Epistatic study reveals two genetic interactions in blood pressure regulation

Ndeye Coumba Ndiaye, El Shamieh Said, Maria G. Stathopoulou, Gérard Siest, Michael Y. Tsai, Sophie Visvikis-Siest

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


Background: Although numerous candidate gene and genome-wide association studies have been performed on blood pressure, a small number of regulating genetic variants having a limited effect have been identified. This phenomenon can partially be explained by possible gene-gene/epistasis interactions that were little investigated so far.Methods: We performed a pre-planned two-phase investigation: in phase 1, one hundred single nucleotide polymorphisms (SNPs) in 65 candidate genes were genotyped in 1,912 French unrelated adults in order to study their two-locus combined effects on blood pressure (BP) levels. In phase 2, the significant epistatic interactions observed in phase 1 were tested in an independent population gathering 1,755 unrelated European adults.Results: Among the 9 genetic variants significantly associated with systolic and diastolic BP in phase 1, some may act through altering the corresponding protein levels: SNPs rs5742910 (Padjusted≤0.03) and rs6046 (Padjusted =0.044) in F7 and rs1800469 (Padjusted ≤0.036) in TGFB1; whereas some may be functional through altering the corresponding protein structure: rs1800590 (Padjusted =0.028, SE=0.088) in LPL and rs2228570 (Padjusted ≤9.48×10-4) in VDR. The two epistatic interactions found for systolic and diastolic BP in the discovery phase: VCAM1 (rs1041163) * APOB (rs1367117), and SCGB1A1 (rs3741240) * LPL (rs1800590), were tested in the replication population and we observed significant interactions on DBP. In silico analyses yielded putative functional properties of the SNPs involved in these epistatic interactions trough the alteration of corresponding protein structures.Conclusions: These findings support the hypothesis that different pathways and then different genes may act synergistically in order to modify BP. This could highlight novel pathophysiologic mechanisms underlying hypertension.

Original languageEnglish (US)
Article number2
JournalBMC medical genetics
Issue number1
StatePublished - Jan 8 2013

Bibliographical note

Funding Information:
The data used are part of the BRC “Interactions Gène-Environnement en Physiopathologie CardioVasculaire” in Nancy, France. The population involved, was supported by the “Caisse Nationale d'Assurance Maladies des Travailleurs Salariés”, the “Institut National de la Santé et de la Recherche Médicale” (INSERM), the “Région Lorraine”, the “Communauté Urbaine du Grand Nancy,” and the University of Lorraine. We are deeply grateful for the cooperation of the individuals participating in the study sample. We are grateful to Roche molecular system Alameda (California, USA) for their support in the Mutiplex assay genotyping and we thank Christine Masson for her participation in the performance of the Multiplex genotyping. Finally, this project is realized thanks to the Bio-intelligence project.


  • Blood pressure
  • Epidemiology
  • Epistasis
  • Single nucleotide polymorphism


Dive into the research topics of 'Epistatic study reveals two genetic interactions in blood pressure regulation'. Together they form a unique fingerprint.

Cite this