title: Interleukin-1B genotype modulates the improvement of coronary artery reactivity by lipid-lowering therapy with pravastatin: a placebo-controlled positron emission tomography study in young healthy men.
abstract: A polymorphism at position -511 of interleukin-1B (IL-1B) gene promoter regulates IL-1B levels, immune and inflammatory responses and possible atherogenesis. We used positron emission tomography (PET) to study whether coronary reactivity or its response to pravastatin is related to this IL-1B polymorphism. The study comprised a randomized, double-blind, placebo-controlled trial with two treatment groups: (i) pravastatin (40 mg/day, n=14) and (ii) placebo (n=20) for 6 months (baseline mean cholesterol 5.5 +/- 0.8 mmol/l; age 35 +/- 4 years). Myocardial blood flow was measured by PET at rest and during adenosine infusion using 15O-labelled water. PET studies, lipid, IL-1beta and C-reactive protein analyses were performed at baseline and after 6 months of therapy. IL-1B genotype was determined by polymerase chain reaction. There were no differences between IL-1B allele 2 carriers (A2+) and non-carriers (A2-) in basal or adenosine-stimulated myocardial flow (ASMF), at baseline. Regarding the change in ASMF and coronary flow reserve, there was a significant IL-1B genotype-by-treatment group interaction (analysis of covariance, P=0.028 and P=0.002, respectively) during follow-up. In the pravastatin group, the ASMF increased by 18.0% in subjects with IL-1B A2- (n=7), but decreased by 2% in subjects with IL-1B A2+ (n=7). There were no significant changes from the baseline values in placebo recipients. After treatment, both genotype groups showed a similar decrease in serum total and low density lipoprotein cholesterol (P<0.0001 for both). In conclusion, coronary function improves after 6 months of pravastatin therapy in subjects with the IL-1B A2- allele but not in those with the IL-1B A2+ allele.
mesh_terms: D000241:Adenosine / Q000008:administration & dosage; D000328:Adult; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D002097:C-Reactive Protein / Q000378:metabolism; D008078:Cholesterol, LDL / Q000378:metabolism; D003326:Coronary Circulation / Q000187:drug effects*; D004311:Double-Blind Method; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics*; D050356:Lipid Metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D010919:Placebos; D011110:Polymorphism, Genetic; D017035:Pravastatin / Q000494:pharmacology*; D014055:Tomography, Emission-Computed
chemical_list: D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D007375:Interleukin-1; D010919:Placebos; D002097:C-Reactive Protein; D000241:Adenosine; D017035:Pravastatin