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Open Access Research article

Genetic variants of the promoter of the heme oxygenase-1 gene and their influence on cardiovascular disease (The Ludwigshafen Risk and Cardiovascular Health Study)

Nicola Lüblinghoff1, Karl Winkler2, Bernhard R Winkelmann3, Ursula Seelhorst4, Britta Wellnitz4, Bernhard O Boehm5, Winfried März67 and Michael M Hoffmann2*

Author Affiliations

1 Department of Otorhinolaryngology – Head and Neck Surgery, University Medical Center Freiburg, Freiburg, Germany

2 Division of Clinical Chemistry, Department of Medicine, University Medical Center Freiburg, Freiburg, Germany

3 Cardiology Group, Frankfurt-Sachsenhausen, Germany

4 LURIC Study nonprofit LLC, Freiburg, Germany

5 Division of Endocrinology and Diabetes, Department of Medicine, Ulm University, Ulm, Germany

6 Synlab Center of Laboratory Diagnostics, Heidelberg, Germany

7 Institute of Public Health, Medical Faculty of Mannheim, University of Heidelberg, Heidelberg, Germany

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BMC Medical Genetics 2009, 10:36  doi:10.1186/1471-2350-10-36

Published: 23 April 2009

Abstract

Background

Heme oxygenase-1 is an inducible cytoprotective enzyme which handles oxidative stress by generating anti-oxidant bilirubin and vasodilating carbon monoxide. A (GT)n dinucleotide repeat and a -413A>T single nucleotide polymorphism have been reported in the promoter region of HMOX1 to both influence the occurrence of coronary artery disease and myocardial infarction. We sought to validate these observations in persons scheduled for coronary angiography.

Methods

We included 3219 subjects in the current analysis, 2526 with CAD including a subgroup of CAD and MI (n = 1339) and 693 controls. Coronary status was determined by coronary angiography. Risk factors and biochemical parameters (bilirubin, iron, LDL-C, HDL-C, and triglycerides) were determined by standard procedures. The dinucleotide repeat was analysed by PCR and subsequent sizing by capillary electrophoresis, the -413A>T polymorphism by PCR and RFLP.

Results

In the LURIC study the allele frequency for the -413A>T polymorphism is A = 0,589 and T = 0,411. The (GT)n repeats spread between 14 and 39 repeats with 22 (19.9%) and 29 (47.1%) as the two most common alleles. We found neither an association of the genotypes or allelic frequencies with any of the biochemical parameters nor with CAD or previous MI.

Conclusion

Although an association of these polymorphisms with the appearance of CAD and MI have been published before, our results strongly argue against a relevant role of the (GT)n repeat or the -413A>T SNP in the HMOX1 promoter in CAD or MI.