The impact of MTHFR and VDR polymorphisms on endometriosis susceptibility: Insights from a systematic review and meta-analysis

The VDR and MTHFR polymorphisms have been linked to many gynecological and obstetrical diseases. However, there is still a pressing need for a systematic review and meta-analysis to synthesize the current evidence on the association between these variants and endometriosis risk. English and Chinese literature databases were systematically retrieved to find relevant research published up to August 1, 2024. The meta-analytic calculations were implemented in the R language 4.4.1 environment. The odds ratios (ORs) with the corresponding 95 % confidence intervals (95 % CIs) were estimated to assess the magnitude of the effect. In total, 26 datasets comprising 9300 subjects were included. The pooled estimate demonstrated a significant association between the MTHFR C677T polymorphism and endometriosis susceptibility in the allele model (OR: 1.41, 95 % CI: 1.07–1.86, P = 0.01), homozygote model (OR: 2.09, 95 % CI: 1.56–2.79, P < 0.01), dominant model (OR: 1.48, 95 % CI: 1.06–2.07, P = 0.02), and recessive model (OR: 1.81, 95 % CI: 1.38–2.37, P < 0.01). However, the meta-analysis for the MTHFR A1298C polymorphism and the VDR FokI, TaqI, ApaI, and BsmI polymorphic variants did not find statistical significance. In conclusion, this meta-analysis suggests that the MTHFR C677T polymorphism might play a role in developing endometriosis disease. Meanwhile, further large-scale validations that consider multiple factors are warranted to confirm this finding.