rs2282679

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 study examined genetic variants in the vitamin D pathway using GWAS data from 3,686 women of African ancestry (1,657 cases). No significant associations were found between vitamin D pathway variants and breast cancer risk overall or by estrogen receptor status (pathway P > 0.5, SNP-level P adj > 0.2). Mendelian randomization analysis showed no association with genetically predicted 25(OH)D levels (P = 0.23). However, a nonsense variant rs41302073 in TYRP1 (pigment synthesis pathway) showed a 54% increased risk of breast cancer (OR = 1.54, 95% CI = 1.24-1.91, P adj = 0.007), warranting further investigation of non-vitamin D mechanisms.

This Mendelian randomization study of 702 prostate cancer patients investigated whether vitamin D status (as reflected by the GC rs2282679 polymorphism) causally influences prostate cancer progression. The GC rs2282679 SNP (T>G) was not associated with biochemical recurrence (HR 0.91, 95% CI 0.73-1.12), development of metastases (HR 1.20, 95% CI 0.88-1.63), or overall survival (HR 1.10, 95% CI 0.84-1.43), suggesting that vitamin D status plays an unlikely causal role in prostate cancer prognosis.

This retrospective association study of 264 patients with stages II and III colon cancer examined genetic variants in vitamin D modulating genes and their association with time to recurrence (TTR). The GC rs2282679 GG genotype was significantly associated with decreased TTR (HR=3.64, p=0.027) in patients with surgery alone, while CYP2R1 rs10741657 showed a trend toward decreased TTR (HR=1.50, p=0.060). DHCR7 rs12785878 showed no significant association with TTR.

A cohort study of 1,924 very low birth weight preterm infants examined whether genetic predisposition for vitamin D deficiency (based on three SNPs: rs12794714, rs7944926, and rs2282679) was associated with adverse outcomes. The study found no significant associations between low genetic vitamin D level estimates and prematurity complications (IVH, PVL, BPD, NEC, sepsis, ROP), growth parameters, or bone fractures at age 5 years.

Genome-wide association analysis of circulating vitamin D (25(OH)D) levels in 572 Caucasian children with asthma identified SNPs nominally associated with vitamin D at baseline and year 4, with four SNPs replicated in 592 Costa Rican asthmatics (rs11002969, rs163221, rs1678849, rs4864976). Two major previous GWAS findings were replicated: rs2282679 (GC, p<1.9×10⁻¹⁰⁹ in original study) with strongest effect and rs10741657 (CYP2R1, p=3.3×10⁻²⁰) to a lesser degree, but these associations did not consistently replicate across all three populations including 516 Puerto Rican asthmatics.

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.

This study examined whether genetic variants that predict higher 25-hydroxyvitamin D (25(OH)D) levels are associated with reduced multiple sclerosis (MS) risk in 1,655 MS cases and 6,349 controls. SNPs in GC (rs2282679) were significant predictors of 25(OH)D levels but showed no association with MS risk. The CYP2R1 rs10741657 'A' allele was associated with increased 25(OH)D and reduced MS risk among HLA-DR15 negative individuals (OR=0.89, 95% CI: 0.79-1.01) but not HLA-DR15 positive individuals. CYP27B1 rs703842 'C' allele was inversely associated with MS risk, with stronger effects in HLA-DR15 negative (OR=0.79, 95% CI: 0.69-0.90) versus positive individuals (OR=0.91, 95% CI: 0.80-1.04), suggesting vitamin D's protective effect on MS may be attenuated by the HLA-DR15 risk allele.