rs887829

This is a regulatory variant in the UGT1A1 gene.

Key Literature Trait Associations

Irinotecan Toxicity

UGT1A1*80 is a regulatory variant in perfect linkage disequilibrium with UGT1A1*28 (the TA repeat polymorphism). It reduces UGT1A1 expression, impairing glucuronidation of SN-38, the active metabolite of the chemotherapy drug irinotecan. Homozygous carriers have Gilbert syndrome and face severe neutropenia and diarrhea from standard irinotecan doses. CPIC recommends a reduced starting dose of irinotecan for UGT1A1 poor metabolizers (*28/*28 or *80/*80).

Spittle AJ et al. “Motor impairments in children: More than just the clumsy child.” Journal of Paediatrics and Child Health 54(10):1131-1135 (2018)
Allele T
OR —
p —
Candidate gene study
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GWAS Catalog Trait Associations (28)

Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.

biliverdin measurement

Yin X et al. “Genome-wide association studies of metabolites in Finnish men identify disease-relevant loci.” Nature Communications 13(1):1644 (2022)
Allele T
OR 0.70
p —
N 6,136
Large GWAS
European
Shin SY et al. “An atlas of genetic influences on human blood metabolites.” Nature Genetics 46(6):543-550 (2014)
Allele T
OR 0.11
p 3.0e-168
N 6,686
Large GWAS
European
Schlosser P et al. “Genetic studies of paired metabolomes reveal enzymatic and transport processes at the interface of plasma and urine.” Nature Genetics 55(6):995-1008 (2023)
Allele T
OR 0.43
p 4.0e-185
N 4,956
Large GWAS
European
Tahir UA et al. “Whole Genome Association Study of the Plasma Metabolome Identifies Metabolites Linked to Cardiometabolic Disease in Black Individuals.” Nature Communications 13(1):4923 (2022)
Allele T
OR 0.62
p 8.0e-100
N 2,466
Large GWAS
multi-ancestry
Liu C et al. “Crosstalk between Host Genome and Metabolome among People with HIV in South Africa.” Metabolites 12(7) (2022)
Allele T
OR 0.39
p 1.0e-8
N 998
Small GWAS
Sub-Saharan African

Succinimide measurement

Surendran P et al. “Rare and common genetic determinants of metabolic individuality and their effects on human health.” Nature Medicine 28(11):2321-2332 (2022)
Allele T
OR 0.44
p —
N 14,296
Large GWAS
European

X-16946 measurement

Surendran P et al. “Rare and common genetic determinants of metabolic individuality and their effects on human health.” Nature Medicine 28(11):2321-2332 (2022)
Allele T
OR 0.52
p —
N 14,296
Large GWAS
European
Yin X et al. “Genome-wide association studies of metabolites in Finnish men identify disease-relevant loci.” Nature Communications 13(1):1644 (2022)
Allele T
OR 0.65
p 3.0e-294
N 6,136
Large GWAS
European

X-24849 measurement

Hysi PG et al. “Metabolome Genome-Wide Association Study Identifies 74 Novel Genomic Regions Influencing Plasma Metabolites Levels.” Metabolites 12(1) (2022)
Allele T
OR 0.57
p 1.0e-300
N 8,809
Large GWAS
European
Yin X et al. “Genome-wide association studies of metabolites in Finnish men identify disease-relevant loci.” Nature Communications 13(1):1644 (2022)
Allele T
OR 0.66
p 8.0e-300
N 6,136
Large GWAS
European

X-11530 measurement

Yin X et al. “Genome-wide association studies of metabolites in Finnish men identify disease-relevant loci.” Nature Communications 13(1):1644 (2022)
Allele T
OR 0.65
p 3.0e-298
N 6,136
Large GWAS
European
Shin SY et al. “An atlas of genetic influences on human blood metabolites.” Nature Genetics 46(6):543-550 (2014)
Allele T
OR 0.11
p 2.0e-140
N 7,409
Large GWAS
European

X-11522 measurement

Yin X et al. “Genome-wide association studies of metabolites in Finnish men identify disease-relevant loci.” Nature Communications 13(1):1644 (2022)
Allele T
OR 0.65
p 8.0e-295
N 6,136
Large GWAS
European

X-21448 measurement

Yin X et al. “Genome-wide association studies of metabolites in Finnish men identify disease-relevant loci.” Nature Communications 13(1):1644 (2022)
Allele T
OR 0.64
p 2.0e-287
N 6,136
Large GWAS
European

X-11442 measurement

Surendran P et al. “Rare and common genetic determinants of metabolic individuality and their effects on human health.” Nature Medicine 28(11):2321-2332 (2022)
Allele T
OR 0.38
p 2.0e-253
N 14,296
Large GWAS
European
Yin X et al. “Genome-wide association studies of metabolites in Finnish men identify disease-relevant loci.” Nature Communications 13(1):1644 (2022)
Allele T
OR 0.44
p 4.0e-131
N 6,136
Large GWAS
European

X-11441 measurement

Surendran P et al. “Rare and common genetic determinants of metabolic individuality and their effects on human health.” Nature Medicine 28(11):2321-2332 (2022)
Allele T
OR 0.36
p 2.0e-221
N 14,296
Large GWAS
European
Yin X et al. “Genome-wide association studies of metabolites in Finnish men identify disease-relevant loci.” Nature Communications 13(1):1644 (2022)
Allele T
OR 0.43
p 5.0e-124
N 6,136
Large GWAS
European

serum metabolite level

Feofanova EV et al. “A Genome-wide Association Study Discovers 46 Loci of the Human Metabolome in the Hispanic Community Health Study/Study of Latinos.” American Journal of Human Genetics 107(5):849-863 (2020)
Allele C
OR 0.68
p 4.0e-175
N 3,926
Large GWAS
Hispanic or Latin American
Yu B et al. “Genetic determinants influencing human serum metabolome among African Americans.” Plos Genetics 10(3):e1004212 (2014)
Allele C
OR 0.32
p 1.0e-17
N 1,260
Large GWAS
African American or Afro-Caribbean
▶

Research that mentions this SNP (5)

▶
A Genome‐Wide Association Study for Serum Bilirubin Levels and Gene‐Environment Interaction in a Chinese Population
AssociationN=3,294Xiayun Dai et al.(2013)· Genetic Epidemiology

GWAS study of 3,294 European ancestry individuals from the eMERGE Network examining serum bilirubin and other liver function tests. Strong association signal at UGT1A1 locus (rs887829, beta=0.15, p=1.30×10^-118) confirmed in both adult and pediatric populations. Additional associations identified in SLCO1B1, SLCO1B3, TDRP, ZMYND8, and ABO locus. Phenome-wide analysis revealed protective effect of TA7 repeat against cerebrovascular disease (OR=0.75, p=0.0008).

Traits studied:ALTASTAlkaline phosphataseCerebrovascular diseaseGGTLiver function testsSerum bilirubin levels
PubMedDOIMetascience Observatory
▶
A Genome-Wide Assessment of Variability in Human Serum Metabolism
AssociationN=891Mun-Gwan Hong et al.(2013)· Human Mutation

A genome-wide association study (GWAS) of serum metabolic quantitative trait loci (mQTLs) in 891 Swedish men identified seven replicating loci (PYROXD2, FADS1, PON1, CYP4F2, UGT1A8, ACADL, and LIPC) with variants showing significant associations with metabolite levels (P = 10^-13 to 10^-91). rs4345897:A>G in PYROXD2 showed the strongest association with caprolactam (P = 2.40 × 10^-91), while rs174549:A>G in FADS1 associated with glycerolphosphocholine (P = 1.91 × 10^-30). Pathway analysis implicated genes with acyl-CoA dehydrogenase activity (ACADS, ACADM, ACAD8, ACAD10, ACAD11, ACOXL) and mQTL SNPs were enriched across GWAS catalog regions.

Traits studied:BilirubinButyrylcarnitineCaprolactamDimethylheptanoylcarnitineGlycerolphosphocholineGlycochenodeoxycholic acidHexanoylcarnitineSerum metabolitesStearoylcarnitine
PubMedDOIMetascience Observatory
▶
Interindividual Variability in the Hepatic Expression of the Human Breast Cancer Resistance Protein (BCRP/ABCG2): Effect of Age, Sex, and Genotype
AssociationN=1,000Bhagwat Prasad et al.(2013)· Journal of Pharmaceutical Sciences

Case-control study of 1,000 Han Chinese individuals (450 epilepsy cases, 550 controls) examining associations between STX1B polymorphisms and epilepsy treatment response. The rs140820592 variant showed significant association with reduced epilepsy risk (OR=0.542, p=0.004) and drug-resistant epilepsy risk (OR=0.260, p=0.004), with eQTL analysis confirming rs140820592 regulates STX1B expression in brain tissues.

Traits studied:Drug-resistant epilepsyDrug-responsive epilepsyEpilepsyImatinib response in chronic myelogenous leukemiaPraziquantel responseTacrolimus metabolism
PubMedDOIMetascience Observatory
▶
Influence of neurexin 1 (NRXN1) polymorphisms in clozapine response
ReviewRenan P. Souza et al.(2010)· Human Psychopharmacology: Clinical and Experimental

This systematic review of 98 studies examined biological predictors of clozapine response in treatment-resistant schizophrenia patients. Of 379 different gene variants investigated across 70 genetic studies, only three variants (DRD3 Ser9Gly rs6280, HTR2A His452Tyr, and GNB3 C825T) achieved independent replication. Non-genetic predictors included higher prefrontal cortical volumes and lower HVA:5-HIAA ratio in cerebrospinal fluid.

Traits studied:Clozapine responseSchizophreniaTreatment-resistant schizophrenia
PubMedDOIMetascience Observatory
▶
Lack of association of GPX1 and MnSOD genes with symptom severity and response to clozapine treatment in schizophrenia subjects
ReviewRenan P. Souza et al.(2009)· Human Psychopharmacology: Clinical and Experimental

A systematic review of 98 studies investigating biological predictors of clozapine response in treatment-resistant schizophrenia. Of 70 genetic studies examining 379 variants, only three genetic variants have independently replicated findings: DRD3 Ser9Gly (rs6280), HTR2A His452Tyr, and GNB3 C825T (rs5442/rs5443). Non-genetic predictors include higher prefrontal cortical structural integrity and activity, and lower HVA:5-HIAA ratio in cerebrospinal fluid.

Traits studied:Clozapine responseSchizophreniaTreatment-resistant schizophrenia
PubMedDOIMetascience Observatory

Gene information from NCBI Gene. Variant classifications from ClinVar.

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