title: Inflammatory response to coronary artery bypass surgery: does the heme-oxygenase-1 gene microsatellite polymorphism play a role?
abstract: 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 < 0.0001). 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 22-42, with (GT)25 and (GT)32 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.
authors.affiliation: Cardiovascular Department, Second Affiliated Hospital of Jiangxi Medical College, Nanchang 330006, China. lipingaa66@hotmail.com
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.forename: Jules
authors.initials: J
authors.lastname: Sanders
authors.forename: Emma
authors.initials: E
authors.lastname: Hawe
authors.forename: David
authors.initials: D
authors.lastname: Brull
authors.forename: Hugh
authors.initials: H
authors.lastname: Montgomery
authors.forename: Steve
authors.initials: S
authors.lastname: Humphries
mesh_terms: D000328:Adult; D000368:Aged; D002097:C-Reactive Protein / Q000032:analysis; D001026:Coronary Artery Bypass; D005340:Fibrinogen / Q000032:analysis; D005838:Genotype; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics*; D051547:Heme Oxygenase-1; D006801:Humans; D007249:Inflammation / Q000209:etiology*; D015850:Interleukin-6 / Q000097:blood; D008565:Membrane Proteins; D018895:Microsatellite Repeats; D008875:Middle Aged; D011110:Polymorphism, Genetic
chemical_list: D015850:Interleukin-6; D008565:Membrane Proteins; D005340:Fibrinogen; D002097:C-Reactive Protein; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1