Association between Vitamin D receptor gene polymorphism and the risk of Multiple Sclerosis: Systematic review and meta-analysis

Abstract

Background The association between the vitamin D receptor ( VDR ) gene polymorphism and the risk of Multiple sclerosis (MS) has been evaluated in several studiese. However, the findings were inconsistent and inconclusive.Methods All relevant studies reporting the association between the FokI (rs2228570) or/and TaqI (rs731236) or/and BsmI (rs1544410) or/and ApaI (rs7975232) polymorphisms of the VDR and susceptibility to multiple sclerosis published up to September 2019 were identified by comprehensive systematic database search in web of science, Scopus, and PubMed.Results A total of 30 case–control studies were included in this meta-analysis. The overall results suggested a significant association between TaqI gene polymorphism and MS risk under heterozygote contrast (OR = 1.27, 95%CI = 1.01–1.59, REM). Moreover, the pooled results of subgroup analysis decline presence of significant association under all defined genotype model. In subgroup analysis, BsmI gene polymorphism was associated with increased risk of MS under the recessive model in Asian population. In other hand, ApaI gene polymorphism was associated with decreased risk of MS under recessive and homozygote contrast (aa vs AA) models in Asian population.Conclusions This meta-analysis suggested a significant association between TaqI gene polymorphism and MS susceptibility. Furthermore, BsmI gene polymorphism was associated with an increased risk of MS in Asian population. In contrast, ApaI gene polymorphism was associated with a decreased risk of MS in Asian population. Future large scale studies on gene–environment and gene– gene interactions are required to estimate related risk factors and assist early diagnosis of patients at high risk for MS.

Chemokines in hyperthyroidism

“… IL-23 IL-23A gene could be a genetic risk marker in Han Chinese population [72] . IL-6 A significant association between the IL6 -174 G/C polymorphism and the risk for GD [73] . TNF-α The promoter SNP rs1800629 within the TNF-α gene is associated with increased risk for developing GD [74] .…”

“…The association between IL-6 -174 G/C polymorphism and GD have been investigated by various studies, with discordant results. A meta-analysis was conducted to evaluate such association, and included 4 case-control studies with 554 GD cases and 1201 healthy controls [73] . In the combined analysis, a significant association between the IL-6 -174 G/C polymorphism and the risk for GD in dominant model (OR = 1.39, 95% CI: 1.07–1.80), recessive model (OR = 2.75, 95% CI: 1.01–7.55) and homozygote contrast model (OR = 3.25, 95% CI: 1.1–9.58) was shown [73] .…”

Changes in serum hepcidin according to thyrometabolic status in patients with Graves’ disease

“…Moreover, a positive correlation was found between fT3 and IL-6 (r = 0.35, P < 0.025) as well as between TRAb and IL-6 (r = 0.5, P < 0.003) (20). Additionally, polymorphisms in the IL-6 gene were found to be correlated with GD predisposition (21). It may be presumed that IL-6 overproduction in patients with GD stimulates the JAK2-STAT3 pathway to synthesize hepcidin, which consequently affects iron homeostasis and haematological parameters (12,22).…”

Graves’ disease: introducing new genetic and epigenetic contributors

“…It seems that IL-6 plays a substantial role in GD, for example, a considerable association of IL6-174 G/C polymorphism and also the increased risk of GD in dominant, recessive, and homozygote contrast models have been reported and confirmed by some meta-analysis data (Imani et al 2017). Moreover, it has been demonstrated that rs1800795 of IL-6 can increase susceptibility for GD (Tu et al 2017).…”

“…A combination of genetic, epigenetic, and environmental factors can account for autoimmune responses against the thyroid gland (Imani et al 2017). These responses are limited to lymphocytic infiltration and autoantibodies targeting thyroid antigens, such as TSHR, thyroglobulin (TG), and thyroid peroxidase (TPO).…”