rs2853741

This family-based association study examined 14 folate pathway genes using 89 SNPs in 445 NSCLP families (317 non-Hispanic White, 128 Hispanic) to identify genetic variants contributing to nonsyndromic cleft lip and palate. Evidence for association was found with SNPs in NOS3 and TYMS in the non-Hispanic White group (rs2373929/NOS3, rs502396/TYMS, and others), and with MTR, BHMT2, MTHFS, and SLC19A1 in the Hispanic group (rs1422086/BHMT2, rs2115540/MTHFS significant after Bonferroni correction). Multiple gene-gene interactions were detected, with CBS and MTHFD1 showing the most extensive interactions. Significant interactions were also found between several SNPs and maternal smoking and one SNP (rs651646/FOLR2) with offspring sex.

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.