polymorphism in systemic lupus erythematosus(SLE)and the association with SLE in Chinese Han patients. Methods Genomic DNA from 271 Chinese SLE patients and 130 sex and ethnically matched controls were typed for VDR FokI polymorphism by polymerase chain reaction restriction fragment length polymorphism(PCRRFLP). Clinical characteristics were analyzed between different FokI genotypes. ResuIts Fokl allelic frequencies were not in Hardy-Weinberg equilibrium(χ2=7.288, P=0.026 for the control group and χ2=7.883, P=0.019 for the SLE patient group). The distribution frequencies of allelic gene F and f were 48.8% and 51.2% in the controls respectively, 60.9% and 39.1%(χ2=10.39, P=0.001)in the SLE patients respectively. The relative risk of allelic gene F developing to SLE was 1.630(95%CI=1.210～1.196, χ2=10.39, P=0.001). The distribution frequencies of genotypes homozygote FF, heterozygote Ff and homozygote ff were 25.4%, 46.9%,and 27.7% in the controls respectively; 42.8%(χ2=11.417, P=0.001), 36.2%(χ2=4.251, P=0.039)and 21.0% (χ2=2.187, P=0.139)in SLE respectively. The relative risk of homozygote FF and heterozygote Ff genotypes was 2.200(95%CI=1.385～3.493, χ2=11.417, P=0.001)and 0.641(95%CI=0.419～0.979, χ2=4.251, P=0.039)respectively. Furthermore, no significant difference was observed in SLE patients carrying different FokI genotypes in SLE disease activity index(SLEDAI)(P=0.382), symptoms and signs, while significant difference was observed in SLE patients carrying heterozygote Ff genotypes involved in serositis(P=0.001). Elevated frequencies of heterozygote Ff genotypes were observed in patients with anti-dsDNA antibody, anti-Sm antibody and anti-histone antibody respectively(P=0.001, P=0.047, P=0.001 respectively). However, the incidence rate of malar rash was lower than other genotypes in heterozygote Ff genotypes(P=0.005).Conclusion There is association between the VDR gene FokI polymorphism and the susceptibility to systemic lupus erythematosus in Han population of southern China. Allelic gene F, homozygote FF and heterozygote Ff genotypes increase the susceptibility to systemic lupus erythematosus. Otherwise, heterozygote Ff genotype is more frequently involved in serositis and generates anfi-dsDNA antibody, anti-Sm antibody and anti-Histone antibody.

Frequency of fokI and taqI polymorphism of vitamin D receptor gene in Indian population and its association with 25-hydroxyvitamin D levels.

BACKGROUND: The VDR protein is at the centre of the vitamin D endocrine system, a complex physiological system with substantial feedback regulatory mechanisms involved in maintaining serum calcium and 1, 25 dihydroxy vitamin D3. Variations in VDR gene are shown to have implications in several diseases and have also been implicated as an important genetic factor affecting bone mass. AIM: To determine the frequency of Fok I and Taq I variants in healthy Indian individuals and its association with 25-OH-Vitamin D levels. SETTINGS AND DESIGN: Blood samples were collected from 143 unrelated normal individuals (Male-84 and Female-59) and their genotypes determined. MATERIALS AND METHODS: After amplification by polymerase chain reaction, each polymorphism was genotyped by restriction fragment length polymorphism. For 100 normal healthy individuals 25-hydroxyvitamin D estimation was done using DiaSorin kit method. STATISTICAL ANALYSIS: Graph pad software was used to calculate the P values from the Chi-square. RESULTS: Out of 143 samples analyzed for FokI and TaqI polymorphisms the following genotypic frequency was obtained FF 59%, Ff 36%, ff 5% and TT 49%, Tt 43%, tt 8% respectively. CONCLUSIONS: Results indicate that the distribution of the polymorphic loci Fok I and Taq I vary considerably not only in different populations, but also within India. Furthermore, when the genotypes were analyzed with respect to 25-OH-Vitamin D levels, a significant association was seen for the Taq 1 SNP but not with the Fok I.