rs10509681

plus

Geno	Mag	Summary
(C;C)	2	>1.81x risk of GI bleeding with some NSAID drugs
(C;T)	1.5	Increased risk of GI bleeding with NSAIDs
(T;T)	1	No increased risk of GI bleeding on NSAID drugs

Reference

GRCh38 38.1/142

Chromosome

10

Position

95038992

Gene

CYP2C8

is a	snp
is	mentioned by
dbSNP	rs10509681
dbSNP (classic)	rs10509681
ClinGen	rs10509681
ebi	rs10509681
HLI	rs10509681
Exac	rs10509681
Gnomad	rs10509681
Varsome	rs10509681
LitVar	rs10509681
Map	rs10509681
PheGenI	rs10509681
Biobank	rs10509681
1000 genomes	rs10509681
hgdp	rs10509681
ensembl	rs10509681
geneview	rs10509681
scholar	rs10509681
google	rs10509681
pharmgkb	rs10509681
gwascentral	rs10509681
openSNP	rs10509681
23andMe	rs10509681
SNPshot	rs10509681
SNPdbe	rs10509681
MSV3d	rs10509681
GWAS Ctlg	rs10509681

GMAF

0.06474

Max Magnitude

2

?

(C;C) (C;T) (T;T)

28

This is a CYP2C8 SNP. The CYP2C8*3 allele is mapped to both rs10509681 and rs11572080).

[PMID 19422321] In a 2009 article titled "Genetically based impairment in CYP2C8- and CYP2C9-dependent NSAID metabolism as a risk factor for gastrointestinal bleeding: is a combination of pharmacogenomics and metabolomics required to improve personalized medicine?" It is claimed that individuals carrying minor alleles of this SNP (usually heterozygotes, since minor homozygotes are rare) 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.

[PMID 18216720] In a 2008 article (reviewed in [PMID 19422321]) titled "Interaction of CYP2C8 and CYP2C9 genotypes modifies the risk for nonsteroidal anti-inflammatory drugs-related acute gastrointestinal bleeding," the study discovered that carriers of CYP2C8*3 (a minor allele of both rs10509681 and rs11572080) had a GI bleeding event risk OR=1.81 (95% CI=0.95–3.46; P=0.071) and risk increased if carriers drank more than 20g alcohol/day to an OR=1.99 (95% CI=1.06–3.74; P=0.034). As CYP2C8*3 and CYP2C9*2 rs1799853 variant alleles are in linkage disequilibrium, patients are likely to carry the risk allele to both 8*3 and 9*2, and when they do, The OR (95% CI) for carriers of such a genotype is increased to 1.94 (1.13–3.33), P=0.017.

[PMID 18216720 ] A 2013 NIH review titled "PharmGKB summary: very important pharmacogene information for cytochrome P450, family 2, subfamily C, polypeptide 8" reiterated that "some data suggest that the combined presence of minor risk alleles CYP2C8*3 (rs10509681 and rs11572080) and CYP2C9*2 rs1799853 is a determinant of NSAID-induced gastrointestinal bleeding." They cited [PMID 18216720].

[PMID 18769365 ] Role of cytochrome P450 2C8 and 2J2 genotypes in calcineurin inhibitor-induced chronic kidney disease.

[PMID 19761371 ] Cytochrome P450 2C8 pharmacogenetics: a review of clinical studies.

[PMID 20389299 ] Pazopanib-induced hyperbilirubinemia is associated with Gilbert's syndrome UGT1A1 polymorphism.

[PMID 20808793 ] Are cytochrome P450 CYP2C8 and CYP2C9 polymorphisms associated with ibuprofen response in very preterm infants?

[PMID 21324488] Single nucleotide polymorphisms in tobacco metabolism and DNA repair genes and prognosis in resected non-small-cell lung cancer.

[PMID 23267857] CYP2C19*17 Gain-of-Function Polymorphism Is Associated With Peptic Ulcer Disease

[PMID 23413280 ] CYP2C8*3 increases risk of neuropathy in breast cancer patients treated with paclitaxel

[PMID 23420707 ] Analysis of the Functional Polymorphism in the Cytochrome P450 CYP2C8 Gene rs11572080 with Regard to Colorectal Cancer Risk

[PMID 23130019 ] Frequencies of 23 functionally significant variant alleles related with metabolism of antineoplastic drugs in the chilean population: comparison with caucasian and asian populations.

[PMID 23426382] The role of genetic variants in CYP2C8, LPIN1, PPARGC1A and PPARgamma on the trough steady-state plasma concentrations of rosiglitazone and on glycosylated haemoglobin A1c in type 2 diabetes.

ClinVar
Risk	Rs10509681(C;C)
Alt	Rs10509681(C;C)
Reference	Rs10509681(T;T)
Significance	Drug-response
Disease	rosiglitazone response - Dosage
Variation	info
Gene	CYP2C8
CLNDBN	rosiglitazone response - Dosage
Reversed	0
HGVS	NC_000010.10:g.96798749T>C
CLNSRC
CLNACC	RCV000417126.1,