rs12482346

A family-based association study of 610 meningomyelocele cases (329 trios and 281 duos) across folate transport genes identified 10 SNPs associated with neural tube defects. Key findings include rs13908 in FOLR2 (p=0.0002, OR=0.14), three linked variants in FOLR3 (rs7925545, rs7926875, rs7926987), and two in SLC19A1 (rs1888530, p=7.28E-05, OR=0.26; rs3788200, p=0.0195, OR=0.62), suggesting rare alleles confer protection against meningomyelocele risk.

This case-control study examined folate pathway gene variants in 121 DS-AVSD cases and 122 DS controls (no CHD). Tag SNPs in MTHFR, MTR, MTRR, CBS, and SLC19A1 were genotyped. SLC19A1 showed significant gene-level association with atrioventricular septal defect (P=0.01), with multiple tag SNPs nominally associated (OR 1.08-1.72). All significant SLC19A1 SNPs showed strong LD (r²≥0.80) with the nonsynonymous variant rs1051266 (c.80A>G, p.H27R). MTHFR c.1298A was over-transmitted to cases (P=0.05) and under-transmitted to controls (P=0.02), showing association in FBAT analysis (P=0.03 dominant, P=0.01 additive). These results suggest folate pathway disruption contributes to AVSD risk in Down syndrome individuals.