CACNA1C polymorphisms are associated with the efficacy of calcium channel blockers in the treatment of hypertension.
Retrospective pharmacogenetic analysis was performed on 120 Caucasian subjects. Subjects were obtained in collaboration with the Estonian Genome Project and Egeen Inc. (CA, USA), who provided blinded medical record and genetic data to the researchers, respectively. Subjects selected from the Estonian Genome Project had a diagnosis of hypertension confirmed by at least two blood pressure measurements and multiple follow-up measurements for assessing calcium channel blocker antihypertensive treatment outcome. Treatment outcome was scored positive if at least three follow-up blood pressure measurements were nonhypertensive and no more than one follow-up measurement was hypertensive (>140/90). The genotypes of 62 single nucleotide polymorphisms (SNPs) in the calcium channel, voltage-dependent, L type, alpha 1C subunit (CACNA1C) gene were obtained for each subject from a blood sample. Univariate analyses with multiple test correction were conducted using family-wise error rate and false discovery rate methods. Three SNPs in CANCA1C had significant associations with antihypertensive outcome, combining to yield a positive treatment outcome of less than 15 to 80%.
Bremer
Troy
T
Prediction Sciences, 9404 Genesee Ave., Suite 210, La Jolla, CA 92037, USA. tbremer@predict.net
Man
Albert
A
Kask
Kalev
K
Diamond
Cornelius
C
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017311:Amlodipine / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000235:genetics*; D015736:Felodipine / Q000627:therapeutic use; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies
D000959:Antihypertensive Agents; C079146:CACNA1C protein, human; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D017311:Amlodipine; D015736:Felodipine