rs1650697

A case-control study of 540 cases and 400 controls in Bangladesh examined 25 candidate SNPs in inflammation, one-carbon metabolism, and skin cancer genes for associations with arsenic-induced skin lesions. Six SNPs showed significant gene-environment interactions with water arsenic exposure (PEMT rs2278952 P=0.004, rs897453 P=0.05; DHFR rs1650697 P=0.02; IL10 rs3024496 P=0.04; INPP5A rs1133400 P=0.03; XPC rs2228000 P=0.01), and the INPP5A rs1133400 interaction was successfully replicated in an independent population of 488 cases and 2,794 controls (P=0.03).

This case-control study examined 29 polymorphisms in four folate-mediated one-carbon metabolism pathway genes (MTHFD1, SHMT1, MTHFR, DHFR) in Hispanic and non-Hispanic white populations to assess their association with conotruncal heart defects. MTHFD1 rs11627387 was associated with a 1.7-fold increased risk in both Hispanic mothers (OR=1.7, 95% CI=1.1-2.5) and Hispanic infants (OR=1.7, 95% CI=1.2-2.3). MTHFR rs1801133 (C677T) showed a 2.8-fold increased risk among Hispanic mothers with low dietary folate intake, while rs1801131 (A1298C) showed a 2.0-fold increased risk among those with higher folate intake. Gene-folate interactions were observed, suggesting maternal multivitamin use and dietary folate intake may modify conotruncal heart defect risk.

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 pharmacogenetic study examined genetic variants in the folate metabolism and MTX transport pathways in rheumatoid arthritis patients receiving methotrexate monotherapy. Study 1 (n=124) identified rs17421511 and rs1476413 in MTHFR and rs1643650 in DHFR as significantly associated with MTX treatment response (p=0.024, p=0.0086, p=0.026 respectively), and rs16853826 and rs10197559 in ATIC as associated with toxicity (p=0.039). Study 2 (n=194) found rs10106 and rs10987742 in FPGS associated with response, and rs868755, rs10280623, rs1858923 in ABCB1 associated with toxicity, with rs10106 also associated with longer MTX monotherapy survival.

This pharmacogenetics study analyzed 28 SNPs in methotrexate (MTX) metabolism genes (SLC19A1/RFC1, ABCB1, FPGS, GGH) in two Spanish populations with rheumatoid arthritis (n=124 and n=194). Key findings: FPGS rs10987742 and rs10106 associated with MTX response (p=0.033, p=0.041); FPGS rs10106 also associated with MTX survival (p=0.005) and toxicity (p=0.021); ABCB1 rs868755, rs10280623, rs1858923 associated with toxicity (p=0.025, p=0.048, p=0.031). In the first study, MTHFR rs17421511 (p=0.024) and rs1476413 (p=0.0086) associated with response, DHFR rs1643650 (p=0.026) associated with response, ATIC rs16853826 associated with toxicity (p=0.039).