ArticlePharmacogenetics and genomics2018
Differential effect of ABCB1 haplotypes on promoter activity.
Article in Pharmacogenetics and genomics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 10 citations in OpenAlex.
- Article
- Appropriate citation of placenta cell lines 3A(tPA-30-1) and 3A-sub E [post crisis of 3A(tPA-30-1)] in medical literature.Heliyon · 2020Article
- Effect of genetic polymorphisms in CYP3A4, CYP3A5, and m-TOR on everolimus blood exposure and clinical outcomes in cancer patients.The pharmacogenomics journal · 2020Observational
- FKBP1A rs6041749 polymorphism is associated with allograft function in renal transplant patients.European journal of clinical pharmacology · 2019Article
- Promoter Haplotypes of the ABCB1 Gene Encoding the P-Glycoprotein Differentially Affect Its Promoter Activity by Altering Transcription Factor Binding.DNA and cell biology · 2018Article
- Bisphenol A (BPA) and bisphenol S (BPS) alter the promoter activity of the ABCB1 gene encoding P-glycoprotein in the human placenta in a haplotype-dependent manner.Toxicology and applied pharmacology · 2018Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
objectivePromoter single-nucleotide polymorphisms (SNPs) of the ABCB1 gene, encoding the placental efflux transporter P-glycoprotein, can affect its expression and alter xenobiotic transfer from the maternal to the fetal circulation. Because SNPs are arranged in specific combinations as defined haplotypes, the aims of this study were to: (i) determine the placental haplotype structure of the ABCB1 promoter and (ii) determine the differential effect of these haplotypes on placental ABCB1 promoter activity. MATERIALS AND
methodsDNA samples from 100 healthy placentas were PCR-amplified and sequenced to identify existing SNPs in the proximal ABCB1 promoter. The haplotype structure encompassing these SNPs was inferred by PHASE analysis. Luciferase reporter constructs representing these haplotypes were generated and transfected into human placental 3A cells and their effect on ABCB1 promoter activity was determined using a dual-luciferase assay.
resultsWe identified 12 ABCB1 promoter SNPs. These SNPs were predicted by PHASE to segregate into 28 haplotypes with frequencies ranging between 0.019 and 0.88. We found 12 of these haplotypes in our population in addition to two haplotypes not predicted by PHASE. We also generated two haplotypes to determine individual SNP effects for a total of 16 studied. Compared with the ancestral haplotype, three haplotypes significantly up-regulated (107-266% increase; P<0.05), one significantly down-regulated (95.4% decrease; P<0.01), and 12 had no statistically significant effect on ABCB1 promoter activity. DISCUSSION AND
conclusionOur data show that the effect of SNPs on promoter activity depends on their presence in a specific haplotype. This indicates that haplotypes, rather than individual SNPs, could play a significant role in regulating placental P-glycoprotein expression and affect placental transfer and fetal exposure to xenobiotics.
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