- 作者：Yoichi Ohno ; Hiromichi Suzuki ; Hisao Tanase ; Keiichi Otsuka ; Takayuki Sasaki ; Taichi Suzawa ; Toshiyuki Morii ; Yosuke Ando ; Tatsuya Maruyama ; Takao Saruta
- 关键词：Intracellular calcium ; quantitative trait loci ; spontaneously hypertensive rats ; sarco(endo)plasmic reticulum calcium-dependent ATPase II gene ; Sa gene
- 刊名：American Journal of Hypertension
- 出版年：2005
- 出版时间：May 2005
- 年：2005
- 卷：18
- 期：5
- 页码：666-671
- 全文大小：227 K
Background
Increased intracellular calcium ([Ca2+]i) in platelets is also proposed as an intermediate phenotype for hypertension in spontaneously hypertensive rats (SHR). Increased [Ca2+]i in platelets is hypothesized to contribute to atherothrombotic events. Platelet hyperactivity is frequently associated with cardiovascular disease.Methods
In a genome scan, we performed the quantitative trait loci (QTL) mapping for [Ca2+]i in back-crossed rats derived from SHR and normotensive Fischer 344 rats, which demonstrated a single major QTL for hypertension on chromosome 1. Thrombin-stimulated [Ca2+]i in Ca2+-free and in Ca2+-containing buffers was measured in platelets using the Fura-2 method.
Results
Among the parental strains, systolic blood pressure and thrombin-stimulated [Ca2+]i were significantly greater in SHR than in Fischer 344 and F1 rats. The sarco(endo)plasmic reticulum Ca2+-dependent ATPase II gene locus (Serca2) between D12Mgh5 and D12Mgh6 showed the significant linkage for thrombin-stimulated [Ca2+]i in Ca2+-free and Ca2+-containing buffers. The peak logarithm of the odds scores were 3.6 and 3.3, respectively. These QTL explained 19.8 % and 17.4 % of the total variances, respectively. D3Mit13 and DXMgh1 showed suggestive linkage for thrombin-stimulated [Ca2+]i in Ca2+-free and in Ca2+-containing buffers, respectively. The peak logarithm of the odds scores were 2.6 and 2.1, respectively.
Conclusions
A significant QTL for [Ca2+]i was mapped near Serca2 on chromosome 12, and suggestive QTL were identified near D3Mit13 and DXMgh1 in a genome scan. Genetic abnormalites in platelet [Ca2+]i may contribute to cardiovascular disease via platetet hyperactivity, independent of blood pressure elevation.