BackgroundThe
proprotein convertase subtilisin/kexin type 9 (PCSK9) has a key
role in the
regulation of
plasma low-density lipoprotein (LDL)
cholesterol by enhancing the degradation of
LDL receptor. Functional variants in PCSK9 have been associated with differences in
plasma lipids and may contribute to the variability of the response to
cholesterol-lowering
drugs.ObjectiveTo investigate the influence of PCSK9 variants on
plasma lipid profile and response to
atorvastatin in Brazilian subjects.MethodsPCSK9 E670G, I474V, and R46L
single nucleotide polymorphisms (
SNPs) and
plasma lipids were evaluated in 163 hypercholesterolemics (HC) and 171 normolipidemics (NL). HC
patients with indication for
cholesterol-lowering
drug therapy (n = 128) were treated with
atorvastatin (10 mg/d/4 wk). PCSK9
SNPs were analyzed by
real time polymerase chain reaction.ResultsFrequencies of the PCSK9
SNPs were
similar between the HC and NL groups.
Logistic regression analysis showed a trend of
association between PCSK9 E670G and
hypercholesterolemia after
adjustment for covariates (P = .059). The 670G
allele was associated with high basal levels of
LDL cholesterol (P = .03) in HC
patients using the extreme discordant
phenotype method. No
association tests were performed for R46L variant because of its very low frequency, whereas the I474V polymorphism and PCSK9
haplotypes were not related to
hypercholesterolemia or variability on
plasma lipids in both NL and HC groups (P > .05).
LDL cholesterol reduction in response to
atorvastatin was not influenced by PCSK9
genotypes or
haplotypes.