Table 1.

Summary of the Literature on HO-1 VNTR Polymorphism and Cardiovascular Disease End Points in Humans

ReferencePrimary End Pointn (Cases)Years of FUSample CompositionVNTR Cut-Off(s) (≥)Result*Effect (Short Allele)Effect (Long Allele)
Exner 200115Restenosis after femoropopliteal BA96 (23)0.5Caucasian, PAD25 and 29p(D) OR 0.2 (0.06, 0.70)
Chen 200211CAD796 (474)CCAsian, CAG23 and 32p(D) OR 4.7 (1.9, 12.0) in diabetics
Kaneda 200216CAD577 (298)CSAsian, CAG27p(E) S/S vs L/L: OR 0.23 (0.07, 0.72) in subjects with high cholesterol; OR 0.23 (0.08, 0.71) in diabetics; OR 0.40 (0.17, 0.95) in smokers
Schillinger 200217AAA, CAD, PAD271 (210)CCCaucasian, vascular risk patients25p(R) more L/L genotype in AAA, P=0.04 NS for CAD, PAD
Chen 200318Restenosis after coronary stenting, ACE323 (111)0.5Asian, CAD26p(D) OR 3.74 (1.61, 8.70) for stenting (D) OR 3.26 (1.58, 6.72) for ACE
Endler 200419CAD, MI649 (438)CCCaucasian, vascular risk patients25n(D) P=0.94
Funk 200420Ischemic stroke or TIA797 (399)CCCaucasian, stroke25p(E) S/S vs L/L: OR 0.2 (0.1,0.6)
Schillinger 200421Restenosis after femoropopliteal BA381 (95)0.5Caucasian, PAD25p(R) RR 2.33 (1.41, 4.17), NS for stenting
Dick 200522MI or PCI or CABG472 (133)1.75 (M)Caucasian, PAD25p(R) HR 2.17 (1.15, 4.17), NS for MACE, all-cause mortality, cerebrovascular events
Gulesserian 200523Restenosis after coronary stenting199 (102)0.5–0.75Caucasian, CAD30p(D) OR 1.9 (1.0, 3.4), stronger effect in smokers
Li 200524Restenosis after coronary stenting187 (52)0.5Asian, CAD30 and 38n(D) 30.8% restenosis in S carriers, 22.4% in others; P=0.22
Wijpkema 200625Restenosis after coronary angioplasty3146 (287)0.8 (M)Caucasian, CAD25nS/L vs. S/S: HR 1.14 (0.90, 1.45); L/L vs. S/S: HR 0.87 (0.55, 1.38)
Tiroch 200726Restenosis after coronary stenting1357 (401)0.5Caucasian, CAD25nrestenosis in 29.2% (S/S), 29.5% (S/L), 29.6% (L/L); P=0.99
Chen 200827CAD986 (664)CSAsian, CAG27p(R) OR 2.81 (1.22, 6.47) in diabetics; NS with adjustment for ferritin and bilirubin
Lüblinghoff 200928CAD3219 (2526)§7.8 (M)Caucasian, CAG26 or 28nS/L vs. S/S: OR 0.70 (0.49, 1.01); L/L vs. S/S: OR 0.71 (0.49, 1.02)
Bai 201029Ischemic stroke347 (183)CCAsian, stroke patients and hospital controls27p(M) OR 2.07 (1.07–4.01) in subjects with low HDL
Wu 201030CVD mortality504 (22)10.7 (M)Asian, arsenic exposure27p(R) OR 2.63 (1.11, 6.25)
Chen 201213CAD4596 (2298)CCAsian, general population26p(E) S/S vs L/L: OR 0.60 (0.44, 0.81) in subjects with high oxidative stress
Chen 201331CVD1080 (307)4.2 (M)Asian, hemodialysis27p(R) HR 1.62 (1.28, 2.04)
Gregorek 201332AAA234 (117)CCCaucasian, AAA patients and hospital controls25nS/L vs. L/L: OR 1.53 (0.90, 3.09); S/S vs. L/L: OR 1.24 (0.87, 1.96)
  • AAA indicates abdominal aortic aneurysm; ACE, adverse coronary events; BA, balloon angioplasty; CABG, coronary artery bypass grafting; CAD, coronary artery disease; CAG, coronary angiography; CC, case-control study; CS, cross-sectional study; CVD, cardiovascular disease; FU, follow-up; HDL, high-density lipoprotein cholesterol; HO-1, heme oxygenase-1; HR, hazard ratio; (M), median follow-up in years; MACE, major adverse cardiovascular events; MI, myocardial infarction; NS, not statistically significant; OR, odds ratio; PAD, peripheral arterial disease; PCI, percutaneous coronary intervention; RR, risk ratio; TIA, transient ischemic attack; and VNTR, variable number tandem repeat.

  • * p, positive study—found significant association of HO-1 VNTR length with primary end point; n, negative study—did not find significant association of HO-1 VNTR length with primary end point.

  • (D), dominant effect, ie, applies to allele carriers (eg, pooled S/S and S/L vs L/L); (E), extreme group comparison (eg, S/S vs L/L); (R), recessive effect, ie, applies to those homozygous for the respective allele (eg, S/S vs pooled S/L and L/L); (M), 1 study applied the cut-off to average within-subject allele length, forming L and S genotypes.

  • 258 MCI and 180 stable CAD.

  • § 2526 CAD and 1339 MI; 752 death.