Risk conferred by FokI polymorphism of vitamin D receptor (VDR) gene for essential hypertension.

BACKGROUND: The vitamin D receptor (VDR) gene serves as a good candidate gene for susceptibility to several diseases. The gene has a critical role in regulating the renin-angiotensin system (RAS) influencing the regulation of blood pressure. Hence determining the association of VDR polymorphisms with essential hypertension is expected to help in the evaluation of risk for the condition. AIM: The aim of this study was to evaluate association between VDRFok I polymorphism and genetic susceptibility to essential hypertension. MATERIALS AND METHODS: Two hundred and eighty clinically diagnosed hypertensive patients and 200 normotensive healthy controls were analyzed for Fok I (T/C) [rs2228570] polymorphism by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) analysis. Genotype distribution and allele frequencies in patients and controls, and odds ratios (ORs) were calculated to predict the risk for developing hypertension by the individuals of different genotypes. RESULTS: The genotype distribution and allele frequencies of Fok I (T/C) [rs2228570] VDR polymorphism differed significantly between patients and controls (χ2 of 18.0; 2 degrees of freedom; P = 0.000). FF genotype and allele F were at significantly greater risk for developing hypertension and the risk was elevated for both the sexes, cases with positive family history and habit of smoking. CONCLUSIONS: Our data suggest that VDR gene Fok I polymorphism is associated with the risk of developing essential hypertension.

Association of gene-gene interaction of TNF-? and VDR loci with hepatitis B virus chronic infection of Han population in North China / 基础医学与临床

Objective To determine potential gene-gene interactions of TNF-? and VDR loci with outcomes of hepatitis B virus(HBV) infection.Methods A total of 391 chronic hepatitis B(HB) patients as a case group and 212 HBV self-limited infected subjects as a control group were recruited to conduct a case-control study.TNF-?-238G/A,-857C/T,-863C/A,VDR-TaqⅠT/C and FokⅠC/T gene polymorphisms were examined by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP).The interactions between TNF-? and VDR genes were analyzed by multiple model.Results There were positive gene-gene interactions between TNF-?-238 GA and FokⅠ CT/CC(ORint=4.04),between-863 CC and-857 CC(ORint=1.26) and between-857 CC and FokⅠ CT/CC(ORint=1.37),respectively,which increase the risk of chronic hepatitis B.There were negative gene-gene interactions between TNF-?-238 GA and-857 CC(ORint=0.92)and between FokⅠ CT/CC and TNF-?-863 CC(ORint=0.95),which decrease the risk of chronic hepatitis B.Conclusion Interaction between TNF-? loci and VDR loci potentially increase the risk of chronic hepatitis B after HBV infection.

Análisis del polimorfismo Bsm I del gen receptor de la vitamina D (VDR) en pacientes venezolanas residentes del estado Zulia con osteoporosis

Resumen. Dentro de los genes implicados en el estudio de la genética de la osteoporosis, el más conocido es el gen receptor de la vitamina D (VDR), estudiado a través de la caracterización del polimorfismo Bsm I. En tal sentido, esta investigación tuvo como objetivo principal analizar el polimorfismo Bsm I del gen de VDR en una muestra de 133 mujeres posmenopáusicas distribuidas en tres grupos: 54 afectadas con osteoporosis, 24 con osteopenia y 55 controles normales para la enfermedad. De las mujeres con osteoporosis 28 presentaron el genotipo BB, asociado en otros países con disminución de la densidad mineral ósea, 20 presentaron el genotipo Bb y 6 el genotipo bb. Del grupo control sólo 11 mujeres presentaron el genotipo BB, 36 mostraron el genotipo heterocigoto Bb y 8 el genotipo bb. La frecuencia de los alelos B y b en la población general analizada resultó de 0,6 y 0,4, respectivamente. El genotipo BB se encontró en un 52% del grupo con osteoporosis y en un 20% en el grupo control normal, siendo estos hallazgos significativos estadísticamente, lo cual sugiere una asociación entre el genotipo BB y la osteoporosis.

Abstract. Among genes implied on the osteoporosis genetics, the most studied gene worldwide is the receptor gene of D vitamin (VDR), through the characterization of Bsm I polymorphism. The main objective of this research was to analyze the Bsm I polymorphism of the VDR gene in a sample of 133 postmenopausal women distributed in three groups: 54 with osteoporosis, 24 with osteopenia and 55 normal controls for the disease. 28 of the women with osteoporosis presented the BB genotype, which is related in others countries to bone mineral density decrease, 20 had the Bb genotype, and 6 the bb genotype. Of the control group only 11 women presented the BB genotype, 36 showed the heterozygote genotype and 8 the bb genotype. The frequencies of the B and b alleles in the analyzed population were 0.6 and 0.4 respectively. The BB genotype was found in 52% of the group with osteoporosis, and in 20% of the control group, these findings are statistically significant, which suggest an association between the BB genotype and osteoporosis.

Study of vitamin-D receptor (VDR) gene start codon polymorphism (Fok I) in healthy individuals from North India.

The vitamin D receptor (VDR) gene Fok I polymorphism represents a strong positional candidate susceptibility gene for different diseases like Prostate cancer, Urolithiasis, Inflammatory bowl disease and Osteoporosis. This genetic variation has also been of great interest due to its possible association with polygenic diseases. Allelic frequencies of the F/f start codon polymorphism of VDR gene vary among populations but there is no data regarding its distribution from India. The present study was carried out to determine the normal distribution of VDR gene Fok I polymorphism by using a PCR-based restriction analysis in unrelated normal healthy individuals from North India. We obtained an allelic frequency of 71.5% and 28.5% for (F) and (f) allele and the percentage of genotypes FF, Ff and ff as 46%, 51% and 3% respectively. Our results suggest that the frequency and distribution of this polymorphism in Indian population is substantially different from other populations and ethenic groups.

The Relationship between Vitamin D Receptor Gene Polymorphisms and the Effect of Hormone Replacement Therapy on Bone Mineral Density in Postmenopausal Korean Women / 대한산부인과학회잡지

OBJECTIVE: to investigate whether vitamin D receptor (VDR) gene polymorphisms are associated with the effect of hormone replacement therapy (HRT) on bone mineral density (BMD) in postmenopausal Korean women. METHODS: The BsmI, ApaI, and TaqI polymorphisms were analyzed by restriction fragment length polymorphism (RFLP) and poly (A) polymorphism by GeneScan and direct DNA sequencing in 304 postmenopausal Korean women who received sequential HRT for 1 year. Serum bone alkaline phosphatase, CrossLaps, osteocalcin and 1,25 (OH)2 vitamin D3 levels were measured by immunoassay and BMD at the lumbar spine and femoral neck by dual energy X-ray absorptiometry before and after HRT of 1 year. RESULTS: The BsmI and TaqI polymorphisms were significantly associated with annual percentage changes in BMD at the lumbar spine. The bb and TT genotype showed a significantly lower percentage changes in BMD of lumbar spine than the Bb and Tt genotype. Annual percentage change in BMD at the lumbar spine was significantly lower in the bT haplotype homozygote women than in women who did not bT haplotype allele, but the bT haplotype genotypes were not distributed differently among HRT-responders and HRT-nonresponders (women who lose more than 3% of bone mass per year). No significant association between annual BMD changes in at all skeletal site and the ApaI or poly (A) polymorphism was observed. There were no significant differences in the 6 month percentage changes in 1,25 (OH)2 vitamin D3 or bone turnover markers among any of the genotypes analyzed. CONCLUSIONS: The VDR bT haplotype allele is associated with the effect of HRT on BMD at the lumbar spine in Korean women.

Relationship between vitamin D receptor gene polymorphism, and bone mineral density in postmenopausal Korean women / 대한산부인과학회잡지

OBJECTIVE: To investigate the relationship between vitamin D receptor (VDR) gene polymorphisms and bone mineral density (BMD) in postmenopausal Korean women, and to evaluate if VDR gene polymorphisms are associated with serum levels of 1,25 (OH)2 vitamin D3 and bone turnover markers METHODS: The BsmI, TaqI, ApaI, and FokI polymorphisms were analyzed by restriction fragment length polymorphism in 443 postmenopausal Korean women. Serum CrossLaps (CTX), bone alkaline phosphatase (BAP), osteocalcin and 1,25 (OH)2 vitamin D3 levels were measured by enzyme linked immunosorbent assay and immmunoassay and BMD at the lumbar spine and proximal femur by dual energy X-ray absorptiometry. RESULTS: BMD at the femoral neck and Ward' triangle in women with the Bb, and Tt genotype (uppercase letters signifying the absence and lowercase letters the presence of the restriction site) was lower than that in women with the bb, and tt genotype respectively. Haplotype analysis showed that BbTt genotype had lower BMD at all skeletal sites than bbtt genotype. No significant association between adjusted BMD at any skeletal site and the FokI or ApaI genotypes was observed. There were no significant associations between the adjusted levels of the bone markers and 1,25 (OH)2 vitamin D3 and single or combined genotypes. CONCLUSION: The VDR gene BsmI, and TaqI polymorphisms are genetic factors which may affect BMD at the lumbar spine and proximal femur in postmenopausal Korean women, but does not affect serum levels of 1,25 (OH)2 vitamin D3 and bone turnover markers.