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


OBJECTIVE
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 varepsilon4, 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.


CONCLUSIONS
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.
Jeannesson
Elise
E
Equipe Génétique Cardiovasculaire, INSERM, CIC 9501, Nancy, 54000, France.
Siest
Gérard
G
Zaiou
Mohamed
M
Berrahmoune
Hind
H
Masson
Christine
C
Visvikis-Siest
Sophie
S
D053327:Apolipoprotein E4 / Q000235:genetics; D001794:Blood Pressure / Q000235:genetics; D018938:Caco-2 Cells; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D002319:Cardiovascular System / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002460:Cell Line; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D018922:HL-60 Cells; D056945:Hep G2 Cells; D006801:Humans; D007249:Inflammation / Q000235:genetics; D020014:K562 Cells; D050356:Lipid Metabolism / Q000235:genetics; D008955:Models, Cardiovascular; D009928:Organ Specificity; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D011110:Polymorphism, Genetic; D020298:U937 Cells
D053327:Apolipoprotein E4; C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A