{{Rsnum
|rsid=2231142
|Gene=ABCG2
|Chromosome=4
|position=88131171
|Orientation=minus
|ReferenceAllele=C
|MissenseAllele=A
|GMAF=0.1391
|Assembly=GRCh38
|GenomeBuild=38.1
|dbSNPBuild=141
|Summary=causes gout
|geno1=(A;A)
|geno2=(A;C)
|geno3=(C;C)
|Gene_s=ABCG2
}}{{ population diversity
| geno1=(A;A)
| geno2=(A;C)
| geno3=(C;C)
| CEU | 0.9 | 20.4 | 78.8
| HCB | 8.8 | 40.9 | 50.4
| JPT | 9.7 | 48.7 | 41.6
| YRI | 0.0 | 2.1 | 97.9
| ASW | 0.0 | 8.8 | 91.2
| CHB | 8.8 | 40.9 | 50.4
| CHD | 8.3 | 47.7 | 44.0
| GIH | 0.0 | 14.9 | 85.1
| LWK | 0.0 | 0.0 | 0.0
| MEX | 5.2 | 34.5 | 60.3
| MKK | 0.0 | 1.9 | 98.1
| TSI | 1.0 | 12.9 | 86.1
| HapMapRevision=28
}}[[rs2231142]], also known as Q141K and C421A, is a SNP in the [[ABCG2]] gene, indicating a missense variant.

{{PMID|19506252|OA=1
}}  "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|18834626|OA=1
}}

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: [http://blog.23andme.com/2008/10/01/snpwatch-three-new-associations-for-gout-strengthen-genetic-link/ 23andMe blog] [[gout]]

{{PMID Auto
|PMID=19503597
|Title=Meta-Analysis of 28,141 Individuals Identifies Common Variants within Five New Loci That Influence Uric Acid Concentrations
|OA=1
}}

{{omim
|desc=URIC ACID CONCENTRATION, SERUM, QUANTITATIVE TRAIT LOCUS 3; UAQTL3
|id=612670
|rsnum=2231142
}}
{{PMID Auto
|PMID=19890391
|Title=Common polymorphisms influencing serum uric Acid levels contribute to susceptibility to gout, but not to coronary artery disease
|OA=1
}}

{{PharmGKB
|RSID=rs2231142
|Name_s=ABCG2:421C>A; ABCG2:Q141K;
|Gene_s=ABCG2
|Feature=Exon/NonSyn
|Evidence=PubMed ID:16784736
|Annotation=study size=14, only SLCO1B1 521TT and CYP2C9*1/*1 wild-type homozygotes . ethnicity=Japanese. PK and signficance= AUC of rosuvastatin were lower in the 421CC group than in the 421CA+421AA group P=0.018; C(max) value was higher in the 421CA+421AA group than that in the 421CC group P=0.048; CL/F was lower in the 421CA+421AA group than that in the 421CC group P=0.043). The T(1/2) and T(max) values showed no difference between 421CC vs 421CA+421AA
|Drugs=rosuvastatin
|Drug Classes=
|Diseases=
|Curation Level=Curated
|PharmGKB Accession ID=PA165109681
}}

{{PMID Auto
|PMID=20421215
|Title=The rs2231142 variant of the ABCG2 gene is associated with uric acid levels and gout among Japanese people
}}

{{PharmGKB
|RSID=rs2231142
|Name_s=ABCG2:421C>A; ABCG2:Q141K; rs2231142
|Gene_s=ABCG2
|Feature=Exon/NonSyn
|Evidence=PubMed ID:17148776
|Annotation=Lung cancer patients carrying the A allele of ABCG2:421C>A were at increased risk for diarrhea but not skin toxicity following oral gefitinib treatment.
|Drugs=gefitinib
|Drug Classes=
|Diseases=Carcinoma, Non-Small-Cell Lung; Diarrhea; Lung Neoplasms
|Curation Level=Curated
|PharmGKB Accession ID=PA162355480
}}

{{PharmGKB
|RSID=rs2231142
|Name_s=ABCG2:421C>A; ABCG2:Q141K; rs2231142
|Gene_s=ABCG2
|Feature=Exon/NonSyn
|Evidence=PubMed ID:15229462
|Annotation=The ABCG2 421C>A genotype significantly affected the pharmacokinetics of diflomotecan in 5 patients heterozygous for this allele.
|Drugs=diflomotecan
|Drug Classes=
|Diseases=Neoplasms
|Curation Level=Curated
|PharmGKB Accession ID=PA162364098
}}

{{PharmGKB
|RSID=rs2231142
|Name_s=
|Gene_s=ABCG2
|Feature=Exon/NonSyn
|Evidence=PubMed ID:18834626; Web Resource:http://www.genome.gov/gwastudies/
|Annotation=GWAS results: Association of three genetic loci with uric acid concentration and risk of gout: a genome-wide association study. (Initial Sample Size: 11,847 individuals; Replication Sample Size: 14,867 individuals); (Region: 4q22.1; Reported Gene(s): ABCG2; Risk Allele: rs2231142-?); (p-value= 3E-60).This variant is associated with Serum urate.
|Drugs=
|Drug Classes=
|Diseases=
|Curation Level=Non-Curated
|PharmGKB Accession ID=PA164740843
}}

{{PharmGKB
|RSID=rs2231142
|Name_s=ABCG2:421C>A
|Gene_s=ABCG2
|Feature=Exon/NonSyn
|Evidence=PubMed ID:19474787
|Annotation=A allele is associated with increased rosuvastatin plasma AUC
|Drugs=rosuvastatin
|Drug Classes=
|Diseases=
|Curation Level=Curated
|PharmGKB Accession ID=PA164889046
}}

{{PharmGKB
|RSID=rs2231142
|Name_s=ABCG2: Q141K
|Gene_s=ABCG2
|Feature=Exon/NonSyn
|Evidence=PubMed ID:19506252
|Annotation=Introduction of the mutation Q141K in the ABCG2 gene by site-directed mutagenesis resulted in 53% reduced urate transport rates compared to wild-type ABCG2 (P < 0.001). Data of this study indicate that at least 10% of all gout cases in whites are attributable to this causal variant.
|Drugs=
|Drug Classes=
|Diseases=Gout
|Curation Level=Curated
|PharmGKB Accession ID=PA164918226
}}

{{PharmGKB
|RSID=rs2231142
|Name_s=
|Gene_s=ABCG2
|Feature=Exon/NonSyn
|Evidence=PubMed ID:18834626; Web Resource:http://www.genome.gov/gwastudies/
|Annotation=Association of three genetic loci with uric acid concentration and risk of gout: a genome-wide association study. (Initial Sample Size: 11,847 individuals; Replication Sample Size: 14,867 individuals); (Region: 4q22.1; Reported Gene: ABCG2; Risk Allele: rs2231142-?) This variant is associated with Serum urate.
|Drugs=
|Drug Classes=
|Diseases=
|Curation Level=Non-Curated
|PharmGKB Accession ID=PA164740885
}}

{{PharmGKB
|RSID=rs2231142
|Name_s=ABCG2:c.421C>A (Gln141Lys)
|Gene_s=ABCG2
|Feature=Exon/NonSyn
|Evidence=PubMed ID:20130569
|Annotation=Risk or phenotype-associated allele: A allele. Phenotype: Greater reduction in LDL-C level. Study size: 305. Study population/ethnicity: Chinese patients with hypercholesterolemia treated with rosuvastatin. Significance metric(s): overall P = 0.0006. Type of association: GN; PD
|Drugs=rosuvastatin
|Drug Classes=
|Diseases=Hypercholesterolemia
|Curation Level=Curated
|PharmGKB Accession ID=PA165291910
}}

{{PharmGKB
|RSID=rs2231142
|Name_s=ABCG2:421C>A; ABCG2:Q141K;
|Gene_s=ABCG2
|Feature=Exon/NonSyn
|Evidence=PubMed ID:18981009
|Annotation=studied allele=A; study size=46 (30 children; 16 adults);PK=significantly lower clearance (-23%) of imatinib and major metabolite in heterozygous versus wild-type homozygous patients when genotype considered with body weight, albuminemia and alpha1-acid glycoprotein covariates; significance= P < 0.05; genotype alone not associated with increased clearance
|Drugs=imatinib
|Drug Classes=
|Diseases=
|Curation Level=Curated
|PharmGKB Accession ID=PA165109629
}}

{{PharmGKB
|RSID=rs2231142
|Name_s=ABCG2:421C>A; ABCG2:Q141K;
|Gene_s=ABCG2
|Feature=Exon/NonSyn
|Evidence=PubMed ID:17509035
|Annotation=control size=7; K141 cases=6; PK=in healthy subjects, disposition of lamivudine was not significantly influenced by known functional variants
|Drugs=lamivudine
|Drug Classes=
|Diseases=
|Curation Level=Curated
|PharmGKB Accession ID=PA165109682
}}

{{PMID Auto
|PMID=21918980
|Title=A comprehensive study of polymorphisms in the ABCB1, ABCC2, ABCG2, NR1I2 genes and lymphoma risk
|OA=1
}}

{{PMID Auto
|PMID=22015057
|Title=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
}}

{{PMID Auto GWAS
|PMID=22229870
|Trait=None
|Title=Genome-wide association of serum uric Acid concentration: replication of sequence variants in an island population of the Adriatic coast of croatia.
|RiskAllele=T
|Pval=0.000005
|OR=27.4000
|ORtxt=None
|OA=1
}}

{{PMID Auto
|PMID=18547414
|Title=Genotyping panel for assessing response to cancer chemotherapy.
|OA=1
}}

{{PMID Auto
|PMID=19474294
|Title=Potential etiologic and functional implications of genome-wide association loci for human diseases and traits.
|OA=1
}}

{{PMID Auto
|PMID=19842935
|Title=Different effects of the ABCG2 c.421C>A SNP on the pharmacokinetics of fluvastatin, pravastatin and simvastatin.
}}

{{PMID Auto
|PMID=19930591
|Title=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.
|OA=1
}}

{{PMID Auto
|PMID=20053405
|Title=Sex and age interaction with genetic association of atherogenic uric acid concentrations.
|OA=1
}}

{{PMID Auto
|PMID=20162742
|Title=Predictive value of 8 genetic loci for serum uric acid concentration.
|OA=1
}}

{{PMID Auto
|PMID=20162743
|Title=Common variants in SLC17A3 gene affect intra-personal variation in serum uric acid levels in longitudinal time series.
|OA=1
}}

{{PMID Auto
|PMID=20389299
|Title=Pazopanib-induced hyperbilirubinemia is associated with Gilbert's syndrome UGT1A1 polymorphism.
|OA=1
}}

{{PMID Auto
|PMID=20470424
|Title=A three-stage approach for genome-wide association studies with family data for quantitative traits.
|OA=1
}}

{{PMID Auto
|PMID=20714133
|Title=Association of four genetic loci with uric acid levels and reduced renal function: the J-SHIPP Suita study.
}}

{{PMID Auto
|PMID=20837191
|Title=Gout: epitome of painful arthritis.
}}

{{PMID Auto
|PMID=20858603
|Title=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 Auto
|PMID=20959405
|Title=The IFNG (IFN-gamma) genotype predicts cytogenetic and molecular response to imatinib therapy in chronic myeloid leukemia.
}}

{{PMID Auto
|PMID=22112610
|Title=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.
|OA=1
}}

{{GET Evidence
|gene=ABCG2
|aa_change=Gln141Lys
|aa_change_short=Q141K
|impact=pharmacogenetic
|qualified_impact=Insufficiently evaluated pharmacogenetic
|inheritance=unknown
|quality_scores=Array
|dbsnp_id=rs2231142
|overall_frequency_n=882
|overall_frequency_d=10758
|overall_frequency=0.0819855
|n_genomes=10
|n_genomes_annotated=0
|n_haplomes=12
|n_articles=8
|n_articles_annotated=8
|in_gwas=Y
|in_pharmgkb=Y
|pph2_score=0.548
|nblosum100=-2
|autoscore=2
|webscore=N
|summary_short=Significantly altered kintetics and increase plasma AUC with diflomotecan and rosuvastatin.
}}

{{PMID Auto
|PMID=23280364
|Title=Interindividual variability in the hepatic expression of the human breast cancer resistance protein (BCRP/ABCG2): Effect of age, sex, and genotype
}}

{{PMID Auto GWAS
  |PMID=23263486
  |Trait=Urate levels
  |Title=Genome-wide association analyses identify 18 new loci associated with serum urate concentrations.
  |RiskAllele=T
  |Pval=1E-134
  |OR=.22
  |ORtxt=[0.20-0.23] mg/dl increase
  |OA=1
}}

{{PMID Auto
|PMID=23827224
|Title=Association between the ABCG2 C421A polymorphism and Alzheimer's disease
}}

{{PMID Auto
|PMID=23864233
|Title=Association between serum uric acid and the metabolic syndrome among a middle- and old-age Chinese population
}}

{{PMID Auto
|PMID=24380367
|Title=Epigenetic modulation of the drug resistance genes MGMT, ABCB1 and ABCG2 in glioblastoma multiforme
|OA=1
}}

{{PMID Auto
|PMID=24499401
|Title=The ABCG2 gene Q141K polymorphism contributes to an increased risk of gout: A meta-analysis of 2185 cases
}}

{{PMID Auto
|PMID=23100282
|Title=Impact of common genetic variation on response to simvastatin therapy among 18 705 participants in the Heart Protection Study.
|OA=1
}}

{{PMID Auto
|PMID=23438071
|Title=The JR blood group system: identification of alleles that alter expression.
}}

{{PMID Auto
|PMID=23712608
|Title=Genetic variability related to serum uric acid concentration and risk of Parkinson's disease.
}}

{{PMID Auto
|PMID=23778707
|Title=International Transporter Consortium commentary on clinically important transporter polymorphisms.
}}

{{PMID Auto
|PMID=24777469
|Title=The association between the polymorphism rs2231142 in the ABCG2 gene and gout risk: a meta-analysis
}}

{{PMID Auto
|PMID=24513273
|Title=A genome-wide association study identifies common variants influencing serum uric acid concentrations in a Chinese population
}}
{{on chip | 23andMe v1}}
{{on chip | 23andMe v2}}
{{on chip | 23andMe v3}}
{{on chip | 23andMe v4}}
{{on chip | Illumina Human 1M}}