Rubattu S, Volpe M, Kreutz R, Ganten U, Ganten D, Lindpaintner K
Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Nat Genet. 1996 Aug;13(4):429-34. doi: 10.1038/ng0896-429.
Stroke is a complex disorder with a poorly understood multifactorial and polygenic aetiology. We used the stroke-prone spontaneously hypertensive rat (SHRSP) as a model organism, mated it with the stroke-resistant spontaneously hypertensive rat (SHR) and performed a genome-wide screen in the resultant F2 cohort where latency until stroke, but not hypertension (a major confounder) segregated. We identified three major quantitative trait loci, STR1-3, with lod scores of 7.4, 4.7 and 3.0, respectively, that account for 28% of the overall phenotypic variance. STR2 colocalizes with the genes encoding atrial and brain natriuretic factor, peptides with important vasoactive properties. Our results demonstrate the existence of primary, blood pressure-independent genetic factors predisposing to a complex form of stroke.
中风是一种复杂的疾病，其多因素和多基因病因尚不清楚。我们使用易中风自发性高血压大鼠（SHRSP）作为模式生物，将其与抗中风自发性高血压大鼠（SHR）交配，并在所得的F2队列中进行全基因组筛选，其中直到中风的潜伏期（而非高血压，高血压是一个主要混杂因素）发生了分离。我们确定了三个主要的数量性状基因座，即STR1 - 3，其对数优势分数分别为7.4、4.7和3.0，它们占总体表型变异的28%。STR2与编码心房利钠因子和脑利钠因子的基因共定位，这些肽具有重要的血管活性特性。我们的结果证明存在原发性、与血压无关的遗传因素，这些因素易导致一种复杂形式的中风。
