Impact of apolipoprotein A5 variants on statin treatment efficacy.
OBJECTIVE
Despite the fact that statin treatment efficacy is very high, there are substantial differences in treatment effectiveness among individuals. It is supposed that genetic predisposition plays an important role in these differences, but the contribution of individual polymorphisms is poorly understood. So far, more than 30 genes have been examined with ambiguous results. Apolipoprotein A5 is an important determinant of plasma lipid concentrations and its genetic variation could account for some of the observed differences in the response to statin therapy. However, this has not been analyzed before.


METHODS
We examined the putative association between APOA5 SNPs (c.-1131T>C, c.56C>G and c.457G>A) and efficacy during 3 months of statin treatment in 187 adult Caucasians. Patients were treated with low-dose (10 or 20 mg per day) simvastatin (46.3%), atorvastatin (40.5%) and lovastatin (13.2%).


RESULTS
The decrease in cholesterol was not significantly associated with the type or dose of statin. Carriers of the APOA5 genotype TT-1131 (n = 154) benefited more from statin treatment when compared with the C-1131 allele carriers (n = 33) (Delta low-density lipoprotein cholesterol: -36.3 +/- 15.1% vs Delta low-density lipoprotein cholesterol: -29.9 +/- 12.5%; p < 0.005, Mann-Whitney test). This result was independent of sex, age, BMI and APOE polymorphism.


CONCLUSIONS
Our results suggest that the APOA5 gene variants may play an important role in the pharmacogenetics of statin treatment.
Hubacek
Jaroslav A
JA
Cardiovascular Research Centre, IKEM-DEM-LMG, Videnska 1958/9, 140 21, Prague 4, Czech Republic. jahb@ikem.cz
Adamkova
Vera
V
Prusikova
Martina
M
Snejdrlova
Michaela
M
Hirschfeldova
Katerina
K
Lanska
Vera
V
Ceska
Richard
R
Vrablik
Michal
M
D000328:Adult; D000368:Aged; D000483:Alleles; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A / Q000097:blood / Q000235:genetics*; D016022:Case-Control Studies; D008078:Cholesterol, LDL / Q000097:blood; D015331:Cohort Studies; D018153:Czech Republic; D050171:Dyslipidemias / Q000097:blood / Q000188:drug therapy*; D005260:Female; D005544:Forecasting; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood; D044465:White People / Q000235:genetics / Q000706:statistics & numerical data
C437704:APOA5 protein, human; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014280:Triglycerides