rs11045818 (SLCO1B1): toxic liver disease risk with statins

Key takeaways

• This variant affects how the body processes methotrexate, a drug used for acute lymphoblastic leukemia.
• It is linked to higher levels of a brain metabolite called 21-hydroxypregnenolone disulfate.
• The same variant also influences MEGF9 protein levels and circulating CTSC.

What the research says This variant is associated with methotrexate pharmacokinetics in acute lymphoblastic leukemia [PMID 19901119]. It also correlates with higher levels of the metabolite 21-hydroxypregnenolone disulfate [PMID 37253714].

Reported associations

• Methotrexate pharmacokinetics (acute lymphoblastic leukemia) - risk allele G leads to altered drug processing [PMID 19901119].
• Metabolite levels (21-hydroxypregnenolone disulfate) - risk allele A associated with higher metabolite levels [PMID 37253714].
• MEGF9 protein levels - risk allele A linked to increased protein levels [PMID 39789286].
• Circulating CTSC levels - risk allele A associated with altered circulating CTSC levels [PMID 42097137].

Evidence quality The variants are reported in GWAS Catalog entries with effect sizes ranging from 0.051 to 0.18, p-values below 1e-7, sample sizes up to ~58k individuals [PMIDs 42097137, 37253714, 39789286]. No conflicting findings reported.

Drug response and pharmacogenomics

• SLCO1B1 variants AA or AG increase likelihood of toxic liver disease when taking atorvastatin, fluvastatin, lovastatin, pitavastatin, simvastatin compared to GG genotype [PMID 38809397].

Tissue-specific expression effects

• SLCO1B1: increased expression in nerve_tibial [GTEx Portal].
• SLCO1B7: increased expression in nerve_tibial [GTEx Portal].
• ELOCP31: increased expression in skin_not_sun_exposed_suprapubic [GTEx Portal].

Lifestyle considerations No lifestyle considerations on file for this variant.