Lipid metabolism and occurrence of post-percutaneous transluminal coronary angioplasty restenosis: role of cholesteryl ester transfer protein and paraoxonase/arylesterase

Abstract

Summary. Plasma lipid metabolic and transfer processes have recently been suggested to play an important role in the development of early restenosis, a major complication of percutaneous transluminal coronary angioplasty (PTCA); in particular, the common variants of genes for cholesteryl ester transfer protein (CETP) and paraoxonase (PONA) have been implicated. We had the opportunity to investigate this question in a large, prospective cohort characterized by quantitative coronary angiography in all subjects. The CETP-TaqIB (intron 1), CETPMspI (intron 8), and PONA-AlwI (exon 2) polymorphisms were characterized in a cohort of 779 patients of whom 342 ('cases') had developed restenosis (as defined by >50% loss of lumen compared with immediate postprocedure results) at repeat angiography at 6 months post PTCA. Selected frequencies for CETP B1 and B2 alleles (absence/presence of TaqIB site) were 0.65 and 0.35 (cases) and 0.65 and 0.35 (controls), respectively; frequencies for CETP M1 and M2 alleles (absence/presence of MspI site) were 0.20 and 0.80 (cases), 0.21 and 0.79 (controls), respectively; frequencies for PONA A and B alleles (absence/presence of AlwI site) were 0.73 and 0.27 (cases), 0.72 and 0.28 (controls), respectively. All observed genotype frequencies were in Hardy-Weinberg equilibrium. There was no evidence for gene-gene interaction, or an association between genotype and restenosis or degree of lumen loss (adjusted for covariates). Our data, collected in the largest study of its kind so far, indicate that the common variants for CETP and PONA are not associated with incidence of restenosis after PTCA, and are therefore not useful markers for risk assessment.

Lack of Association Between the Cholesteryl Ester Transfer Protein Gene—TaqIB Polymorphism and Coronary Restenosis Following Percutaneous Transluminal Coronary Angioplasty and Stenting: A Pilot Study

“…These results were in agreement with those from the largest cohort of post-PTCA patients (n ¼ 779) studied so far. 19 In that study, no association was found between TaqIB genotype and post-PTCA restenosis, and the result was not affected by the adjustment for age, gender, BMI, total serum cholesterol, smoking status, blood pressure, diabetes mellitus, or family history of myocardial infarction.…”

“…Potential confounding factors previously considered in relation to TaqIB, except for those discussed above, are drug therapy with statins and BMI. 19,31,32 It is not yet known whether statins have any favorable therapeutic effect in coronary restenosis, but pravastatin has been shown to modulate CETP transfer and/or CETP levels. 31,32 It can therefore be difficult to study a possible genetic contribution of TaqIB under the impact of statins.…”

Paraoxonase and arylesterase activities in stent restenosis in bare metal stent

“…This study examined only women patients with balloon angioplasty without including patients with stent [11]. Recently, other studies showed that they found no association between the paraoxonase polymorphism and restenosis after PTCA [12,13].…”

Present status of outcome prediction of invasive coronary treatment by using genetic markers

“…A more recent study did not find an association of the c.388T4C (p.Cys130Arg), c.-1046T4G, or c.-714C4G sequence variations in the APOE gene and the risk of in-stent restenosis. Further candidate genes that were not associated with the risk of restenosis after PTCA include the genes for cholesterol ester transfer protein (CETP, M30185) and HDL-associated paraoxonase (PON1, AF539592) [Zee et al, 2003].…”