What does the SLCO1B1 gene do?

SLCO1B1 encodes OATP1B1, a transporter protein in the liver that moves hormones and certain drugs from the bloodstream into liver cells for metabolism and removal. Variants in this gene can alter how efficiently this transport works.

Is rs10841753 linked to methotrexate side effects?

The studies reviewed here identified other specific SLCO1B1 variants as the primary genetic signals for methotrexate pharmacokinetics and GI toxicity. Whether rs10841753 specifically carries the same associations has not been established in the reviewed data.

What is an eQTL and why does it matter for rs10841753?

An eQTL (expression quantitative trait locus) is a variant associated with differences in how much a nearby gene is expressed in a tissue. GTEx data show rs10841753 is linked to increased SLCO1B1 expression in tibial nerve tissue and reduced RECQL expression in liver tissue, though these tissue-level effects have not been directly connected to clinical outcomes in the reviewed studies.

Is rs10841753 linked to breast cancer risk?

The studies reviewed here did not assess breast cancer risk for rs10841753 directly. SLCO1B1 variants were studied in women already diagnosed with ER+ breast cancer, where they influenced estrogen metabolism rather than cancer occurrence itself.

What is the RECQL gene?

RECQL encodes a DNA helicase, an enzyme involved in unwinding and repairing DNA strands. The reviewed studies do not discuss RECQL directly; the link to rs10841753 comes solely from GTEx expression data showing reduced RECQL levels in liver tissue.

rs10841753 (SLCO1B1): Estrogen and Drug Transport

Key takeaways

rs10841753 sits within SLCO1B1, a gene encoding a liver transporter (OATP1B1) that moves estrogens and certain cancer drugs from the bloodstream into liver cells for processing.
SLCO1B1 variants are the strongest known genetic factor shaping methotrexate blood levels in children receiving treatment for leukemia.
Certain SLCO1B1 variants are linked to 15- to 16-fold higher odds of gastrointestinal side effects from high-dose methotrexate.
SLCO1B1 variation also influences circulating estrone conjugate levels in postmenopausal women with ER+ breast cancer, with genome-wide significant associations found by GWAS.
GTEx data show rs10841753 is linked to higher SLCO1B1 expression in tibial nerve tissue and lower RECQL expression in liver tissue.

What the research says

rs10841753 sits within SLCO1B1 (encoding OATP1B1, a hepatic influx transporter that ferries hormones and certain drugs from blood into liver cells), a gene whose variants shape both hormone metabolism and drug pharmacokinetics. A GWAS (genome-wide association study) in 774 postmenopausal women with resected early-stage ER+ breast cancer identified multiple SLCO1B1 SNPs (single-nucleotide polymorphisms) as genome-wide significant determinants of plasma estrone conjugate (E1C) concentrations and the E1C/estrone ratio, with the top SNP reaching p = 3.74e-11. A separate GWAS across 434 children with acute lymphoblastic leukemia (ALL) receiving 3,014 courses of high-dose methotrexate identified this locus as the dominant genetic influence on methotrexate plasma disposition, with top signals validated in an independent cohort of 206 patients PMID 19597016.

Reported associations

Plasma estrone conjugate (E1C) concentrations: Multiple SLCO1B1 SNPs reached genome-wide significance (top SNP p = 3.74e-11) for E1C plasma levels in 774 postmenopausal women with ER+ breast cancer; patients homozygous for the variant allele of the missense SNP rs4149056 had significantly higher average E1C concentrations than other patients.
E1C/estrone ratio: SNPs across this locus that are not in linkage disequilibrium (LD, meaning not co-inherited) with the missense variant rs4149056 were independently associated with the E1C/estrone ratio, pointing to more than one distinct functional mechanism within this gene.
Methotrexate plasma exposure: Two SLCO1B1 SNPs, rs11045879 (p = 1.7e-10) and rs4149081 (p = 1.7e-9), in high LD with each other and with rs4149056, were the top genome-wide signals for methotrexate plasma concentration across 3,014 treatment courses in 434 children with ALL, replicated independently in 206 patients PMID 19597016.
Gastrointestinal toxicity from methotrexate: SLCO1B1 SNPs were associated with GI toxicity from high-dose methotrexate at odds ratios of 15.3 to 16.4 (p = 0.03 to 0.004) in the same pediatric ALL cohort PMID 19597016.

Evidence quality

The methotrexate pharmacokinetics findings are among the better-replicated results in cancer pharmacogenomics: the primary analysis covered 3,014 treatment courses in 434 pediatric ALL patients and confirmed the top SLCO1B1 signals in an independent cohort of 206 additional patients (replication p = 0.017-0.018) PMID 19597016. The estrogen GWAS included 774 postmenopausal women and reached genome-wide significance at this locus (p = 3.74e-11), though external replication of the E1C-specific findings was not reported in the provided study text. Neither study explicitly names rs10841753 as a variant under investigation; the associations above are for other SLCO1B1 variants within the same gene, and whether rs10841753 is in LD with any of these index SNPs is not established by the reviewed data. The GTEx expression data are drawn from 953 donors across tissues at FDR < 0.05, and the eQTL effects reported here are tissue-expression associations only, not clinical outcome predictions.

Tissue-specific expression effects

SLCO1B1: The ALT allele of rs10841753 is associated with increased SLCO1B1 expression in tibial nerve tissue GTEx Portal.
RECQL: The same allele is associated with reduced RECQL expression in liver tissue GTEx Portal.

Lifestyle considerations

No lifestyle considerations on file for this variant.

rs10841753 (SLCO1B1): Estrogen and Drug Transport

Key takeaways

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