Quantitative trait loci mapping for intracellular calcium in spontaneously hypertensive rats.
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 platelet hyperactivity, independent of blood pressure elevation.
Ohno
Yoichi
Y
Department of Internal Medicine, Green Town Clinic Center, Saitama, Japan. yo1-ohno@cb3.so-net.ne.jp
Suzuki
Hiromichi
H
Tanase
Hisao
H
Otsuka
Keiichi
K
Sasaki
Takayuki
T
Suzawa
Taichi
T
Morii
Toshiyuki
T
Ando
Yosuke
Y
Maruyama
Tatsuya
T
Saruta
Takao
T
D000818:Animals; D001792:Blood Platelets / Q000378:metabolism; D001794:Blood Pressure; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000235:genetics; D005260:Female; D006973:Hypertension / Q000235:genetics* / Q000378:metabolism; D008297:Male; D040641:Quantitative Trait Loci; D051381:Rats; D011916:Rats, Inbred F344; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases
C506948:Atp2a2 protein, rat; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases; D002118:Calcium