rs35599367

This is a intronic variant in the CYP3A4 gene.

Key Literature Trait Associations

Tacrolimus Metabolism

CYP3A4*22 is an intron 6 variant that reduces CYP3A4 mRNA expression by approximately 50%, leading to slower metabolism of many drugs. Carriers require lower doses of tacrolimus, statins (particularly atorvastatin and simvastatin), and other CYP3A4 substrates. This variant is included in the Dutch Pharmacogenetics Working Group (DPWG) guidelines for statin dosing adjustments.

Birdwell KA et al. “Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP3A5 Genotype and Tacrolimus Dosing.” Clinical Pharmacology and Therapeutics 98(1):19-24 (2015)
Allele T
OR —
p —
Candidate gene study
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GWAS Catalog Trait Associations (4)

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

glycohyocholate 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 A
OR 0.28
p 2.0e-27
N 14,296
Large GWAS
European

X-17357 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 A
OR 0.23
p 2.0e-22
N 14,296
Large GWAS
European
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Research that mentions this SNP (3)

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Association of single nucleotide polymorphisms in IL8 and IL13 with sunitinib-induced toxicity in patients with metastatic renal cell carcinoma
AssociationN=374Meta H. M. Diekstra et al.(2015)· European Journal of Clinical Pharmacology

This pharmacogenetic study of 374 patients with metastatic renal cell carcinoma examined SNP associations with sunitinib-induced toxicity. The IL8 rs1126647 T allele was associated with increased hypertension risk (OR=1.69, P=0.024), and the IL13 rs1800925 T allele was associated with increased leukopenia (OR=6.76, P=0.020) and grade >2 toxicity (OR=1.75, P=0.028). No significant associations were found with progression-free survival, overall survival, or clinical response.

Traits studied:Clinical responseGrade 2+ toxicityHand-foot syndromeHypertensionLeukopeniaMetastatic renal cell carcinomaMucosal inflammationOverall survivalProgression-free survivalSunitinib-induced toxicityThrombocytopenia
PubMedDOIMetascience Observatory
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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
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The effects of CYP3A4, CYP3A5, ABCB1, ABCC2, ABCG2 and SLCO1B3 single nucleotide polymorphisms on the pharmacokinetics and pharmacodynamics of docetaxel in nasopharyngeal carcinoma patients
AssociationN=54Sin-Chi Chew et al.(2011)· Cancer Chemotherapy and Pharmacology

This pharmacogenetic study of 54 Asian nasopharyngeal cancer patients examined how polymorphisms in CYP3A4, CYP3A5, ABCB1, ABCC2, ABCG2, and SLCO1B3 affect docetaxel pharmacokinetics and toxicity. Patients homozygous for the variant allele (GG) of SLCO1B3 rs11045585 had significantly higher AUC and lower clearance of docetaxel (P = 0.026 and P = 0.036, respectively). ABCB1 heterozygotes showed the highest decrease in nadir hemoglobin (P = 0.006). The study suggests functional polymorphisms in SLCO1B3 and ABCB1 cooperatively influence docetaxel disposition.

Traits studied:Docetaxel pharmacokineticsDocetaxel toxicityHematological toxicityNasopharyngeal carcinomaNon-hematological toxicity
PubMedDOIMetascience Observatory

Gene information from NCBI Gene. Variant classifications from ClinVar.

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