Association between vitamin D receptorBsmI, FokI, andCdx2polymorphisms and osteoporosis risk: an updated meta-analysis

Abstract

<jats:p>Background: Many studies have reported the association between vitamin D receptor (VDR) polymorphism and osteoporosis risk. However, their results were conflicting. Six previous meta-analyses have been published to analyze VDR BsmI, FokI, and Cdx2 polymorphisms on osteoporosis risk. However, they did not evaluate the reliability of statistically significant associations. Furthermore, a lot of new articles have been published on these themes, and therefore an updated meta-analysis was performed to further explore these issues. Objectives: To explore the association between VDR BsmI, FokI, and Cdx2 polymorphisms polymorphisms and osteoporosis risk. Methods: The odds ratios (ORs) and 95% confidence intervals (CIs) were pooled to evaluate the association between VDR BsmI, FokI, and Cdx2 polymorphisms and osteoporosis risk. To evaluate the credibility of statistically significant associations, we applied the false-positive report probabilities (FPRP) test and the Venice criteria. Results: Overall, statistically significantly increased osteoporosis risk was found in Indians and women for VDR FokI polymorphism. Statistically significantly decreased osteoporosis risk was found in West Asians for VDR BsmI polymorphism. However, when we performed an sensitivity analysis after excluding low quality and HWD studies, significantly decreased osteoporosis risk was only found in overall population for VDR BsmI polymorphism. Further, less-credible positive results were identified when we evaluated the credibility of positive results.&amp;lt;/p&amp;gt; Conclusion: These positive findings should be interpreted with caution and indicate that significant association may most likely result from less-credible, rather than from true associations or biological factors on the VDR BsmI and FokI polymorphisms with osteoporosis risk.</jats:p>

Role of the Vitamin D Receptor (VDR) in the Pathogenesis of Osteoporosis: A Genetic, Epigenetic and Molecular Pilot Study

“…Several polymorphisms of the VDR gene which correlate with vitamin D levels have been explored due to their involvement in different phenotypes, including FokI (rs2228570; exon 2; C > T), TaqI (rs731236; exon 9; T > C) and Cdx2 (rs11568820; promoter; G > A) [ 16 , 17 , 18 ]. FokI polymorphism is associated with an increased risk of OP in Asian women [ 19 ] and the TT FokI genotype correlates with high VDR expression in patients with Turner syndrome, supporting the hypothesis that VDR gene variants could modulate its expression pattern [ 7 , 12 , 16 ]. In addition, individual homozygotes for the C allele of the TaqI polymorphism showed a higher OP risk in Saudi and Caucasian populations [ 8 , 20 , 21 ].…”

“…These bone impairments can be either a secondary complication of the pathological status, as in microvascular damage in systemic sclerosis patients, and/or a direct consequence of gene mutation, as in inherited endocrine tumors [ 4 , 5 ]. In this context, several factors involved in OP pathogenesis have been identified, but some of them have not yet been fully characterized, including the role of the vitamin D receptor (VDR) [ 6 , 7 ]. The VDR gene is located on chromosome 12 (12q12–q14) and consists of nine exons encoding for a protein consisting of 427 amino acids [ 8 ].…”

Association of rs4516035 Polymorphism with Osteoporosis in the Southeastern Iranian Population: A Case-Control Study

“…Our findings are somewhat surprising, given that an association between the other SNPs, such as TaqI, BsmI, ApaI, and FokI, was reported in other countries. 20 - 22 …”

“…Our findings are somewhat surprising, given that an association between the other SNPs, such as TaqI, BsmI, ApaI, and FokI, was reported in other countries. [20][21][22] The T allele in rs4516035 uses a start codon at exon 1a, producing the VDRA with 427 residues. The C allele adds two exons (1c and 1d) to the mature mRNA and 50 amino acids to the N-terminal of the protein.…”