Association of intronic variants (Apal and Bsml) of vitamin D receptor gene with uterine leiomyoma among North Indian women

Abstract

Background: Understanding the genetic factors involved in the Uterine Leiomyoma (UL) development is crucial for exploring the complexities of UL disorders. This study aimed to examine genetic association between UL incidence and intronic polymorphisms of vitamin D receptor gene in north Indian population. Methodology: Total 200 subjects (100 healthy women and 100 with uterine leiomyomas) of age- and gender-matched control subjects, were genotyped for BsmI (rs1544410) and ApaI (rs7975232) polymorphisms in the VDR gene using TETRA ARMS PCR, followed by Sanger sequencing validation. Levels of VDR mRNA and vitamin D were also assessed through quantitative real-time PCR and ELISA respectively. The association of these variants with leiomyomas was analyzed, along with clinico-pathological (obesity) association. Results: ApaI revealed a significant association with UL, especially for the TG genotype (OR = 2.38; 95 % CI, 1.26–––4.51; p = 0.003). In a similar manner, ApaI is associated with an increased risk for UL with all three genetic models. Comparing VDR ApaI polymorphism between obese and non-obese patients revealed that AC genotype was significantly (OR = 3.71; 95 % CI, 1.53––9.11; p = 0.002) associated with a reduced risk of UL in non-obese patients. The expression of VDR mRNA was two times lower in patients with UL (p < 0.001), along with decreased serum vitamin D levels (p < 0.001). A significant association was also observed between VDR ApaI variant with reduced mRNA expression, vitamin D level and obesity. However, no associations were observed among Bsm1 VDR genotypes and ULs. Conclusion: This study found significant association between the VDR intronic ApaI polymorphism (rs7975232) and the incidence of UL. This VDR variant showed significant association with reduced VDR mRNA expression and serum vitamin D levels in UL patients. However, no significant association was observed between BsmI VDR polymorphism (rs1544410) and UL in North Indian women. © 2025 Elsevier B.V.