FokI as a genetic factor of intervertebral disc degeneration: A PRISMA-compliant systematic review of overlapping meta-analyses

The association of FokI (r52228570), a polymorphism of the vitamin D receptor gene, with intervertebral disc degeneration (IDD) has been investigated in a multitude of studies. However, conflicting results of these studies led to emergence of several meta-analyses over the past few years. Despite the increased statistical power, these meta-analyses have failed to provide uniform and conclusive data on the relationship of FokI with IDD. The aim of this study was to present a comprehensive review based on the most up-to-date meta-analyses on the association of FokI with IDD. A comprehensive search of all major databases was conducted to identify meta-analyses investigating relation between Fold and IDD. No date or language restrictions were applied. The Jadad decision algorithm was utilized to evaluate included meta-analyses and identify the one providing the best evidence. A total of 7 meta-analyses (n = 2580 original patients), that included six to ten case control studies, analyzed the association of FokI polymorphism with IDD. The meta-analysis of the highest quality supported the notion that overall there is no statistically significant association between FokI polymorphism and IDD. However, the authors showed that Caucasians have a reduced risk of IDD and Hispanics have an increased risk of IDD in the dominant and dominant/homozygous/heterozygous models of FokI polymorphism. While currently there is no evidence of an association between FokI polymorphism and IDD in the general population, ethnic predisposition has been shown. (C) 2018 Elsevier Ltd. All rights reserved.