Independent genetic susceptibility to cardiac hypertrophy in inherited hypertension
Independent genetic susceptibility to cardiac hypertrophy in inherited hypertension
复制标题
DOI：
10.1161/01.hyp.31.3.741
复制
发表时间：
1998-03-01
期刊：
影响因子：
8.3
通讯作者：
Harrap, SB
中科院分区：
文献类型：
--
作者：
Innes, BA;McLaughlin, MG;Harrap, SB
心脏肥大是高血压常见但并非不可避免的并发症。高血压患者心脏大小的变化可能反映了心脏肥大的独立遗传易感性。使用实验遗传模型，我们确定了数量性状基因座的位置负责心脏肥大和/或高血压。我们研究了182只来自自发性高血压大鼠和血压正常的Donryu大鼠杂交的F-2雄性动物。在20周龄时测量直接平均动脉压（MAP）和左心室（LV）mas，并获得DNA进行连锁分析。MAP的估计遗传率为62%，每单位体重表示的LV质量（相对LV质量）的估计遗传率为76%。我们使用了185个多态性标记，平均标记间距离为12.3厘摩的全基因组扫描在一个代表性的亚组的46只动物，以确定初步的数量性状基因座，然后映射在所有182只雄性F-2大鼠。两个位点显示比值分数的对数>4.0。2号染色体上的一个，Lvm-1，与相对LV质量相关，但没有证据表明与MAP相关。1号染色体上的另一个位点，MAP-1，与MAP连锁。在同一区域，一个位点Lvm-2与相对LV质量。这些数据表明，在自发性高血压大鼠的2号染色体上存在一个遗传位点，该位点独立于血压影响相对LV质量。
Cardiac hypertrophy is a common but not inevitable complication of hypertension. Variation in heart size in hypertensives may reflect independent genetic susceptibility to cardiac hypertrophy. Using an experimental genetic model, we determined the location of quantitative trait loci responsible for cardiac hypertrophy and/or hypertension. We studied 182 F-2 male animals derived from a cross of the spontaneously hypertensive rat and normotensive Donryu rats. Direct mean arterial pressure (MAP) and left ventricular (LV) mas were measured at 20 weeks of age, and DNA was obtained for linkage analysis. The estimated heritability of MAP was 62% and for LV mass expressed per unit of body weight (relative LV mass) was 76%. We used 185 polymorphic markers, with an average intermarker distance of 12.3 centimorgans for a genome-wide scan in a representative subgroup of 46 animals to identify preliminary quantitative 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 chromosome 2, Lvm-1, was linked to relative LV mass but showed no evidence of linkage 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 of the spontaneously hypertensive rat that affects relative LV mass independently of blood pressure.