X-linked locus associated with hypertensive renal disease susceptibility in Dahl rats.
OBJECTIVE
There is increasing evidence that genetic factors contribute to renal disease susceptibility associated with essential hypertension. To what extent these genetic factors act independently of hypertension susceptibility remains undetermined. The present study was undertaken to assess the potential chromosome X influence on target organ renal disease in the Dahl rat model of salt-sensitive hypertension.


METHODS
Dahl S, Dahl R, F1(RXS), F1(SXR) and F2(RXS) rat male populations were phenotyped for hypertensive renal disease by measuring the percent of incidence of the Grade IV Raij renal pathology score. Six chromosome X markers informative for our (RXS) intercross were analyzed in our F2 rat population (n = 105) for co-segregation with hypertensive renal disease and blood pressure characterized by radiotelemetry.


RESULTS
Comparison of the incidence of renal disease (histologically determined) between F1 reciprocal intercross male progenies reveals a significant chromosome X effect on renal disease [percent incidence of Grade IV Raij renal pathology score in F1 (R female S male) male rats = 2.75 +/- 0.66, and in F1 (S female R male) male rats = 0.67 +/- 0.42; = 0.02]. QTL analysis on an F2(RXS) male population phenotyped for renal disease susceptibility (percent incidence of Grade IV Raij renal pathology score) detects significant linkage to DXRat98 (likelihood ratio statistic = 9.4, P = 0.00223) on chromosome X, corroborating X-linkage of renal disease susceptibility in Dahl rats.


CONCLUSIONS
Our results demonstrate the existence of an X-linked locus associated with hypertensive renal disease susceptibility in Dahl rats. Furthermore, the chromosome X markers tested did not co-segregate with hypertension, indicating that the gene(s) on chromosome X influence renal disease susceptibility independent of blood pressure.
Herrera
Victoria L M
VL
Section of Molecular Medicine, Department of Medicine, Boston University School of Medicine, 700 Albany Street, Boston, MA 02118, USA.
Traverse
Sarah
S
Lopez
Lyle V
LV
Ruiz-Opazo
Nelson
N
D000818:Animals; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006824:Hybridization, Genetic; D006973:Hypertension / Q000150:complications*; D007668:Kidney / Q000473:pathology; D007674:Kidney Diseases / Q000209:etiology* / Q000235:genetics* / Q000473:pathology; D008297:Male; D051381:Rats; D020303:Rats, Inbred Dahl / Q000235:genetics; D014960:X Chromosome