Open Access Highly Accessed Research article

Epistatic study reveals two genetic interactions in blood pressure regulation

Ndeye Coumba Ndiaye1, El Shamieh Said1, Maria G Stathopoulou1, Gérard Siest1, Michael Y Tsai2 and Sophie Visvikis-Siest13*

Author affiliations

1 “Cardiovascular Genetics” Research Unit, EA-4373, University of Lorraine, 30 rue Lionnois – 54000, Nancy, France

2 Department of Laboratory Medicine & Pathology, University of Minnesota, Minneapolis, MN, 55455-0392, USA

3 Department of Internal Medicine and Geriatrics, CHU Nancy-Brabois, France

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Citation and License

BMC Medical Genetics 2013, 14:2  doi:10.1186/1471-2350-14-2

Published: 8 January 2013



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.


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.


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.


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.

Blood pressure; Epistasis; Single nucleotide polymorphism; Epidemiology