Quantitative Trait Loci Mapping for Intracellular Calcium in Spontaneously Hypertensive Rats

Increased intracellular calcium ([Ca 2+] i) in platelets is also proposed as an intermediate phenotype for hypertension in spontaneously hypertensive rats (SHR). Increased [Ca 2+] i in platelets is hypothesized to contribute to atherothrombotic events. Platelet hyperactivity is frequently associated with cardiovascular disease. In a genome scan, we performed the quantitative trait loci (QTL) mapping for [Ca 2+] 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 [Ca 2+] i in Ca 2+-free and in Ca 2+-containing buffers was measured in platelets using the Fura-2 method. Among the parental strains, systolic blood pressure and thrombin-stimulated [Ca 2+] i were significantly greater in SHR than in Fischer 344 and F 1 rats. The sarco(endo)plasmic reticulum Ca 2+-dependent ATPase II gene locus ( Serca2) between D12Mgh5 and D12Mgh6 showed the significant linkage for thrombin-stimulated [Ca 2+] i in Ca 2+-free and Ca 2+-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 [Ca 2+] i in Ca 2+-free and in Ca 2+-containing buffers, respectively. The peak logarithm of the odds scores were 2.6 and 2.1, respectively. A significant QTL for [Ca 2+] 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 [Ca 2+] i may contribute to cardiovascular disease via platetet hyperactivity, independent of blood pressure elevation.