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


CONCLUSIONS
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.
Lüblinghoff
Nicola
N
Department of Otorhinolaryngology-Head and Neck Surgery, University Medical Center Freiburg, Freiburg, Germany. lueblinghoff@hno.ukl.uni-freiburg.de
Winkler
Karl
K
Winkelmann
Bernhard R
BR
Seelhorst
Ursula
U
Wellnitz
Britta
B
Boehm
Bernhard O
BO
März
Winfried
W
Hoffmann
Michael M
MM
D000328:Adult; D000368:Aged; D003324:Coronary Artery Disease / Q000201:enzymology / Q000235:genetics*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D051547:Heme Oxygenase-1 / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000201:enzymology / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012307:Risk Factors
C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1