The microsatellite polymorphism of heme oxygenase-1 is associated with baseline plasma IL-6 level but not with restenosis after coronary in-stenting.
BACKGROUND
Vascular smooth muscle cells (VSMCs) can express heme-oxygenase (HO), a rate-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 quantitative computer-assisted angiographic analysis (QCA).


RESULTS
One hundred and eighty-seven patients who underwent coronary stent implantation were studied of whom 27.8% showed > or = 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.
Li
Ping
P
Cardiovascular Department, Second Affiliated Hospital of Jiangxi Medical College, Nanchang 330006, China. lipingaa66@hotmail.com
Elrayess
Mohamed A
MA
Gomma
Abuzeid H
AH
Palmen
Jutta
J
Hawe
Emma
E
Fox
Kim M
KM
Humphries
Steve E
SE
D000328:Adult; D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D002097:C-Reactive Protein / Q000032:analysis; D023903:Coronary Restenosis / Q000097:blood / Q000201:enzymology / Q000235:genetics*; D005260:Female; D005838:Genotype; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics*; D051547:Heme Oxygenase-1; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D008565:Membrane Proteins; D018895:Microsatellite Repeats; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D015607:Stents
D015850:Interleukin-6; D008565:Membrane Proteins; D002097:C-Reactive Protein; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1