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(Hypertension. 1996;28:895-897.)
© 1996 American Heart Association, Inc.

Articles

The Y Chromosome

Epistatic and Ecogenetic Interactions in Genetic Hypertension

Reinhold Kreutz; Philippe Stock; Berthold Struk; Klaus Lindpaintner

the Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, and the Department of Cardiology, Children's Hospital, Harvard Medical School, Boston, Mass.

Correspondence to Klaus Lindpaintner, MD, Cardiovascular Division, Brigham and Women's Hospital, 75 Francis St, Thorn 1103, Boston, MA 02115. E-mail kl@calvin.bwh.harvard.edu.

Previous studies have revealed conflicting evidence concerning a Y-chromosome effect on blood pressure (BP) in genetic crosses involving different strains of spontaneously hypertensive rats (SHR or SHRSP). We had previously found an 16 mm Hg difference in systolic BP (P<10^-7) at baseline but not after dietary salt loading (P=.82) between F₂ males derived from an SHRSP_HD grandfather and a Wistar-Kyoto (WKY_HD-0) grandmother and F₂ males from a reciprocal cross (WKY_HD-0 grandfather). When we examined F₂ animals from reciprocal crosses between SHRSP_HD and a congenic strain, WKY_HD-1, which carries a 6-centimorgan-long SHRSP_HD-homologous genomic fragment on chromosome 10 that contains a quantitative trait locus linked to BP (BP/SP-1a), we found no significant differences either at baseline (P=.39) or after salt loading (P=.51) in the two reciprocal F₂ cohorts. To test the hypothesis that Y-chromosome–autosomal epistasis accounts for the discrepant Y-chromosome effects on BP, we analyzed the interaction between BP/SP-1a and reciprocal cross status on BP in the two crosses. In the F₂ (WKY_HD-0xSHRSP_HD) cross, no significant interaction was found for basal systolic BP (P=.89), arguing against a major influence of BP/SP-1a on the Y-chromosome effects on basal BP. However, a significant interaction between zygosity at the BP/SP-1a locus and reciprocal cross status for systolic BP after salt loading (P=.022) indicated that the BP/SP-1a–SHRSP_HD allele exhibited a significant effect on BP after dietary excess salt only in males that inherited the SHRSP Y chromosome. These results support the relevance of a Y-chromosome effect on BP and suggest that a complex interplay of epistatic and ecogenetic interactions governs its effect on phenotype.

Key Words: genetic hypertension • sex • genes • Wistar-Kyoto rat • spontaneously hypertensive rat

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