Yagil C, Sapojnikov M, Kreutz R, Katni G, Lindpaintner K, Ganten D, Yagil Y
Department of Nephrology and Hypertension, Barzilai Medical Center-Ashkelon, Faculty of Health Sciences, Ben-Gurion University, Israel.
Hypertension. 1998 Jan;31(1):119-24. doi: 10.1161/01.hyp.31.1.119.
Random genome screening was initiated in the Sabra rat model of hypertension in search of genes that account for salt sensitivity or salt resistance in terms of the development of hypertension. Female salt-sensitive Sabra hypertension-prone (SBH/y) rats were crossed with male salt-resistant Sabra hypertension-resistant (SBN/y) rats, resulting in an F2 cohort consisting of 100 males and 132 females. Systolic blood pressure (BP) was measured in rats at 6 weeks of age under basal conditions and after 4 weeks of salt loading. Genotypes for 24 polymorphic microsatellite markers localized to chromosome 1 and for 8 markers localized to chromosome 17 were determined in F2 and cosegregation with BP was evaluated by ANOVA and multipoint linkage analysis. Basal BP did not cosegregate with any locus on chromosomes 1 or 17. In contrast, BP after salt loading showed significant cosegregation with three QTLs, two on chromosome 1 and one on chromosome 17, designated SS1a, SS1b, and SS17, respectively; the maximal logarithm of the odds (LOD) scores were 4.71, 4.91, and 3.43, respectively. Further analysis revealed sexual dimorphism. In male F2, BP response to salt loading cosegregated with one QTL (LOD score 4.52) and a second QTL (LOD score 2.98), both on chromosome 1 and coinciding with SS1a and SS1b, respectively. In female rats, BP response cosegregated with one QTL on chromosome 1 (LOD score 3.08) coinciding with SS1b, and with a second QTL on chromosome 17 (LOD score 3.66) coinciding with SS17. In males, the additive effects of the two QTLs on chromosome 1 accounted for most of the BP variance to salt loading, whereas in females the additive effects of the QTLs on chromosomes 1 and 17 accounted for over two thirds of the variance. These results identify three putative gene loci on chromosomes 1 and 17 that contribute importantly to salt sensitivity and/or resistance and uncover sex specificity in the role that salt susceptibility genes fulfill in the development of hypertension.
在高血压的Sabra大鼠模型中开展了随机基因组筛查，以寻找在高血压发生发展过程中导致盐敏感性或盐抵抗性的基因。盐敏感的雌性Sabra高血压易感（SBH/y）大鼠与盐抵抗的雄性Sabra高血压抵抗（SBN/y）大鼠杂交，产生了一个由100只雄性和132只雌性组成的F2代群体。在基础条件下以及盐负荷4周后，测量6周龄大鼠的收缩压（BP）。在F2代中确定了位于1号染色体上的24个多态性微卫星标记以及位于17号染色体上的8个标记的基因型，并通过方差分析和多点连锁分析评估与血压的共分离情况。基础血压与1号或17号染色体上的任何位点均无共分离。相反，盐负荷后的血压与三个数量性状位点（QTL）表现出显著共分离，两个在1号染色体上，一个在17号染色体上，分别命名为SS1a、SS1b和SS17；最大优势对数（LOD）分数分别为4.71、4.91和3.43。进一步分析揭示了性别二态性。在雄性F2代中，盐负荷后的血压反应与一个QTL（LOD分数4.52）和第二个QTL（LOD分数2.98）共分离，二者均在1号染色体上，分别与SS1a和SS1b重合。在雌性大鼠中，血压反应与1号染色体上的一个QTL（LOD分数3.08）共分离，该QTL与SS1b重合，还与17号染色体上的第二个QTL（LOD分数3.66）共分离，该QTL与SS17重合。在雄性中，1号染色体上两个QTL的加性效应占盐负荷后血压变异的大部分，而在雌性中，1号和17号染色体上QTL的加性效应占变异的三分之二以上。这些结果确定了1号和17号染色体上三个假定的基因位点，它们对盐敏感性和/或抗性有重要贡献，并揭示了盐敏感性基因在高血压发生发展中所起作用的性别特异性。
