Rs1057910

SNP rs1057910(A), located in the cytochrome p450 CYP2C9 gene, most commonly encodes the amino acid isoleucine at position 359, and the resulting allele is also known as CYP2C9*1. rs1057910(C) encodes a leucine at this same position, and the resulting allele is called CYP2C9*3. This SNP is also known as Ile359Leu or A1075C.

The effect of CYP2C9 variants on drug metabolism should not be predicted without also considering CYP2C9*2, defined as the common loss of function variant rs1799853(T) (NM_000771:c.430C>T, NP_000762:p.144R>C).

Studies of the effects of these alleles include:


 * rs1057910(C;C) genotypes may clear drugs like celecoxib (trade name Celebrex) twice as slowly as rs1057910(A;A) genotypes; the rs1057910(A;C) genotypes are in-between clearance rates. Lower clearance rates will lead to higher internal concentrations of the drug. It is not clear whether this could lead to increased efficacy and/or increased side effects.


 * rs1057910(C;C) genotypes are poor metabolizers of tolbutamide, a sulfonylurea hypoglycemic drug used in the treatment of diabetes.


 * rs1057910(C;C) genotypes are poor metabolizers of phenytoin, a drug used to treat epilepsy, and therefore tend to need lower doses.


 * rs1057910(C;C) genotypes are poor metabolizers of glipizide, a second generation sulfonylurea drug structurally similar to tolbutamide and also used as an oral hypoglycemic agent.


 * rs1057910(C;C) genotypes are poor metabolizers of warfarin, and therefore unusually sensitive.


 * See also OMIM 601130.0001

Individuals carrying this SNP may show increased risk of developing acute gastrointestinal bleeding during the use of NSAIDs that are CYP2C8 or CYP2C9 substrates, such as aceclofenac, celecoxib, diclofenac, ibuprofen, indomethazine, lornoxicam, meloxicam, naproxen, piroxicam, tenoxicam and valdecoxib.

12x risk of severe cutaneous adverse reactions when taking antiepileptic drug phenytoin.