rs4149056

rs4149056, also known as c.521T>C, Val174Ala 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.. 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 rs4363657 in nearly complete linkage disequilibrium with rs4149056 SNP (r 2 =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. From Coriell (re SLCO1B1 haplotypes): *rs72559745 (SLCO1B1*1) AA AA *rs56061388 (SLCO1B1*3) TT TT *rs4149056 (SLCO1B1*5) TT TT *rs55901008 (SLCO1B1*6) TT TT 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. A study of >4000 individuals with type 2 diabetes using routine prescribing data from the Electronic Medical Record in Tayside Scotland suggests high proportion rs4149056(C) homozygotes discontinue or reduce their doses of statins 23andMe blog discussion of this SNP SLCO1B1 genetic variant associated with statin-induced myopathy: a proof-of-concept study using the clinical practice research datalink Statin Response

C;C

reduced breakdown of some drugs; CPIC Recommendation: Prescribe a lower dose (20mg daily) or consider an alternative statin (e.g., pravastatin or rosuvastatin); consider routine creatine kinase (CK) surveillance. significantly associated with myopathy in patients who received simvastatin, but not in patients who received atorvastatin. PMID 21243006 however it did not affect pravastatin.