Mashimo T, Nabika T, Matsumoto C, Tamada T, Ueno K, Sawamura M, Ikeda K, Kato N, Nara Y, Yamori Y
Department of Life Science, Graduate School of Human and Environmental Studies, Kyoto University, Japan.
Am J Hypertens. 1999 Nov;12(11 Pt 1):1098-104. doi: 10.1016/s0895-7061(99)00084-9.
To evaluate the effects of nongenetic factors, aging, and salt-loading on the quantitative trait loci (QTLs) for blood pressure (BP), we conducted a genome-wide linkage analysis using multiple sets of BP measurements in 125 male F2 generation cross derived from stroke-prone spontaneously hypertensive rats and normotensive Wistar-Kyoto rats. The experiment was arranged in two stages. In the first stage, corresponding to the developing period of the rats, BP was measured repeatedly without loading of salt; this continued until the rats were 5 months of age. In the second stage, after the baseline BP leveled off, 1% salt water was given to the rats and BP was monitored for the subsequent 7 months. Genome scanning was performed using 201 markers. In the developing period, three QTLs were identified on chromosomes 1, 3, and 4 (logarithmic odds [LOD] scores of 5.6, 3.1, and 3.2, respectively), which had peaks at 8 or 10 weeks of age. In the latter salt-loading stage, QTLs for BP were detected on chromosomes 1 and 10 (LOD scores 4.6 and 4.5, respectively). When the BP increase during salt-loading was analyzed as a phenotype, however, only the region on chromosome 10 showed linkage at a suggestive level (LOD score 3.2). The present study provides experimental evidence that QTLs for BP could be modulated by nongenetic factors, such as aging and salt-loading.
为了评估非遗传因素、衰老和盐负荷对血压（BP）数量性状基因座（QTL）的影响，我们使用了来自易中风自发性高血压大鼠和正常血压Wistar-Kyoto大鼠的125只雄性F2代杂交大鼠的多组血压测量值进行了全基因组连锁分析。实验分两个阶段进行。在第一阶段，对应于大鼠的发育期，在不给予盐负荷的情况下反复测量血压；这种情况持续到大鼠5个月大。在第二阶段，在基线血压趋于平稳后，给大鼠饮用1%的盐水，并在随后的7个月内监测血压。使用201个标记进行基因组扫描。在发育期，在1号、3号和4号染色体上鉴定出三个QTL（对数优势[LOD]分数分别为5.6、3.1和3.2），其峰值出现在8周或10周龄。在随后的盐负荷阶段，在1号和10号染色体上检测到了BP的QTL（LOD分数分别为4.6和4.5）。然而，当将盐负荷期间的血压升高作为一种表型进行分析时，只有10号染色体上的区域显示出提示性水平的连锁（LOD分数为3.2）。本研究提供了实验证据，表明血压的QTL可能受到衰老和盐负荷等非遗传因素的调节。
