The Y chromosome - Epistatic and ecogenetic interactions in genetic hypertension

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 approximate to 16 mm Hg difference in systolic BP (P < 10(-7)) at baseline but not after dietary salt loading (P = .82) between F-2 males derived from an SHRSP(HD) grandfather and a Wistar-Kyoto (WKYHD-0) grandmother and F-2 males from a reciprocal cross (WKYHD-0 grandfather). When we examined F-2 animals from reciprocal crosses between SHRSP(HD) and a congenic strain, WKYHD-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-la), we found no significant differences either at baseline (P = .39) or after salt loading (P = .51) in the two reciprocal F-2 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-la and reciprocal cross status on BP in the two crosses. In the F-2 (WKYHD-OxSHRSP(HD)) cross, no significant interaction was found for basal systolic BP (P = .89), arguing against a major influence of BP/SP-la on the Y-chromosome effects on basal BP. However, a significant interaction between zygosity at the BP/SP-la locus and reciprocal cross status for systolic BP after salt loading (P = .022) indicated that the BP/SP-la-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.