DBP variations have an impact on the metabolite of vitamin D, thereby affecting the amount and activity of vitamin D in the β cell which play an important role in insulin secretion. Another possibility is that the association might be Rho-associated protein kinase not due to the vitamin D metabolite. Fatty acids, as one of the ligands of DBP, may also induce β cell abnormalities when it is at a high
level in the pancreas islet.19 As a macrophage-activating factor, DBP is also critical to the immune system. Several cytokines, such as the tumour necrosis factor, could play important roles in insulin sensitivity.4 It is also possible that the association of the DBP polymorphism with T2DM does not result from functional variations in DBP, but is derived from a variation in a closely linked gene on chromosome 4q12.11 Strengths and limitations To the best of our knowledge, this is the first systematic review and meta-analysis to evaluate the association of DBP polymorphisms with T2DM. In this meta-analysis, sensitivity analysis and meta-regression were conducted. In addition, several limitations of this study should also be addressed. First, the sample size was relatively small for stratified analyses, which weakened our conclusions. Therefore, more studies need to be conducted to obtain a more reliable result. Second, T2DM is a complex metabolic disorder caused
by the interaction of multiple genetic and environmental factors; so gene-gene and gene-environment interactions should also be taken into account to conclude a true effect if possible. Third, detailed information at an individual level was lacking in previous studies, so some stratified analyses were not able to be performed. If individual raw data were available, effect induced by age, gender, medication use and other environmental factors (sun exposure, dietary vitamin D intake, etc.) could also be investigated. Fourth, we are unable to control
against publication bias for such a small number of studies. Additionally, results of Genome-wide association study (GWAS) studies were not included because the raw data had not been published. Conclusions In conclusion, this meta-analysis had pooled all the available data related to the DBP polymorphism and T2DM, and indicated that the DBP polymorphism was only moderately associated with an increased susceptibility to T2DM in Asians but not in Caucasians. GSK-3 Therefore, more well-designed and large sample studies are warranted to confirm this conclusion, and to fully understand the mechanism of T2DM. Additionally, prospective cohort studies in combination with analyses of other gene and environment factors are also necessary to explore the true effect of the DBP polymorphism on the risk of T2DM. Supplementary Material Author’s manuscript: Click here to view.(5.6M, pdf) Reviewer comments: Click here to view.