Inflammatory response to coronary artery bypass surgery: does the heme-oxygenase-1 gene microsatellite polymorphism play a role?
Li, P.; Sanders, J.; Hawe, E.; Brull, D.; Montgomery, H.; Humphries, S.
Chinese Medical Journal 118(15): 1285-1290
2005
ISSN/ISBN: 0366-6999 PMID: 16117883 Document Number: 592858
Background Heme-oxygenase 1 (HO-1) is a rate-limiting enzyme in the degradation of heme to bilirubin, ferritin and carbon monoxide (CO) and may have significant anti-inflammatory function. The HO-1 gene promoter region shows microsatellite polymorphism with different ( GT) n repeats, reported to differently induce gene expression, with the short allele associated with higher gene expression. We measured the acute inflammatory response using coronary artery bypass surgery ( CABG) as a well-characterized and uniform stimulus and examined the correlation between levels of IL-6, C-reactive protein (CRP) and fibrinogen and their relationship to HO-1 genotype.Methods Two hundred and seventy-five consecutive patients undergoing CABG were genotyped for the HO-1 promoter polymorphism using PCR and automated DNA capillary sequencer. IL-6, CRP and fibrinogen were measured at baseline and 6, 24, 48, 72, 96 and 120 hours after CABG.Results Complete IL-6, CRP and fibrinogen measures were available in 220 patients. Before surgery IL-6 levels showed a strong correlation with CRP and fibrinogen ( r = 0.48, P < 0.0001; r = 0.41, P < 0.0001 respectively), with a significant correlation between CRP and fibrinogen ( r = 0.61, P < 0.0601 All three acute phase reactants showed a significant increase after CABG. After surgery, peak IL-6 was strongly correlated with peak CRP (r =0.34, P = 0.0009) but not with peak fibrinogen (r = 0.15, P = 0.13), while peak CRP and peak fibrinogen were significantly correlated ( r = 0.415, P < 0.0001). HO-1 allelic repeats ranged from 2242, with (GT)25 and (GT),, being the two most common alleles, and subsequently divided into three groups according to previous published work: < 30 ( GT) n were designated as S ( short), 30 - 37 ( GT) n as M (middle) and long repeats with > 37 ( GT) n as L (long); allele frequency 0.35, 0.58 and 0.07 respectively. Baseline CRP differed by genotype: those carrying at least one long allele having higher CRP than those with no long allele (3.76 0.79 vs. 2.07 0.17, P =0.013). Conversely, those carrying at least one short allele had higher fibrinogen levels than those with no short allele (3.83 +/- 0.79 vs. 3.51 +/- 0.88, P =0.006).Conclusions There is a strong correlation between the measured acute phase reactants both at baseline and after the inflammatory response to CABG in patients with coronary disease. There was an association between the HO-1 microsatellite polymorphism and CRP and fibrinogen levels at baseline but there was no similar association following CABG. This may indicate that HO-1 is associated with chronic atherosclerotic inflammatory processes rather than acute.