rs11045879

A genome-wide association study (GWAS) of serum metabolic quantitative trait loci (mQTLs) in 891 Swedish men identified seven replicating loci (PYROXD2, FADS1, PON1, CYP4F2, UGT1A8, ACADL, and LIPC) with variants showing significant associations with metabolite levels (P = 10^-13 to 10^-91). rs4345897:A>G in PYROXD2 showed the strongest association with caprolactam (P = 2.40 × 10^-91), while rs174549:A>G in FADS1 associated with glycerolphosphocholine (P = 1.91 × 10^-30). Pathway analysis implicated genes with acyl-CoA dehydrogenase activity (ACADS, ACADM, ACAD8, ACAD10, ACAD11, ACOXL) and mQTL SNPs were enriched across GWAS catalog regions.

Case-control study of 1,000 Han Chinese individuals (450 epilepsy cases, 550 controls) examining associations between STX1B polymorphisms and epilepsy treatment response. The rs140820592 variant showed significant association with reduced epilepsy risk (OR=0.542, p=0.004) and drug-resistant epilepsy risk (OR=0.260, p=0.004), with eQTL analysis confirming rs140820592 regulates STX1B expression in brain tissues.

This retrospective candidate gene study analyzed 115 Spanish pediatric B-ALL patients treated with high-dose methotrexate (MTX) under the standardized LAL/SHOP protocol. The study examined 10 polymorphisms in 7 genes (MTHFR, TS, SHMT1, RFC1, ABCB1, ABCG2, SLCO1B1) involved in MTX metabolism and their association with MTX toxicity using plasma MTX concentration as an objective marker. The key finding was a statistically significant association between the SLCO1B1 rs11045879 CC genotype and high MTX plasma concentrations (p=0.030 univariate, p=0.008 multivariate), with all patients carrying the CC genotype showing elevated MTX levels. The rs4149081 AA genotype in SLCO1B1 was also associated with high MTX plasma concentrations (p=0.097 univariate, p=0.057 multivariate). No significant associations were found with the other 8 polymorphisms in MTHFR, TS, SHMT1, RFC1, ABCB1, or ABCG2 genes.