The microsatellite polymorphism of heme oxygenase-1 is associated with baseline plasma IL-6 level but not with restenosis after coronary in-stenting

摘要

Background Vascular smooth muscle cells (VSMCs) can express heme-oxygenase (HO), a rale-limiting enzyme in the degradation of heme to bilirubin, ferritin and carbon monoxide (CO). VSMC-derived CO can suppress VSMC proliferation and may serve as an antiproliferation factor. The promoter region of HO-1 shows a polymorphism with different (GT)_n repeats that has been reported to differently induce gene expression. The objective of this study was to examine the effect of this variation on the occurrence of restenosis after in-stent treatment in patients with coronary artery disease. Methods Candidates who underwent coronary stent implantation were genotyped for the HO-1 promoter polymorphism using polymerase chain reaction (PCR) and automated DNA capillary sequencer. Serum levels of IL-6 and C-reactive protein ( CRP) were obtained at baseline, 24 hours and 48 hours after stenting. The primary end point for the study was angiographic evidence of in-stent restenosis at 6 months. All parameters for evaluation of restenosis were analysed by quantitatve computer-assisted angiographic analysis ( QCA). Results One hundred and eighty-seven patients who underwent coronary stent implantation were studied of whom 27. 8% showed ≥ 50% restenosis after 6 months. The distribution of (GT)_n repeats of all patients in the promoter region of HO-1 genotype ranged from 22 to 42, with (GT)_(25) and (GT)_(32) being the two most common alleles. The allelic repeats were divided into the short class (S) with 29 (GT)_n, the middle class (M) with 30-37 (GT)_n and the long class (L) with 38 (GT)_n. There was no significant difference in the restenosis between the genotype groups or between post operation levels of inflammation markers, but carriers of the S allele (n = 120) had 33. 3% lower baseline IL-6 compared with non-S carriers (n =67, P =0. 0008). Conclusions Although no association was observed between the HO-1 promoter polymorphism and coronary in-stent restenosis following the stent procedure, the association with plasma IL-6 levels suggests that HO-1 S allele might protect from the atherosclerotic inflammatory process.