Distinct QTLs are linked to cardiac left ventricular mass in a sex-specific manner in a normotensive inbred rat intercross

Abstract

Genetic mapping of the progeny of an F2 intercross between WKY and WKHA rats had previously allowed us to detect male-specific linkage between locus Cm24 and left ventricular mass index (LVMI). By further expanding that analysis, we detected additional loci that were all linked to LVMI in a sexspecific manner despite their autosomal location. In males, we detected one additional locus (Lvm8) on Chromosome 5 (LOD = 3.4), the two loci Lvm13 (LOD = 4.5) and Lvm9 (LOD = 2.8) on Chromosome 17, and locus Lvm10 (LOD = 4.2) on Chromosome 12. The locus Lvm13 had the same boundaries as locus Cm26 previously reported by others using a different cross. None of these loci showed linkage to LVM in females. In contrast, we identified in females the novel locus Lvm11 on Chromosome 15 (LOD = 2.8) and locus Lvm12 (LOD = 2.7) that had the same boundaries on Chromosome 3 as locus Cm25 detected previously by others using a cross of other normotensive strains. In prepubertal males, there were no differences in the width of cardiomyocytes from WKY and WKHA rats, but cardiomyocytes from WKHA became progressively wider than that of WKY as sexual maturation progressed. Altogether, these results provide evidence that distinct genes may influence LVMI of rats in a sexdependent manner, maybe by involving sex-specific interactions of sex steroids with particular genes involved in the determination of LVMI and/or cardiomyocyte width.