Have questions? Visit https://www.reddit.com/r/SNPedia


From SNPedia

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
is asnp
is mentioned by
dbSNP (classic)rs2231142
1000 genomesrs2231142
GWAS Ctlgrs2231142
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


[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]
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.

[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]

Risk Rs2231142(A;A)
Alt Rs2231142(A;A)
Reference Rs2231142(C;C)
Significance Other
Disease Uric acid concentration Blood group rosuvastatin response - Efficacy allopurinol response - Efficacy Ovarian Neoplasms
Variation info
Gene ABCG2
CLNDBN Uric acid concentration, serum, quantitative trait locus 1 Blood group, Junior system rosuvastatin response - Efficacy allopurinol response - Efficacy Ovarian Neoplasms
Reversed 1
HGVS NC_000004.11:g.89052323G>T
CLNSRC OMIM Allelic Variant PharmGKB Clinical Annotation UniProtKB (protein)
CLNACC RCV000023341.2, RCV000023342.2, RCV000211355.1, RCV000417178.1, RCV000419593.1,

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

[PMID 26552468OA-icon.png] 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.

[PMID 28462920OA-icon.png] Evaluating the association of single-nucleotide polymorphisms with tenofovir exposure in a diverse prospective cohort of women living with HIV.

[PMID 28524801] Association of UGT2B7, UGT1A9, ABCG2, and IL23R polymorphisms with rejection risk in kidney transplant patients.

[PMID 30197413OA-icon.png] Polymorphism of ABCG2 Gene in Hyperuricemia Patients of Han And Uygur Ethnicity with Phlegm/Non-Phlegm Block in Xinjiang, China.

[PMID 30305239] Genetic contributors to serum uric acid levels in Mexicans and their effect on premature coronary artery disease.

[PMID 30519074OA-icon.png] Genetic polymorphism of the methotrexate transporter ABCG2, blood pressure and markers of arterial function in patients with rheumatoid arthritis: repeated cross-sectional study.

[PMID 30899057OA-icon.png] Integrative Genome-Wide Association Studies of eQTL and GWAS Data for Gout Disease Susceptibility.

[PMID 30924303] Gout and the risk of Alzheimer's disease: A Mendelian randomization study.

[PMID 31367212OA-icon.png] ABCG2 gene polymorphism rs2231142 is associated with gout comorbidities but not allopurinol response in primary gout patients of a Chinese Han male population.

[PMID 31391850OA-icon.png] Role of Four ABC Transporter Genes in Pharmacogenetic Susceptibility to Breast Cancer in Jordanian Patients.

[PMID 32183743OA-icon.png] ABCG2 rs2231142 variant in hyperuricemia is modified by SLC2A9 and SLC22A12 polymorphisms and cardiovascular risk factors in an elderly community-dwelling population.