Genetic polymorphisms of L-type calcium channel alpha1C and alpha1D subunit genes are associated with sensitivity to the antihypertensive effects of L-type dihydropyridine calcium-channel blockers.
BACKGROUND
The response of blood pressure (BP) to L-type dihydropyridine calcium-channel blockers (dCCBs) differs among individuals.


RESULTS
A pharmacogenomic analysis was undertaken in 161 patients with essential hypertension who were treated with dCCBs to study whether genetic polymorphisms of the calcium channel alpha1C and alpha1D subunit genes, CACNA1C and CACNA1D, are associated with the antihypertensive effects of dCCBs. Responders were defined as those in whom systolic BP (SBP) was lowered by more than 20 mmHg or diastolic BP (DBP) was lowered by more than 10 mmHg after treatment with dCCBs. Eleven sequence-proven polymorphisms of CACNA1C and 5 common polymorphisms of CACNA1D chosen from a public database were subjected to genotypic analysis. The comparison of polymorphism prevalence between responders and nonresponders showed significant differences in CACNA1D rs312481G>A and rs3774426C>T, and in CACNA1C 527974G>A. There were significant differences in SBP or DBP between alleles in these single nucleotide polymorphisms (SNPs). A much more significant reduction in BP was observed for the combined presence of these SNPs.


CONCLUSIONS
Three SNPs in CACNA1D or CACNA1C are genetic polymorphisms conferring sensitivity to the antihypertensive effects of L-type dCCBs in patients with hypertension. The BP reduction by L-type dCCBs might be predicted by evaluating these polymorphisms.
Kamide
Kei
K
Division of Hypertension and Nephrology, Research Institute, National Cardiovascular Center, Suita, Japan. kamide@hsp.ncvc.go.jp
Yang
Jin
J
Matayoshi
Tetsutaro
T
Takiuchi
Shin
S
Horio
Takeshi
T
Yoshii
Masayoshi
M
Miwa
Yoshikazu
Y
Yasuda
Hisayo
H
Yoshihara
Fumiki
F
Nakamura
Satoko
S
Nakahama
Hajime
H
Miyata
Toshiyuki
T
Kawano
Yuhei
Y
D000368:Aged; D000483:Alleles; D002121:Calcium Channel Blockers / Q000008:administration & dosage*; D020746:Calcium Channels, L-Type / Q000235:genetics*; D004095:Dihydropyridines / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
C079146:CACNA1C protein, human; C472073:CACNA1D protein, human; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D004095:Dihydropyridines; C038806:1,4-dihydropyridine