rs2274976

A case-control study of 152 NTD patients and 169 controls in Han Chinese population identified three folate metabolism pathway SNPs associated with neural tube defects: rs2236225 in MTHFD1 (allele A, OR=1.500; AA genotype OR=2.862), rs1801133 in MTHFR (allele T, OR=1.552; TT genotype OR=2.344), and rs1801394 in MTRR (allele G, OR=1.533; GG genotype OR=2.355). The study demonstrates genetic variation in folate metabolism significantly affects NTD susceptibility.

Case-control study of 501 young stroke patients and 1,211 controls examining 58 polymorphisms in 17 genes involved in methionine metabolism. Multiple logistic regression identified four independent risk factors for early-onset ischaemic stroke: rs10037045 BHMT (OR 1.38, p=0.033), rs682985 BHMT2 (OR 1.46, p=0.017), rs1051319 CBS (OR 3.75, p<0.0001), and rs202680 FOLH1 (OR 3.00, p<0.0001). Haplotype analyses identified significant associations with BHMT, CBS, FOLH1, MTR, PON2, TCN2 and TYMS haplotypes and stroke risk.

A hospital-based case-control study in rural and urban India (1,204 cases; 1,212 controls) examined genetic and lifestyle risk factors for breast cancer. Four SNPs in FGFR2 (rs1219648, rs2420946, rs2981575, rs2981582) showed positive associations with breast cancer (ORs 1.32-1.47). Additional SNPs in obesity and metabolic genes (rs374748 in FBN2, rs2922763 in HNF4G, rs2116830 in KCNMA1, rs11121832 in MTHFR, rs16886165 in MAP3K1, rs11594610 in TCF7L2, rs2274459 in MLN) were associated with increased breast cancer risk. Waist-to-hip ratio ≥0.95 showed strong association (OR 3.78; 95% CI 2.92-4.89), and women living first 20 years in rural areas showed protective effect (OR 0.77).

This deep sequencing study of the MTHFR gene identified variants associated with myelomeningocele (a neural tube defect) in 96 affected subjects (49 Caucasian, 47 Mexican American). The authors discovered one novel intronic splice site variant (c.171+3G>T) and found seven SNPs with significant allele frequency differences compared to ethnically matched reference populations (p ≤ 0.05, Fisher's exact test), including five SNPs (rs13306561, rs2274976, rs2066462, rs12121543, rs1476413) not previously associated with neural tube defects.

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.