Association of vitamin D receptor genetic polymorphisms with the risk of infertility: a systematic review and meta-analysis

Abstract

Abstract Background The causes of infertility have remained an important challenge. The relationship between VDR gene polymorphisms and infertility has been reported, with controversial findings. Objective and rationale We aimed to determine this relationship by conducting a systematic review and meta-analysis. Search methods The study was started with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) declaration and the final draft was registered as a protocol in PROSPERO (ID: CRD42023416535). The international electronic databases including PubMed (Medline), Scopus, Web of Sciences, and Cumulative Index to Nursing and Allied Health Literature (CINHAL) were searched until January 30, 2023, by using appropriate keywords. The quality of the final studies was assessed using the NOS Checklist for case–control studies. The odds ratios (ORs) for each of the genetic models were pooled, and a subgroup analysis based on geographical region and types of infertility was carried out by the MetaGenyo online tool. Outcomes Case–control studies including 18 and 2 studies about infertility in women and men, respectively, and 4 miscarriage studies were entered into the meta-analysis. The VDR gene TaqI polymorphism was associated with infertility susceptibility in women in the allele contrast [OR = 1.2065, 95% CI (1.0846–1.3421); P = 0.0005], Recessive model [OR = 1.3836, 95% CI (1.1197–1.7096); P = 0.002], Dominant model [OR = 1.2146, 95% CI (0.0484–1.4072); P = 0.009], Homozygote [OR = 1.4596, 95% CI (1.1627–1.8325); P = 0.001], and TT vs. Tt [OR = 1.2853, 95% CI (1.0249–1.6117); P = 0.029. ApaI and FokI gene polymorphisms were found to be significantly protective SNPs against women and men infertility in the Dominant model [OR = 0.8379, 95% CI (0.7039- 0.9975); P = 0.046] and Recessive model [OR = 0.421, 95% CI (0.1821–0.9767); P = 0.043], respectively. Sub-group meta-analysis showed a protection association of ApaI in dominant [OR = 0.7738, 95% CI = 0.6249–0.9580; P = 0.018] and AA vs. aa [OR = 0.7404, 95 CI% (0.5860–0.9353) P = 0.011725] models in PCOS subgroup, however, a negative association with idiopathic infertility was found in AA vs. Aa [OR = 1.7063, 95% CI (1.1039–2.6375); P = 0.016187] and Aa vs. aa [OR = 0.6069, 95% CI (0.3761–0.9792); P = 0.040754]. TaqI SNP was significantly associated with infertility in the African population and BsmI was associated with the disease mostly in the Asian population. Conclusion This meta-analysis showed that the TaqI polymorphism may be linked to women’s infertility susceptibility. However, ApaI and FokI might be the protective SNPs against infertility in Women and men, respectively.