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Human Molecular Genetics, 2003, Vol. 12, No. 4 435-439
© 2003 Oxford University Press

Interaction between blood pressure quantitative trait loci in rats in which trait variation at chromosome 1 is conditional upon a specific allele at chromosome 10

Jan Monti1,2, Ralph Plehm1, Herbert Schulz1,3, Detlev Ganten1,3, Reinhold Kreutz3 and Norbert Hübner1,3,*

1Max-Delbrück-Center for Molecular Medicine (MDC), Berlin-Buch, Germany, 2Franz-Volhard-Clinic, HELIOS-Klinikum, Charite, Humboldt-University Berlin, Germany and 3Department of Clinical Pharmacology, Freie University Berlin, Germany

Received November 18, 2002; Accepted December 17, 2002

We have used inbred and congenic rat strains in F2 segregation studies to discover epistasis in a polygenic model of hypertension. Previously, we have found evidence that the presence of a blood pressure quantitative trait locus (QTL) on chromosome 1 is conditional upon the allele status of chromosome 10. To prove the existence of an epistatic interaction we have analyzed congenic strains for chromosome 1 and 10 carrying high blood pressure QTL alleles from the spontaneously hypertensive rat on a normotensive background of the Wistar–Kyoto (WKY) rat. Additionally, a double congenic strain was developed with both chromosome 1 and 10 high blood pressure QTL alleles on the WKY background. Analysis of variance for blood pressure phenotypes as determined by radiotelemetry showed a significant effect for chromosome 10 but not chromosome 1 QTL alleles and demonstrated a significant interaction between the two loci (P<0.05). The interaction accounted for 5 mmHg of blood pressure. Thus, the identification of epistasis is critical to the understanding of the quantitative nature of blood pressure genetics.

* To whom correspondence should be addressed at: Max-Delbrück-Center for Molecular Medicine (MDC), Robert-Rössle-Str. 10, 13092 Berlin, Germany. Tel: +49 3094062530; Fax: +49 3094062110; Email: nhuebner{at}mdc-berlin.de


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