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rs2231142

From SNPedia

gout
Orientationminus
Stabilizedminus
Geno Mag Summary
(A;A) 3.5 causes gout
(A;C) 2.1 1.74x increased gout risk; gefinitib takers 4x more susceptible to diarrhea
(C;C) 0 normal
ReferenceGRCh38.p2 38.2/146
Chromosome4
Position88131171
GeneABCG2
is asnp
is mentioned by
dbSNPrs2231142
ebirs2231142
HLIrs2231142
Exacrs2231142
Varsomers2231142
Maprs2231142
PheGenIrs2231142
hapmaprs2231142
1000 genomesrs2231142
hgdprs2231142
ensemblrs2231142
gopubmedrs2231142
geneviewrs2231142
scholarrs2231142
googlers2231142
pharmgkbrs2231142
gwascentralrs2231142
openSNPrs2231142
23andMers2231142
23andMe allrs2231142
SNP Nexus

SNPshotrs2231142
SNPdbers2231142
MSV3drs2231142
GWAS Ctlgrs2231142
GMAF0.1391
Max Magnitude3.5
? (A;A) (A;C) (C;C) 28
rs2231142, also known as Q141K and C421A, is a SNP in the ABCG2 gene, indicating a missense variant.

[PMID 19506252OA-icon.png] "Our data indicate that at least 10% of all gout cases in whites are attributable to this causal variant."

A is the risk allele. A large study totaling 7,699 participants in the Framingham cohort and 4,148 participants in the Rotterdam cohort was conducted, with genome-wide significant SNPs then replicated in 11,000+ Caucasian and ~4,000 African-American individuals who took part in the study of Atherosclerosis Risk in Communities (ARIC). This study calculated an odds ratio of 1.74 for rs2231142 (CI: 1.51-1.99, p = 3.3x10e-15). A genetic score comprised of this SNP plus 2 others may stratify risk for gout. [PMID 18834626OA-icon.png]

Among non-small cell lung cancer patients treated with gefitinib, there's a 4-5x higher risk of diarrhea for rs2231142 heterozygotes (and presumably minor allele homozygotes), based on a study of 124 patients treated with 250mg oral gefitinib once daily.[PMID 17148776]

rs2231142 also appears to influence the effectiveness of rosuvastatin. A study of 305 Chinese patients concluded that rs2231142(A;A) individuals showed a 7% greater reduction in LDL-C levels, equivalent to a doubling of the dose.[PMID 20130569]

See also: 23andMe blog gout


[PMID 19503597OA-icon.png] Meta-Analysis of 28,141 Individuals Identifies Common Variants within Five New Loci That Influence Uric Acid Concentrations

OMIM612670
DescURIC ACID CONCENTRATION, SERUM, QUANTITATIVE TRAIT LOCUS 3; UAQTL3
Variant
Relatedalso
[PMID 19890391OA-icon.png] Common polymorphisms influencing serum uric Acid levels contribute to susceptibility to gout, but not to coronary artery disease



[PMID 20421215] The rs2231142 variant of the ABCG2 gene is associated with uric acid levels and gout among Japanese people











[PMID 21918980OA-icon.png] A comprehensive study of polymorphisms in the ABCB1, ABCC2, ABCG2, NR1I2 genes and lymphoma risk


[PMID 22015057] Single nucleotide polymorphism associations with response and toxic effects in patients with advanced renal-cell carcinoma treated with first-line sunitinib: a multicentre, observational, prospective study

GWAS snp
PMID [PMID 22229870OA-icon.png]
Trait
Title Genome-wide association of serum uric Acid concentration: replication of sequence variants in an island population of the Adriatic coast of croatia.
Risk Allele T
P-val 0.000005
Odds Ratio 27.4000 None


[PMID 18547414OA-icon.png] Genotyping panel for assessing response to cancer chemotherapy.


[PMID 19474294OA-icon.png] Potential etiologic and functional implications of genome-wide association loci for human diseases and traits.


[PMID 19842935] Different effects of the ABCG2 c.421C>A SNP on the pharmacokinetics of fluvastatin, pravastatin and simvastatin.


[PMID 19930591OA-icon.png] Polymorphisms in the xenobiotic transporter Multidrug Resistance 1 (MDR1) and interaction with meat intake in relation to risk of colorectal cancer in a Danish prospective case-cohort study.


[PMID 20053405OA-icon.png] Sex and age interaction with genetic association of atherogenic uric acid concentrations.


[PMID 20162742OA-icon.png] Predictive value of 8 genetic loci for serum uric acid concentration.


[PMID 20162743OA-icon.png] Common variants in SLC17A3 gene affect intra-personal variation in serum uric acid levels in longitudinal time series.


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


[PMID 20470424OA-icon.png] A three-stage approach for genome-wide association studies with family data for quantitative traits.


[PMID 20714133] Association of four genetic loci with uric acid levels and reduced renal function: the J-SHIPP Suita study.


[PMID 20837191] Gout: epitome of painful arthritis.


[PMID 20858603] A strong role for the ABCG2 gene in susceptibility to gout in New Zealand Pacific Island and Caucasian, but not Maori, case and control sample sets.


[PMID 20959405] The IFNG (IFN-gamma) genotype predicts cytogenetic and molecular response to imatinib therapy in chronic myeloid leukemia.


[PMID 22112610OA-icon.png] Common variants in ABCB1, ABCC2 and ABCG2 genes and clinical outcomes among women with advanced stage ovarian cancer treated with platinum and taxane-based chemotherapy: a Gynecologic Oncology Group study.


GET Evidence
ABCG2-Q141K
aa_change Gln141Lys
aa_change_short Q141K
impact pharmacogenetic
qualified_impact Insufficiently evaluated pharmacogenetic
overall_frequency 0.0819855
summary Significantly altered kintetics and increase plasma AUC with diflomotecan and rosuvastatin.



[PMID 23280364] Interindividual variability in the hepatic expression of the human breast cancer resistance protein (BCRP/ABCG2): Effect of age, sex, and genotype

GWAS snp
PMID [PMID 23263486OA-icon.png]
Trait Urate levels
Title Genome-wide association analyses identify 18 new loci associated with serum urate concentrations.
Risk Allele T
P-val 1E-134
Odds Ratio .22 [0.20-0.23] mg/dl increase


[PMID 23827224] Association between the ABCG2 C421A polymorphism and Alzheimer's disease


[PMID 23864233] Association between serum uric acid and the metabolic syndrome among a middle- and old-age Chinese population


[PMID 24380367OA-icon.png] Epigenetic modulation of the drug resistance genes MGMT, ABCB1 and ABCG2 in glioblastoma multiforme


[PMID 24499401] The ABCG2 gene Q141K polymorphism contributes to an increased risk of gout: A meta-analysis of 2185 cases


[PMID 23100282OA-icon.png] Impact of common genetic variation on response to simvastatin therapy among 18 705 participants in the Heart Protection Study.


[PMID 23438071] The JR blood group system: identification of alleles that alter expression.


[PMID 23712608] Genetic variability related to serum uric acid concentration and risk of Parkinson's disease.


[PMID 23778707] International Transporter Consortium commentary on clinically important transporter polymorphisms.


[PMID 24777469] The association between the polymorphism rs2231142 in the ABCG2 gene and gout risk: a meta-analysis


[PMID 24513273OA-icon.png] A genome-wide association study identifies common variants influencing serum uric acid concentrations in a Chinese population

GWAS snp
PMID [PMID 21983786]
Trait Gout
Title Identification of low-frequency variants associated with gout and serum uric acid levels.
Risk Allele T
P-val 3E-12
Odds Ratio 1.67 [1.43-1.92]


ClinVar
Risk rs2231142(A;A)
Alt rs2231142(A;A)
Reference rs2231142(C;C)
Significance Other
Disease Uric acid concentration Blood group rosuvastatin response - Efficacy
Variation info
Gene ABCG2
CLNDBN Uric acid concentration, serum, quantitative trait locus 1 Blood group, Junior system rosuvastatin response - Efficacy
Reversed 1
HGVS NC_000004.11:g.89052323G>T
CLNSRC OMIM Allelic Variant PharmGKB Clinical Annotation PharmGKB
CLNACC RCV000023341.2, RCV000023342.2, RCV000211355.1,



[PMID 25867401] Polymorphisms of uric transporter proteins in the pathogenesis of gout in a Chinese Han population


[PMID 25128519] Tubular urate transporter gene polymorphisms differentiate patients with gout who have normal and decreased urinary uric acid excretion


[PMID 25676789] Genome-wide association study identifies ABCG2 (BCRP) as an allopurinol transporter and a determinant of drug response


[PMID 26552468] Genetic analysis of ABCG2 and SLC2A9 gene polymorphisms in gouty arthritis in a Korean population


[PMID 26810134] ABCG2 loss-of-function polymorphism predicts poor response to allopurinol in patients with gout.


[PMID 27511497] Association analysis of five SNP variants with gout in the Minnan population in China.