Association of GC, CYP27B1, and CYP24A1 gene single-nucleotide polymorphisms and copy number variants with recurrent spontaneous abortion

Recurrent spontaneous abortion (RSA) places a heavy burden on female reproductive health. Vitamin D (VD) is involved in multiple pathways of RSA pathogenesis. CYP27B1, CYP24A1, and GC have established roles in VD metabolism; however, the association of their gene single-nucleotide polymorphisms (SNPs) and copy number variants (CNVs) with RSA remains poorly understood. A key innovation of the present study is the comprehensive analysis of both SNPs and CNVs within these genes to elucidate their collective role in RSA. This study enrolled 75 Chinese RSA patients and 83 matched Chinese female controls. We analyzed SNPs, CNVs, and serum levels of VD metabolites, calcium (Ca), and cytokines. Data analysis revealed significant differences between RSA patients and controls in serum levels of 25-hydroxyvitamin D2 (VD2) (adjusted OR 4.282; 95_%CI: 1.789–10.253; p = 0.001), Ca (adjusted OR 77.691; 95_%CI: 5.465–1104.436; p = 0.001), tumor necrosis factor α (TNF-α) (adjusted OR 24.242; 95 % CI: 2.344–250.737; p = 0.007), and CNV profiles (p ≤ 0.001). In patients with RSA, the CYP24A1 rs6068816 TT genotype was associated with both VD (adjusted OR 1.152; 95_%CI: 1.019–1.302; p = 0.023) and VD3 (adjusted OR 1.167; 95_%CI: 1.026–1.328; p = 0.019). CYP27B1 rs4646536 AG and rs10877012 TG were significantly associated with VD (adjusted OR 1.127; 95_%CI: 1.012–1.255; p = 0.030); (adjusted OR 1.129; 95_%CI: 1.015–1.256; p = 0.026), and GC rs705117 CC and rs2282679 TG were significantly associated with Ca (adjusted OR 39.079; 95_%CI: 1.374–1111.236; p = 0.032); (adjusted OR 0.042; 95_%CI: 0.003–0.502; p = 0.012). CYP24A1 and GC gene CNVs showed a significant inverse correlation with IL-6 (p = 0.027) and a positive association with IL-10 (p = 0.019), respectively. Vitamin D pathway gene CNVs are promising biomarkers for developing predictive diagnostic strategies for RSA in Chinese women.