Apo A-I promoter polymorphism influences basal HDL-cholesterol and its response to pravastatin therapy.
Statins decrease cardiovascular morbidity and mortality, essentially, by reducing LDL-cholesterol levels and, additionally, by increasing HDL-cholesterol concentrations. Environmental and genetic factors are known to affect LDL-C response to statins but less is known regarding HDL-C. We have evaluated the lipid and lipoprotein response to 20 mg/day of pravastatin for 16 weeks in relation to the G/A polymorphism in the promoter region of the apo A-I gene in 397 hypercholesterolaemic subjects followed-up on an out-patient basis. In the study population, 61.7% were homozygous for the G allele and 36% were heterozygous. The A allele carriers had an HDL-C 6.5% higher than the G allele homozygotes (P=0.021 in univariate analysis; P=0.009 in multivariate analysis). However, on segregation by gender and smoking status the effect was significant only in non-smoking males. The A allele carriers did not increase their HDL-C concentrations after treatment (-0.3, 95%CI -3.3 to 2.7%) while G allele homozygotes had a 4.9% increase (95%CI 2.5-7.3%). Differences in the response between both groups were significant before (P=0.008) and after adjustment for confounding variables such as age and baseline HDL-C concentration (P=0.046). We conclude that the G/A polymorphism of the apo A-I promoter region affects not only baseline HDL-C concentrations but also its response to pravastatin treatment.
Lahoz
Carlos
C
Unidad de Arteriosclerosis, Hospital Carlos III, C/Sinesio Delgado 10, 28029 Madrid, Spain. clahoz@hciii.insalud.es
Peña
Rocío
R
Mostaza
Jose M
JM
Jiménez
Javier
J
Subirats
Enric
E
Pintó
Xavier
X
Taboada
Manuel
M
López-Pastor
Angela
A
D000483:Alleles; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D016632:Apolipoprotein A-I / Q000235:genetics*; D008076:Cholesterol, HDL / Q000097:blood*; D005260:Female; D006579:Heterozygote; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood* / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration; D011110:Polymorphism, Genetic; D017035:Pravastatin / Q000627:therapeutic use*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011446:Prospective Studies
D000924:Anticholesteremic Agents; D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; D017035:Pravastatin