rs4588

This case-control study of 288 Spanish RLS patients and 325 controls examined vitamin D metabolism genes and serum vitamin D levels. Serum 25-hydroxyvitamin D levels were significantly higher in RLS patients (21.94 ng/mL vs 18.63 ng/mL, p=0.0002), but seven SNPs in VDR and GC genes showed no association with RLS risk. However, RLS patients carrying the rs7975232CC genotype had higher frequency of response to GABAergic drugs.

This case-control association study of 815 Chinese pregnant women identified five SNPs in the GC (vitamin D-binding protein) gene significantly associated with serum 25-hydroxyvitamin D concentration: rs17467825, rs4588, rs2282679, rs2298850, and rs1155563. Mean 25(OH)D level was 15.67±7.98 ng/mL with 75% prevalence of deficiency. An XGBoost model incorporating these SNPs plus environmental factors achieved AUC 0.828 for predicting 25(OH)D deficiency risk. The study suggests maternal vitamin D deficiency may increase macrosomia risk (12 of 16 macrosomic infants had deficient mothers).

This randomized, double-blind, placebo-controlled trial examined associations between SNPs in calcium and vitamin D-related genes and bone biomarkers in 748 young military trainees. The study found that rs7041 (DBP gene) was associated with higher 25OHD (β=4.46, p=1.97E-10) and rs2228570 (VDR gene) was associated with lower P1NP (β=-4.83, p=0.04) and osteocalcin. A composite genetic risk score combining rs7041 and rs1544410 predicted differential responses to calcium and vitamin D supplementation during intensive military training.

This study evaluated 25(OH) vitamin D3 levels and associated SNPs in 97 newly-diagnosed, intensively-treated AML patients. Low vitamin D levels were associated with worse relapse-free survival (RFS) and overall survival (OS). The VDR SNP rs10783219 (T allele) was significantly associated with lower complete remission rates (p=0.0442), shorter RFS (p=0.0058), and shorter OS (p=0.0011); this SNP remained significant in multivariate analysis. Two additional SNPs in the GC gene (rs4588 and rs2762934) showed associations with vitamin D levels but did not retain significance after multiple test correction.

This study examined 89 genetic sequence variants in six vitamin D metabolism pathway genes (VDR, GC, CYP24A1, CYP27A1, CYP27B1, CYP2R1) in 522 early-stage head and neck cancer patients to assess associations with overall survival and second primary cancer risk. GC rs4588 and CYP2R1 rs10500804 were associated with lower serum vitamin D levels. CYP24A1 rs2296241 (aHR 1.23, p=0.05) was significantly associated with worse overall survival, while CYP2R1 rs1993116 (aHR 0.59, p=0.001) was protective against second primary cancer, independent of serum vitamin D levels.

A retrospective association study of 206 chronic hepatitis C patients examining whether vitamin D binding protein (GC) gene polymorphisms (rs7041, rs4588) and baseline vitamin D levels predict antiviral response. In difficult-to-treat HCV genotypes, patients with vitamin D >20 ng/mL and the GC wildtype (WT+) diplotype had significantly higher sustained viral response (SVR) rates (65.5% vs 24.0%, p=0.003), with multivariate OR=4.52 (p=0.015) for vitamin D >20 + GC WT+. IL-28B rs12979860 was confirmed as a strong independent predictor of SVR across all genotypes.

This study examined associations between common variants in GC, CYP2R1, and NADSYN1/DHCR7 genes and plasma 25-hydroxyvitamin D levels in 3,210 Chinese Hans. Six variants showed significant associations with lower vitamin D levels: GC-rs4588 (β = -0.076 per risk-allele, P = 1.3 × 10⁻²⁶), GC-rs2282679 (β = -0.072, P = 4.9 × 10⁻²⁴), GC-rs7041, GC-rs1155563, NADSYN1/DHCR7-rs3829251 (β = -0.036, P = 4.7 × 10⁻⁵), and DHCR7-rs1790349 (β = -0.036, P = 5.7 × 10⁻⁵). Conditional analyses indicated that GC-rs4588 and GC-rs2282679 drive the associations at the GC locus in Chinese populations.

Population-based association study of vitamin D binding protein (DBP) gene variants rs7041 (Glu416Asp) and rs4588 (Thr420Lys) in 6,181 elderly Caucasians from the Rotterdam Study. DBP haplotype 1 was associated with increased serum 25-(OH)D3 levels (P=3×10⁻⁴) and a 47% increased fracture risk in subjects with low dietary calcium intake (HR 1.47, 95% CI 1.06-2.05). Gene-gene interaction was observed between DBP and VDR haplotypes (interaction P=0.015), with combined carriers showing 33% increased fracture risk (HR 1.32, 95% CI 1.07-1.61).