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Genetic profiling of human cell lines used as in vitro model to study cardiovascular pathophysiology and pharmacotoxicology

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Abstract

Background

Cell lines are widely used to monitor drug pharmacokinetics and pharmacodynamics and to investigate a number of biochemical mechanisms. However, little is known about the genetic profile of these in vitro models.

Objectives

To analyze genetic profile of Thp1, U937, HL60, K562, HepG2, Kyn2, and Caco2 human cell lines with a focus on genetic variations within genes involved in the development of cardiovascular pathologies and drug treatment response.

Methods

Multiplex polymerase chain reaction (PCR), PCR–restriction fragment length polymorphism and TaqMan assays were used to genotype 120 polymorphisms within 68 genes previously shown to be involved in various processes such as inflammation, lipid metabolism, and blood pressure.

Results

We provide here a list of potential polymorphisms known to be associated with cardiovascular disease. Our results show that the seven cell lines examined carry several of these mutations within genes of interest. Due to the abundance of these variations, only two examples will be given in this abstract. For instance, U937 cells are homozygous for APOE ɛ4, a mutant associated with higher susceptibility to cardiovascular diseases and lower response to statins. Our study also showed that deletion in intron 16 of the ACE gene, which is associated with susceptibility to hypertension and variation of response to ACE inhibitors, can be found in all considered cells but Kyn2 cells.

Conclusion

We provide here a data bank of different cell lines genetic profile. In our opinion, this useful information may bring insights into the design and choice of an adequate in vitro model and may help to explain mysterious discrepancies in data from different laboratories.

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Acknowledgments

We thank Dr Garnotel, Pr Jeannesson, Pr Dauca, and Dr Sabolovic for kindly providing cell lines. We also thank Roche Molecular Systems (Alameda, CA, USA) for providing us material to perform multiplex genotyping analyses.

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Authors and Affiliations

  1. Equipe Génétique Cardiovasculaire, INSERM, CIC 9501, Nancy, 54000, France

    Elise Jeannesson, Gérard Siest, Mohamed Zaiou, Hind Berrahmoune, Christine Masson & Sophie Visvikis-Siest

  2. Faculté de Pharmacie, Nancy-Université, Nancy, 54000, France

    Elise Jeannesson, Gérard Siest, Mohamed Zaiou & Christine Masson

  3. Equipe Inserm Génétique Cardiovasculaire, Faculté de Pharmacie, INSERM-CIC 9501, 30 rue Lionnois, 54000, Nancy, France

    Gérard Siest

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  1. Elise Jeannesson
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  2. Gérard Siest
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  4. Hind Berrahmoune
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Correspondence to Gérard Siest.

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Jeannesson, E., Siest, G., Zaiou, M. et al. Genetic profiling of human cell lines used as in vitro model to study cardiovascular pathophysiology and pharmacotoxicology. Cell Biol Toxicol 25, 561–571 (2009). https://doi.org/10.1007/s10565-008-9112-8

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