ABSTRACT Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disorder influenced by genetic and environmental factors. Vitamin D deficiency and vitamin D receptor (VDR) gene polymorphisms are suggested to modulate immune dysregulation in SLE. This study aimed to investigate the association of VDR polymorphisms ( BsmI , ApaI , TaqI and FokI ), serum 25‐hydroxyvitamin D 25‐OH vitamin D levels and clinical phenotypes in Indian SLE patients. A hospital‐based case–control study was conducted on clinically diagnosed SLE patients ( n = 297) fulfilling American College of Rheumatology (ACR) criteria and healthy controls ( n = 100). Serum 25‐OH vitamin D levels, autoantibody profile and complement components were evaluated by immunofluorescence, enzyme‐linked immunosorbent assay (ELISA) and nephelometry. Genotyping for VDR polymorphisms BsmI (rs1544410) B/b, ApaI (rs7975232) A/a, TaqI (rs731236) T/t and FokI (rs2228570) F/f was performed using polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP). Data were statistically analysed using chi‐square tests, logistic regression and correlation analysis. The median age at evaluation in SLE patients was 29 years, with a female predominance (91.9%). Median serum 25‐OH vitamin D levels were 30.4 ng/mL, with lower levels observed in patients with arthritis ( p = 0.012), neurological involvement ( p = 0.015) and active disease ( p = 0.025). Serum 25‐OH vitamin D inversely correlated with disease activity ( r = −0.127, p = 0.032), anti‐cardiolipin antibody (ACLA) immunoglobulin G (IgG) ( p < 0.001) and anti‐phospholipid antibody (APLA) IgG ( p = 0.030). Among VDR polymorphisms, BsmI b allele conferred reduced disease risk (odds ratio OR = 1.85, p < 0.001). TaqI genotypes (Tt: OR = 2.29 and tt: OR = 6.48, p < 0.05) and t allele (OR = 2.15, p < 0.001) and FokI genotypes (Ff: OR = 4.13 and ff: OR = 3.14, p <0.05) were strongly associated with increased susceptibility to SLE. ApaI variants were significantly associated with alopecia, haematological manifestations, disease activity and low complement component 3 (C3) levels, whereas BsmI and FokI polymorphisms were associated with neurological manifestations ( p < 0.05). Vitamin D receptor gene (VDR gene) polymorphisms may contribute to phenotypic variability and immune dysregulation in Indian SLE patients, suggesting that gene–environment interactions between vitamin D status and VDR variants may influence SLE susceptibility and clinical heterogeneity.
Pawaskar et al. (2026) studied this question.