BsmI, TaqI, ApaI and FokI Polymorphisms in the Vitamin D Receptor (VDR) Gene and the Risk of Osteoporosis: A Meta‐Analysis

Abstract

A meta-analysis regarding BsmI, TaqI, ApaI and FokI polymorphisms in the vitamin D receptor (VDR) gene and their associations with osteoporosis in females is reported. The meta-analysis involved 14, seven, seven and three studies for BsmI, TaqI, ApaI and FokI polymorphisms, respectively. The studies were association studies with osteoporotic cases and controls free of osteoporosis that provided the genotype distribution of individual cases and controls. For the BsmI polymorphism, the allele contrast b vs. B showed heterogeneity among studies (p < 0.01, I2 > 50%) and the random effects (RE) pooled odds ratio (OR) was non-significant: 0.94 [95% confidence interval (CI) 0.63–1.38]. Caucasians, postmenopausal cases and studies with WHO diagnostic criteria showed no association under any genetic contrast. However, in East Asians, the OR for the dominant model [fixed effects OR = 0.14 (95% CI 0.04–0.50) and RE OR = 0.16 (95% CI 0.03–0.84)] was significant, indicating prevention. Overall, for the TaqI, ApaI and FokI polymorphisms, the allele contrast showed heterogeneity and the pooled RE ORs were non-significant [OR = 1.06 (95% CI 0.71–1.60), OR = 0.99 (95% CI 0.72–1.37) and OR = 1.17 (95% CI 0.76–1.80), respectively]. The allele contrast for Caucasians, East Asians, postmenopausal cases and studies with WHO diagnostic criteria showed no association for TaqI, ApaI, and FokI. The allele contrast of homozygotes, and the recessive and dominant models the results followed the same pattern as the allele contrast. Therefore, the relationship between the VDR polymorphisms and osteoporosis remains an unresolved issue and other probable genetic-environmental risk factors interacting with the above polymorphisms should be investigated.

Vitamin D Receptor FokI Gene Polymorphism Predicted Poor Response to Treatment in Chronic HCV Genotype 4

“…[28,29] All our HCV-4 patients had suboptimal vitamin D levels with the majority being severely deficient (86%). Possible explanations for the association of HCV with vitamin D deficiency have included decreased 25-alpha hydroxylation in the liver, HCV may have the ability to directly suppress 25-alpha hydroxylation through inducing cytokines and oxidative stresses, and a recent study has shown that HCV alters lipid metabolism directly reducing production of 7-dehydrocholesterol, the precursor of endogenouslyproduced vitamin D. [30,31] The independent effect of HCV on vitamin D levels is strongly supported by our finding of the remarkable improvement in vitamin D levels after successful eradication of HCV and its persistence in non-responders.…”

The combinations of polymorphisms in vitamin D receptor, osteoprotegerin and tumour necrosis factor superfamily member 11 genes are associated with bone mineral density

“…In the GENOMOS study, no association of BsmI-ApaI-TaqI(VDR) haplotype with any osteoporotic phenotype was found, whereas Cdx2(VDR) was associated with risk of vertebral fracture (Uitterlinden et al 2006). In FokI(VDR), no association with BMD has been found (Uitterlinden et al 2006, Zintzaras et al 2006.…”

“…The VDR gene is one of the most widely studied osteoporosis-related genes and numerous genetic association studies have yielded conflicting results (Thakkinstian et al 2004, Fang et al 2005, Zintzaras et al 2006. For BsmI(VDR), the metaanalysis has shown contradictory results in BMD-fn (Cooper & Umbach 1996, Gong et al 1999, Thakkinstian et al 2004).…”

“…The outbreak of genetic association studies on osteoporosis started with the reported association between VDR alleles and BMD (Morrison et al 1994). Numerous association studies have been performed on the VDR gene and BMD showing conflicting results (Thakkinstian et al 2004, Fang et al 2005, Zintzaras et al 2006. In a prospective multicentre large-scale association study involving 26 242 participants, only the Cdx2 polymorphism in the VDR gene was found to be associated with the risk of vertebral fractures (Uitterlinden et al 2006).…”

Maternal gene polymorphisms involved in folate metabolism and risk of Down syndrome offspring: a meta-analysis

“…The meta-analysis consisted of the main (overall) analysis, which includes all available data, subgroup analyses by ''race,'' and sensitivity analysis, which examines the effect of excluding specific studies Zintzaras et al 2006d). The distribution of the genotypes in the control group was tested for HardyWeinberg equilibrium (HWE) using an exact test (Weir 1996).…”