Effect of heme oxygenase-1 polymorphisms on lung function and gene expression

• Main Authors: Abboud Raja T (Author), Anthonisen Nicholas R (Author), Connett John E (Author), Shumansky Karey (Author), He Jian-Qing (Author), Akhabir Loubna (Author), Aminuddin Farzian (Author), Tanaka Goh (Author), Paré Peter D (Author), Sandford Andrew J (Author)
• Format: Book
• Published: BMC, 2011-09-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.1186/1471-2350-12-117; 1471-2350
• Keywords: Heme oxygenase; polymorphism; chronic obstructive pulmonary disease; Internal medicine; RC31-1245; Genetics; QH426-470
• Source: BMC Medical Genetics, Vol 12, Iss 1, p 117 (2011)

<p>Abstract</p> <p>Background</p> <p>Oxidative stress induced by smoking is considered to be important in the pathogenesis of Chronic Obstructive Pulmonary Disease (COPD). Heme oxygenase-1 (HMOX1) is an essential enzyme in heme catabolism that is induced by oxidative stress and may play a protective role as an antioxidant in the lung. We determined whether <it>HMOX1 </it>polymorphisms were associated with lung function in COPD patients and whether the variants had functional effects.</p> <p>Methods</p> <p>We genotyped five single nucleotide polymorphisms (SNPs) in the <it>HMOX1 </it>gene in Caucasians who had the fastest (n = 278) and the slowest (n = 304) decline of FEV₁% predicted, selected from smokers in the NHLBI Lung Health Study. These SNPs were also studied in Caucasians with the lowest (n = 535) or the highest (n = 533) baseline lung function. Reporter genes were constructed containing three <it>HMOX1 </it>promoter polymorphisms and the effect of these polymorphisms on H₂O₂and hemin-stimulated gene expression was determined. The effect of the <it>HMOX1 </it>rs2071749 SNP on gene expression in alveolar macrophages was investigated.</p> <p>Results</p> <p>We found a nominal association (p = 0.015) between one intronic <it>HMOX1 </it>SNP (rs2071749) and lung function decline but this did not survive correction for multiple comparisons. This SNP was in perfect linkage disequilibrium with rs3761439, located in the promoter of <it>HMOX1</it>. We tested rs3761439 and two other putatively functional polymorphisms (rs2071746 and the (GT)_npolymorphism) in reporter gene assays but no significant effects on gene expression were found. There was also no effect of rs2071749 on <it>HMOX1 </it>gene expression in alveolar macrophages.</p> <p>Conclusions</p> <p>We found no association of the five <it>HMOX1 </it>tag SNPs with lung function decline and no evidence that the three promoter polymorphisms affected the regulation of the <it>HMOX1 </it>gene.</p>