Identification of QTLs for various lipid phenotypes In the stroke-prone spontaneously hypertensive rats and their relation to the susceptibility to cerebral stroke

卒中易感自发性高血压大鼠（SHRSP）是已知的脑中风发病率非常高。此外，与正常血压对照组Wistar-Kyoto大鼠（WKY）相比，该品系在脂质代谢方面存在异常。人类流行病学研究表明脂质代谢与脑卒中易感性密切相关，脂质代谢异常可能是SHRSP脑卒中易感性的重要因素之一。因此，在本研究中，我们对SHRSP和WKY之间获得的F2大鼠脂质代谢相关性状进行了遗传分析。我们发现：(1)在染色体3、5、7、15和16上发现了血清胆固醇水平的数量性状位点（QTL），(2)在染色体8和16上发现了血清甘油三酯水平的数量性状位点（QTL），(3)在一些染色体区域观察到雄性和雌性大鼠之间不同的QTL。在5号染色体上，先前的一项研究表明，一个基因对脑中风的易感性负责。该易感位点与血清胆固醇QTL是否在同一区域是一个值得关注的问题。我们现在正在构建这些qtl的同源菌株，以确认这些染色体区域对脂质代谢或脑卒中的影响。

The stroke-prone spontaneously hypertensive rats (SHRSP) are known to have very high incidence of cerebral stroke. In addition, this strain has been known to have an abnormality in the lipid metabolism when compared with the normotensive control, Wistar-Kyoto rats (WKY). As epidemiological studies in humans indicated that the lipid metabolism had a close relation to the susceptibility to cerebral stroke, the abnormal lipid metabolism might be one of the essential factors responsible for the stroke susceptibility in SHRSP. In this study, we therefore performed genetic analyses on the traits related to the lipid metabolism in F2 rats obtained between SHRSP and WKY. We found (1) quantitative trait loci (QTLs) for the serum cholesterol level on chromosomes 3, 5, 7, 15, and 16, (2) a QTL for the serum triglyceride level on chromosome 8, and 16, (3) QTLs different between male and female rats observed in several chromosomal regions. On the chromosome 5, a previous study suggested a gene responsible for the susceptibility to the cerebral stroke. It is of interest whether this susceptibility locus and the QTL for the serum cholesterol are in the same region or not. We are now constructing congenic strains for these QTLs to confirm the effects of these chromosomal regions either on the lipid metabolism or on cerebral stroke.