Rs4149056

From SNPedia

rs4149056, also known as 37041T>C or V174A, is a SNP in the SLCO1B1 gene, which encodes the 'organic anion transporting polypeptide 1B1' (OATP1B1) protein. This protein, found primarily in the liver, regulates the uptake of numerous drugs and natural compounds. The rs4149056(C) SNP defines the SLCO1B1*5 allele.

The rs4149056(C) allele gives rise to an amino acid change (from valine to alanine at residue 174) which has reduced uptake/transport activity. Therefore, drugs metabolized by OATP1B1 tend to build up to higher circulating concentrations than they would otherwise.[PMID 16758257].

The drugs known (or in some cases, thought) to be transported less well by the variant OATP1B1 protein encoded by the rs4149056(C) allele include:

• Several cholesterol lowering statins, generally leading to reduced inhibitory effects on liver cholesterol synthesis and possibly worse side effects, by such drugs as:
  • simvastatin
  • pravastatin
  • rosuvastatin
  • pitavastatin
• fexofenadine
• repaglinide
• methotrexate
• the SN-38 active metabolite of irinotecan
• rifampicin
• caspofungin
• lopinavir

[PMID 18650507] rs4363657 in nearly complete linkage disequilibrium with rs4149056 SNP (r²=0.97), which has been linked to statin metabolism. rs4149056(C) odds ratio for myopathy among 20,000 individuals taking either 40 or 80mg of simvastatin daily was 4.5 (CI: 2.6-7.7) per copy of the C allele, and 16.9 (CI: 4.7-61.1) in (C;C) as compared with (T;T) homozygotes.

The Gene Sherpa points out a 16x odds ratio for myopathy when taking statins and suggests fenofibrates might be a good alterative.

[PMID 19833260] A study of ~500 individuals taking statins concluded that rs4149056(C), i.e. SLCO1B1*5, was associated with statin-induced side-effects, most likely somewhat correlated to the number of such alleles being carried.

spittoon discussion of this SNP

[PMID 19414484] Genome-wide association meta-analysis for total serum bilirubin levels

[PMID 19642078] Prevalence of risk factors for statin-induced myopathy in rheumatoid arthritis patients

[PMID 19901119] Germline Genetic Variation in an Organic Anion Transporter Polypeptide Associated With Methotrexate Pharmacokinetics and Clinical Effects