Association between the vitamin D receptor gene polymorphisms and diabetic nephropathy risk: A meta‐analysis
Accumulating evidence indicates that there is a strong association between individual’s genetic make‐up and predisposition to DN susceptibility.5 Thus, genetic variants for some certain genes can be detected among those individuals at high risk of DN, and may be functioned as biomarkers.10 Vitamin D is an immunoregulatory hormone, and central to the control of bone and calcium homeostasis.11 A non‐linear contribution of serum vitamin D to symptomatic DN occurrence was identified.12 The deficiency of vitamin D is independently associated with DN,13 and is shown to be prevalent in patients with DN and increased in severity with DN progression.14 Vitamin D initiates its biological responses via binding to the vitamin D receptor (VDR). VDR, located on human chromosome 12 (12q12‐q14), is a member of the steroid hormone receptor superfamily and regulates gene expression in a ligand dependent manner.15 VDR is active in almost all tissues that are necessary for the effects of vitamin D. Recent studies suggest that the effect of VDR activation plays a significant role in the development of diabetic kidney disease.16 Several genetic variations have been identified in the VDR gene.18 Among which, ApaI (rs7975232 in intron 8), BsmI (rs1544410 in intron 8), TaqI (rs731236 in exon 9) at the 3′ end, and FokI (rs2228570 in exon 2) at the 5′ end of this gene were the most studied.19
Although several studies have evaluated the association between VDR polymorphisms and DN susceptibility, the results still remain inconclusive. For example, Zhang et al. have found that Bsm I polymorphism of the VDR gene was associated with DN risk in type 2 diabetes patients,20 while Hong et al. showed that there was no association between the Bsm I polymorphism and DN susceptibility in type 2 diabetic subjects.21 In addition, there exists the distributional difference in incidence of DN patients, with increasing prevalence of DN particularly in Asia.22 Given the heterogeneity of the renal lesions and the complex mechanism underlying DN, we conducted the present meta‐analysis to assess all the published articles on this issue to obtain a relatively reliant result.