No association between the vitamin D-binding protein (DBP) gene polymorphisms (rs7041 and rs4588) and multiple sclerosis and type 1 diabetes mellitus: A meta-analysis

Abstract

Background The association between polymorphisms in vitamin D-binding protein (DBP) gene and the risk of multiple sclerosis (MS) and type 1 diabetes mellitus (T1DM) has been investigated in many studies, but the studies showed controversial results. The rationale for this meta-analysis was to determine whether DBP polymorphisms increases the risk of MS and T1DM by pooling data. Methods Potentially relevant studies were searched using GWAS Catalog, PubMed, Embase, CNKI and WANFANG databases up to November 2019. The pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were performed to estimate the associations in a fixed-effects or random-effects model. Results A total of 13 studies were enrolled in this meta-analysis, including eight studies for MS and five for T1DM. The overall results showed that there was no significant association of DBP rs7041 and rs4588 polymorphisms with the risk of MS and T1DM under any genetic model. Similarly, subgroup analysis by ethnicity revealed that no significant association of rs7041 and rs4588 polymorphisms with the risk of MS and T1DM was observed in white or non-white racial groups. Conclusions This meta-analysis provides evidence that DBP rs7041 and rs4588 polymorphisms may not be associated with an increased risk in MS and T1DM. However, these findings need further validation by larger-scale epidemiological studies and genome-wide association studies (GWASs) in different populations.

rs7041 and rs4588 Polymorphisms in Vitamin D Binding Protein Gene (VDBP) and the Risk of Diseases

“…The meta-analysis of the five studies presented showed no association between rs7041 and rs4588 polymorphisms with the risk of T1D [62].…”

“…Langer-Gould et al suggested that these differences cannot be explained by racial/ethnic variations in bioavailable vitamin D [92]. Xin Zhang et al provide evidence that VDBP rs7041 and 4588 polymorphism may not be associated with an increased risk of multiple sclerosis in the meta-analysis [62].…”

Free, bioavailable 25-hydroxyvitamin D levels and their association with diabetic ketoacidosis in children with type 1 diabetes at diagnosis

“…The VDBP allele frequency in our study subjects was similar to previously reported Korean genotyping results ( 19 ), and no significant differences were observed between T1DM and controls. A recent meta-analysis reported no significant association between VDBP polymorphisms and T1DM risk ( 39 ). Because all of our subjects were the same race and the sample size was too small, we could not analyze the role of VDBP polymorphisms in the development of T1DM or DKA.…”

Heritability Estimation of Multiple Sclerosis Related Plasma Protein Levels in Sardinian Families with Immunochip Genotyping Data

“…The missense variant, rs7041, located in the Gc gene and that resulted significantly associated in our analysis with Gc plasma levels, has been consistently found to be associated with serum Gc levels as well as vitamin D levels [ 43 , 63 , 64 ]. This SNP did not result associated with MS in [ 65 , 66 ], but a protective effect of the C allele on MS risk was found in [ 67 ] as this allele was also linked to higher serum vitamin D levels. The intronic variant rs10455872 is located on the lipoprotein(a) ( LPA ) gene, and the G allele has been previously strongly linked to increased plasma lipoprotein(a) [Lp(a)] levels [ 68 ].…”