rs7968585

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 candidate gene association study examined 141 SNPs in 6 vitamin D metabolism genes (VDR, CYP27B1, CYP24A1, GC, LRP2, CUBN) in 1514 participants from the Cardiovascular Health Study, identifying VDR SNP rs7968585 as significantly modifying the association between low 25-hydroxyvitamin D concentration and composite outcomes (hip fracture, MI, cancer, mortality). Among CHS participants, low vitamin D was associated with hazard ratios of 1.40 (95% CI, 1.12-1.74) for 1 minor allele and 1.82 (95% CI, 1.31-2.54) for 2 minor alleles at rs7968585, versus no association (HR 0.93) in those with 0 minor alleles. Findings were replicated in independent meta-analyses of 3 additional cohorts (n=2727), with rs7968585 showing HRR of 1.22 (95% CI, 1.09-1.36) per additional minor allele.