title: 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.
abstract: 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.
authors.affiliation: Division of Hypertension and Nephrology, Research Institute, National Cardiovascular Center, Suita, Japan. kamide@hsp.ncvc.go.jp
authors.forename: Kei
authors.initials: K
authors.lastname: Kamide
authors.forename: Jin
authors.initials: J
authors.lastname: Yang
authors.forename: Tetsutaro
authors.initials: T
authors.lastname: Matayoshi
authors.forename: Shin
authors.initials: S
authors.lastname: Takiuchi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Horio
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Yoshii
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Miwa
authors.forename: Hisayo
authors.initials: H
authors.lastname: Yasuda
authors.forename: Fumiki
authors.initials: F
authors.lastname: Yoshihara
authors.forename: Satoko
authors.initials: S
authors.lastname: Nakamura
authors.forename: Hajime
authors.initials: H
authors.lastname: Nakahama
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Miyata
authors.forename: Yuhei
authors.initials: Y
authors.lastname: Kawano
mesh_terms: 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
chemical_list: C079146:CACNA1C protein, human; C472073:CACNA1D protein, human; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D004095:Dihydropyridines; C038806:1,4-dihydropyridine