rs3842

This pilot study investigated associations between genetic polymorphisms in transporter genes (SLC19A1, ABCC2, ABCB1, ABCC1, ABCC3, ABCG2) and clinical response to methotrexate (MTX) in 100 Chinese rheumatoid arthritis (RA) patients. Multiple SNPs showed significant associations with MTX response: SLC19A1 rs12659 and rs3788200 major alleles were associated with EULAR good/moderate response (RR=1.42-1.45, p=0.03-0.04); ABCC2 rs3740066 major allele was associated with DAS28-ESR low disease activity (RR=0.67, p=0.02). Haplotype analysis identified significant associations of SLC19A1 and ABCC2 haplotypes with clinical response outcomes.

This retrospective cohort study of 187 Brazilian HIV patients examined associations between seven SNPs in five pharmacokinetic genes and virological failure on first-line protease inhibitor-based antiretroviral therapy. Two variants were significantly associated with treatment failure: rs1045642 (ABCB1) and rs212091 (ABCC1), suggesting that genetic variation in drug transporter proteins influences treatment outcomes in this population.

This case-control study of 500 lung cancer patients and 517 controls in a Chinese population investigated associations between common variants in ABCB1 and ABCC1 transporter genes and lung cancer risk. The ABCB1 rs3842 variant genotype (A/G + G/G) was associated with significantly increased lung cancer risk (OR 1.36, 95% CI 1.06-1.76), as was the ABCC1 rs212090 variant genotype (A/T + T/T) (OR 1.37, 95% CI 1.03-1.83). Stratification analysis showed particularly strong associations with rs3842 in women (OR 2.57), adenocarcinoma histologic type (OR 1.42), and individuals under age 60 (OR 1.50).

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).