Vitamin D receptor gene polymorphisms and the risk of the type 1 diabetes: a meta-regression and updated meta-analysis

Abstract

Background: The association between the polymorphisms in the vitamin D receptor (VDR) gene and the risk of type 1 diabetes mellitus (T1DM) has been evaluated in several studies. However, the findings were inconclusive. Thus, we conducted a meta-analysis to comprehensively evaluate the effect of VDR gene polymorphisms on the risk of T1DM. Methods: All relevant studies reporting the association between VDR gene polymorphisms and susceptibility to T1DM published up to May 2020 were identified by comprehensive systematic database search in ISI Web of Science, Scopus, and PubMed/MEDLINE. Strength of association were assessed by calculating of pooled odds ratios (ORs) and 95% confidence intervals (CIs). The methodological quality of each study was assessed according to the Newcastle-Ottawa Scale. To find the potential sources of heterogeneity, meta-regression and subgroup analysis were also performed. Results: A total of 39 case-control studies were included in this meta-analysis. The results of overall population rejected any significant association between VDR gene polymorphisms and T1DM risk. However, the pooled results of subgroup analysis revealed significant negative and positive associations between FokI and BsmI polymorphisms and T1DM in Africans and Americans, respectively. Conclusions: This meta-analysis suggested a significant association between VDR gene polymorphism and T1DM susceptibility in ethnic-specific analysis.

Variants in the VDR Gene May Influence 25(OH)D Levels in Type 1 Diabetes Mellitus in a Brazilian Population

“…In the pairwise comparisons between T1DM and Europeans, there were no differences in allelic and genotypic frequencies of VDR polymorphisms, highlighting the similarity of the studied group with the European population. However, one of these polymorphisms (rs2228570) has been previously associated with decreased risk of T1DM in Europeans [ 43 ], but not in our population.…”

“…The reasons for these discrepant results might be different allelic and genotypic distribution between the populations, as well as environment–gene interactions in the development of T1DM [ 36 , 42 ]. Indeed, in the meta-analyses by Zhai et al (2020) [ 43 ] and Tizaoui et al (2014) [ 44 ] there was no statistical evidence of overall association between VDR polymorphisms and T1DM, but when these analyses were subdivided by ethnicity, the association was found.…”

Genotype Distribution of Vitamin D Receptor Polymorphisms among Indonesian Patients with Chronic Hepatitis B

“…Vitamin D is a fat soluble hormone that has important roles as immune modulator. Epidemiological studies suggest association between vitamin D deficiency and higher incidence of autoimmune diseases (9), cancer (10), metabolic (11) and inflammatory diseases including infection with HBV (12,13). The cellular actions of vitamin D are mediated by vitamin D receptors (VDR), a superfamily of nuclear transcription factor that is expressed in many cell types including various immune cells such as antigen-presenting cells, T cells, B cells and monocytes (14).…”

Vitamin D Receptor gene polymorphisms and susceptibility to type 2 diabetes: evidence from a meta-regression and meta-analysis based on 47 studies

“…Of them, polymorphisms of ApaI, BsmI, and TaqI are located in the 3′-end of VDR gene which lead to silent mutation associated with increased VDR mRNA stability. In contrast, FokI SNP is located in the start codon resulting protein with shorter size, the shorter form of the protein (424amino acid) is more active than the long form (427amino acid) [18][19][20][21]. So far, several studies investigated the potential roles of these common SNPs in T2D but results are conflicting; therefore, here we conducted an updated meta-analysis with the aim of providing a much more reliable conclusion on the significance of the associations.…”