ArticleThe Journal of pharmacology and experimental therapeutics2009
Functional genetic variation in the basal promoter of the organic cation/carnitine transporters OCTN1 (SLC22A4) and OCTN2 (SLC22A5).
Article in The Journal of pharmacology and experimental therapeutics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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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
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- Contribution of the IBD5 locus to inflammatory bowel disease: a meta-analysis.Human genetics · 2011Pooled it
- Kidney function as a key driver of the pharmacokinetic response to high-dose L-carnitine in septic shock.Pharmacotherapy · 2023Trial
- The Human OCTN Sub-Family: Gene and Protein Structure, Expression, and Regulation.International journal of molecular sciences · 2024Review
- The Role of Organic Cation Transporters in the Pharmacokinetics, Pharmacodynamics and Drug-Drug Interactions of Tyrosine Kinase Inhibitors.International journal of molecular sciences · 2023Review
- Identification of critical genetic variants associated with metabolic phenotypes of the Japanese population.Communications biology · 2020Article
- Using l-Carnitine as a Pharmacologic Probe of the Interpatient and Metabolic Variability of Sepsis.Pharmacotherapy · 2020Article
- Impact of Promoter Polymorphisms on the Transcriptional Regulation of the Organic Cation Transporter OCT1 (SLC22A1).Journal of personalized medicine · 2018Article
- ABC transporter polymorphisms are associated with irinotecan pharmacokinetics and neutropenia.The pharmacogenomics journal · 2018Article
- Association study betweenThe Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2017Article
- Identification of OCTN2 variants and their association with phenotypes of Crohn's disease in a Korean population.Scientific reports · 2016Article
- Identification and Functional Characterization of Novel Genetic Variations in the OCTN1 Promoter.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2014Article
- Residual OCTN2 transporter activity, carnitine levels and symptoms correlate in patients with primary carnitine deficiency.Molecular genetics and metabolism reports · 2014Article
- Reduced renal clearance of cefotaxime in asians with a low-frequency polymorphism of OAT3 (SLC22A8).Journal of pharmaceutical sciences · 2013Article
- Genetic and epigenetic regulation of the organic cation transporter 3, SLC22A3.The pharmacogenomics journal · 2013Article
- Discovery of regulatory elements in human ATP-binding cassette transporters through expression quantitative trait mapping.The pharmacogenomics journal · 2012Article
- Functional characterization of liver enhancers that regulate drug-associated transporters.Clinical pharmacology and therapeutics · 2011Article
- Pharmacogenomics of membrane transporters: past, present and future.Pharmacogenomics · 2010Article
- The pharmacogenomics of membrane transporters project: research at the interface of genomics and transporter pharmacology.Clinical pharmacology and therapeutics · 2010Review
- Pharmacogenomic discovery using cell-based models.Pharmacological reviews · 2009Review
- Institutional Profile: The University of California Pharmacogenomics Center: at the interface of genomics, biological mechanisms and drug therapy.Pharmacogenomics · 2009Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
The organic cation/ergothioneine transporter OCTN1 (SLC22A4) and the high-affinity carnitine transporter OCTN2 (SLC22A5), play an important role in the disposition of xenobiotics and endogenous compounds. Here, we analyzed the sequence of the proximal promoter regions of OCTN1 and OCTN2 in four ethnic groups and determined the effects of the identified genetic variants on transcriptional activities and mRNA expression. Six variants were found in the proximal promoter of OCTN1, one of which showed high allele frequency ranging from 13 to 34% in samples from individuals with ancestries in Africa, Europe, China, and Mexico. OCTN1 haplotypes had similar activities as the reference in luciferase reporter assays. For OCTN2, three of the seven variants identified in the proximal promoter showed allele frequencies greater than 29.5% in all populations, with the exception of -207C>G (rs2631367) that was monomorphic in Asian Americans. OCTN2 haplotypes containing -207G, present in all populations, were associated with a gain of function in luciferase reporter assays. Consistent with reporter assays, OCTN2 mRNA expression levels in lymphoblastoid cell lines (LCLs) from gene expression analysis were greater in samples carrying a marker for -207G. This SNP seems to contribute to racial differences in OCTN2 mRNA expression levels in LCLs. Our study with healthy subjects (n = 16) homozygous for either -207C or -207G, showed no appreciable effect of this SNP on carnitine disposition. However, there were significant effects of gender on carnitine plasma levels (p < 0.01). Further in vivo studies of OCTN2 promoter variants on carnitine disposition and variation in drug response are warranted.
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Registered trials
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