rs4846048

This case-control association study of 277 participants (197 patients with cervical cancer/precancerous lesions, 80 controls) found that MTHFR SNP rs4846048 is associated with elevated cervical cancer risk (AG and G allele frequencies significantly higher in CC vs controls, OR 2.62 for AG genotype). Mechanistically, the study demonstrated through luciferase reporter assays and cell transfection experiments that the rs4846048 A/G alleles promote binding of microRNA-522 (miR-522) to MTHFR's 3'-UTR, and that miR-522 overexpression downregulates MTHFR expression and increases cell viability while decreasing apoptosis in HeLa cells.

This association study screened 57 SNPs from 11 one-carbon metabolism genes in 564 NSCLC patients to identify genetic variants affecting lung cancer prognosis. Key findings included favorable prognostic associations for MTR rs3768160 A>G (HR=0.78, 95% CI 0.62-0.98), MTRR rs2966952 G>A (HR=0.84, 95% CI 0.71-0.99), and DHFR rs1650697 G>A (HR=0.83, 95% CI 0.70-0.99), with unfavorable prognosis for MTHFD1 rs1950902 G>A (HR=1.18, 95% CI 0.99-1.40). Combined analysis of these four SNPs demonstrated a locus-dosage effect on NSCLC survival (P trend = 6.9×10⁻⁵) and identified combined genotypes as an independent prognostic factor.

This candidate gene association study examined five SNPs in the MTHFR gene in 405 Caucasian nuclear families (1,873 individuals) and found significant associations between MTHFR polymorphisms and lean body mass (LBM). rs2066470 (P = 0.0006), rs4846048 (P = 0.0007), and rs3737964 (P = 0.004) were associated with LBM, with rs2066470 explaining 3.67% of LBM variation. BMI associations with rs4846048 (P = 0.009) were mediated through LBM. No associations were found with fat body mass.