Association of HO-1 (GT)n Promoter Polymorphism and Cardiovascular Disease: A Reanalysis of the Literature.
BACKGROUND
Heme-oxygenase 1 (HO-1), an inducible heme-degrading enzyme, has antiatherogenic effects through its enzymatic end products. HO-1 gene expression is modulated by a guanidine thymidine dinucleotide ([GT]n) repeat polymorphism in the promoter region. Shorter repeats with (GT)n < 25 are associated with higher inducibility and activity of HO-1.


METHODS
We performed a systematic review of all literature from 1997 to 2013 on the association of the HO-1 (GT)n and cardiovascular disease (CVD). On the basis of predefined criteria (patient characteristics, genotype data format, allelic distribution, repeat length cutoff) 41 articles were selected. Patients were redistributed into 4 homogeneous subpopulations: patients with CVD (CVD group), patients without CVD (nonCVD), 'controls' with unknown cardiovascular status (unspecified) and children younger than 20 years of age (unselected). Genotype distributions (homozygous short [SS] or long [LL], and heterozygous) of the 4 patient categories were compared and odds ratios (ORs) for CVD were calculated using logistic regression analysis.


RESULTS
Overall, the proportion of the SS genotype was lower in CVD compared with nonCVD and unspecified. The ORs for CVD was highest in patients carrying the LL genotype (OR LL vs SS, 1.769 [95% confidence interval, 1.594-1.963]). Furthermore, genotype distribution differed between Caucasian and Asian individuals, the latter having a much higher proportion of the SS genotype (22% vs 11%).


CONCLUSIONS
This review of the available literature on the epidemiological association between the HO-1 (GT)n repeat polymorphism and CVD supports the presumed protective effects of HO-1. The second but probably even more relevant finding of our review is that racial disparities in HO-1 (GT)n repeat length distribution exist and might influence the associations of the genotype with CVD status.
Laboratory of Nephrology, Department of Immunology and Microbiology, KU Leuven, Leuven, Belgium; Department of Nephrology, Dialysis and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium.
Kristien E L
KE
Daenen
Department of Nephrology, Dialysis and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium.
Pieter
P
Martens
Laboratory of Nephrology, Department of Immunology and Microbiology, KU Leuven, Leuven, Belgium; Department of Nephrology, Dialysis and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium. Electronic address: bert.bammens@uzleuven.be.
Bert
B
Bammens
D000483:Alleles; D002318:Cardiovascular Diseases / Q000201:enzymology / Q000235:genetics*; D005787:Gene Frequency; D005838:Genotype; D051547:Heme Oxygenase-1 / Q000235:genetics*; D006801:Humans; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic
D051547:Heme Oxygenase-1