Evidence map›Paper›PMID 25750709›Full record

ArticleBiology of sex differences2015

Expression of drug transporters in human kidney: impact of sex, age, and ethnicity.

Stancy Joseph, Tamara J Nicolson, George Hammons, Beverly Word, Bridgett Green-Knox, Beverly Lyn-Cook

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biology of sex differences, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed, 1 pooled it
2.0field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

41 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Stancy JosephDivision of Biochemical Toxicology, National Center for Toxicological Research, Food and Drug Administration, Building 50, Room 630, HFT 100, 3900 NCTR Road, Jefferson, AR 72079 USA.
Tamara J NicolsonDrug Discovery and Development, London, UK.
George HammonsDivision of Biochemical Toxicology, National Center for Toxicological Research, Food and Drug Administration, Building 50, Room 630, HFT 100, 3900 NCTR Road, Jefferson, AR 72079 USA.
Beverly WordDivision of Biochemical Toxicology, National Center for Toxicological Research, Food and Drug Administration, Building 50, Room 630, HFT 100, 3900 NCTR Road, Jefferson, AR 72079 USA.
Bridgett Green-KnoxDivison of Systems Biology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR 72079-9502 USA.
Beverly Lyn-CookDivision of Biochemical Toxicology, National Center for Toxicological Research, Food and Drug Administration, Building 50, Room 630, HFT 100, 3900 NCTR Road, Jefferson, AR 72079 USA.
National Center for Toxicological Research · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundDifferences in expression of drug transporters in human kidney contribute to changes in pharmacokinetics and toxicokinetics of a variety of drug compounds. The basal expression levels of genes involved in drug transport processes in the kidney introduces differences in bioavailability, distribution, and clearance of drugs, possibly influencing drug efficacy and adverse reactions. Sex differences in gene expression of transporters are a key cause of differences in sex-dependent pharmacokinetics, which may characterize many drugs and contribute to individual differences in drug efficacy and toxicity. Therefore, evaluating the expression of drug transporters in normal human kidneys is important to better understand differences in drug bioavailability, distribution, and clearance of drugs in humans. Other factors such as age and ethnicity may also contribute to individual differences in gene expression of drug transporters in the human kidney.

methodsQuantitative real-time PCR (QRT-PCR) was performed to determine the gene expression of 30 drug transporters in 95 age-matched normal human kidney tissues. Multiple Student's t-tests (Sidak-Bonferroni correction) and two-way ANOVA (Bonferroni correction) analyses were used to determine statistically significant differences.

resultsIn the 30 transporter genes examined, sex, ethnicity, and age differences in gene expression were exhibited in normal human kidney tissue. These changes in expression were not found to be differentially significant. However, sex-age and sex-ethnicity interactions were found to be statistically significant. For sex-age interactions, SCL22A12 was found to be significantly higher expressed in females <50 years compared to males <50 years. Expression levels of SLC22A2, SLC22A12, SLC6A16, and ABCB6 were significantly higher in females <50 years compared to females ≥50 years. In sex-ethnicity interactions, expression levels of ATP7B and KCNJ8 were found to be significantly higher in African American females compared to European American females. Also, the expression of SLC31A2 was significantly higher in European American males compared to European American females.

conclusionsSex, age, and ethnic differences impacted the expression of drug transporters in normal human kidneys, which suggests that the analysis of gene expression of drug transporters will aid in improving the usage/dosage of drug therapies influencing personalized medicine and susceptibility to adverse drug reactions.

Indexed as

AgeATP-binding cassettes (ABCs)Drug transportersEthnicityGene expressionKidneySex differenceSolute carriers (SLCs)

Identifiers

PMID25750709
PMCPMC4352278
OpenAlexW2160859703

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Registered trials

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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.