ArticlePharmacogenetics and genomics2016
CYP3A4 intronic SNP rs35599367 (CYP3A4*22) alters RNA splicing.
Article in Pharmacogenetics and genomics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
63 citing papers in PubMed, 3 syntheses or guidelines pooled it, 103 citations in OpenAlex.
- CYP3A4*22 Genotype-Guided Dosing of Kinase Inhibitors in Cancer Patients.Clinical pharmacokinetics · 2023Pooled it
- Effects ofFrontiers in pharmacology · 2023Pooled it
- Genomewide Association Study of Simvastatin Pharmacokinetics.Clinical pharmacology and therapeutics · 2022Pooled it
- Influence of CYP2B6 activity score on the pharmacokinetics and safety of single dose efavirenz in healthy volunteers.The pharmacogenomics journal · 2020Trial
- Effects of the MAML2 genetic variants in glioma susceptibility and prognosis.Bioscience reports · 2019Trial
- Synergistic Effects of Inflammation and Drug Interactions onPharmaceutics · 2026Article
- Candidate-gene-based study of CYP3A-related single-nucleotide polymorphisms using 4β-hydroxycholesterol/cholesterol ratio as biomarker in a Japanese cohort.European journal of clinical pharmacology · 2026Article
- From Genotype to Functional Risk: A Multi-Omic Approach to Predicting Thiopurine and Methotrexate Co-Therapy-Induced Liver Injury.Pharmaceuticals (Basel, Switzerland) · 2026Review
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- Susceptibility to childhood asthma modified by the interactive effects of polycyclic aromatic hydrocarbons exposure and genetic polymorphisms of the aryl hydrocarbon receptor signaling pathway: functional analysis based on lipid metabolism.Respiratory research · 2025Article
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- Genetic Modulation of Silodosin Exposure and Efficacy: The Role of CYP3A4, CYP3A5, and UGT2B7 Polymorphisms in Benign Prostatic Hyperplasia Management.Journal of personalized medicine · 2025Article
- Mechanism of Myh3 gene regulation of intramuscular fat content in Beijing black pigs via the MAPK signaling pathway.BMC genomics · 2025Article
- Association analysis of PAEP, KRT10, and BMP7 genes SNPs with reproductive traits in Kele pigs.PloS one · 2025Article
- Assessment of MIR3142HG genetic polymorphisms and the susceptibility of lumbar disc herniation in the Chinese population.Scientific reports · 2024Article
- DNA Methylation in the CYP3A Distal Regulatory Region (DRR) Is Associated with the Expression of CYP3A5 and CYP3A7 in Human Liver Samples.Molecules (Basel, Switzerland) · 2024Article
- Steroid-tacrolimus drug-drug interaction and the effect of CYP3A genotypes.British journal of clinical pharmacology · 2024Article
- Assessing Pharmacogenomic loci Associated with the Pharmacokinetics of Vamorolone in Boys with Duchenne Muscular Dystrophy.Journal of clinical pharmacology · 2024Article
- Genetic characterization of theParasitology · 2024Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 2 countries.
Funding
Abstract
Cytochrome P450 3A4 (CYP3A4) metabolizes 30-50% of clinically used drugs. Large interperson variability in CYP3A4 activity affects response to CYP3A4 substrate drugs. We had demonstrated that an intronic single nucleotide polymorphism rs35599367 (CYP3A4*22, located in intron 6) reduces mRNA/protein expression; however, the underlying mechanism remained unknown. Here we show that CYP3A4*22 is associated with a two-fold or greater increase in formation of a nonfunctional CYP3A4 alternative splice variant with partial intron 6 retention in human liver (P=0.006), but not in small intestines. Consistent with this observation, in-vitro transfection experiments with a CYP3A4 minigene (spanning from intron 5 to intron 7) demonstrated that plasmids carrying the rs35599367 minor T allele caused significantly greater intron 6 retention than the C allele in liver derived HepG2 cells, but not in intestine-derived LS-174T cells. These results indicate that tissue-specific increased formation of nonfunctional alternative splice variant causes reduced CYP3A4 mRNA/protein expression in CYP3A4*22 carriers.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.