INDEPENDENT GENETIC SUSCEPTIBILITY TO CARDIAC-HYPERTROPHY IN INHERITED HYPERTENSION

Cardiac hypertrophy is a common but not inevitable complication of hyp ertension. Variation in heart size in hypertensives may reflect indepe ndent genetic susceptibility to cardiac hypertrophy. Using an experime ntal genetic model, we determined the location of quantitative trait l oci responsible for cardiac hypertrophy and/or hypertension. We studie d 182 F-2 male animals derived from a cross of the spontaneously hyper tensive rat and normotensive Donryu rats. Direct mean arterial pressur e (MAP) and left ventricular (LV) mas were measured at 20 weeks of age , and DNA was obtained for linkage analysis. The estimated heritabilit y of MAP was 62% and for LV mass expressed per unit of body weight (re lative LV mass) was 76%. We used 185 polymorphic markers, with an aver age intermarker distance of 12.3 centimorgans for a genome-wide scan i n a representative subgroup of 46 animals to identify preliminary quan titative trait loci, which were then mapped in all 182 male F-2 rats. Two loci showed logarithm of the odds scores of >4.0. One on chromosom e 2, Lvm-1, was linked to relative LV mass but showed no evidence of l inkage to MAP. Another locus on chromosome 1, Map-1, was linked to MAP . In the same region, a locus Lvm-2 was linked with relative LV mass. These data indicate the existence of a genetic locus on chromosome 2 o f the spontaneously hypertensive rat that affects relative LV mass ind ependently of blood pressure.