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

BMC Medical Genetics

Andrew J Sandford⁴  Peter D Paré⁴  Raja T Abboud¹  Nicholas R Anthonisen²  John E Connett³  Karey Shumansky⁴  Jian-Qing He⁴  Loubna Akhabir⁴  Farzian Aminuddin⁴  Goh Tanaka⁴ 

[1] Division of Respiratory Medicine, Department of Medicine, Vancouver General Hospital, UBC, Vancouver, B.C., Canada;Faculty of Medicine, University of Manitoba, Winnipeg, MB, Canada;Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN, USA;UBC James Hogg Research Center, Providence Heart + Lung Institute, St. Paul's Hospital, Vancouver, B.C., Canada

关键词: chronic obstructive pulmonary disease;    polymorphism;    Heme oxygenase;   

Others  :  1177992
DOI  :  10.1186/1471-2350-12-117

 received in 2011-03-09, accepted in 2011-09-08,  发布年份 2011

【 摘 要 】

Background

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 HMOX1 polymorphisms were associated with lung function in COPD patients and whether the variants had functional effects.

Methods

We genotyped five single nucleotide polymorphisms (SNPs) in the HMOX1 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 HMOX1 promoter polymorphisms and the effect of these polymorphisms on H₂O₂ and hemin-stimulated gene expression was determined. The effect of the HMOX1 rs2071749 SNP on gene expression in alveolar macrophages was investigated.

Results

We found a nominal association (p = 0.015) between one intronic HMOX1 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 HMOX1. We tested rs3761439 and two other putatively functional polymorphisms (rs2071746 and the (GT)_n polymorphism) in reporter gene assays but no significant effects on gene expression were found. There was also no effect of rs2071749 on HMOX1 gene expression in alveolar macrophages.

Conclusions

We found no association of the five HMOX1 tag SNPs with lung function decline and no evidence that the three promoter polymorphisms affected the regulation of the HMOX1 gene.

【 授权许可】

   
2011 Tanaka et al; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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