Novel variants in the PRDX6 Gene and the risk of Acute Lung Injury following major trauma

BMC Medical Genetics

Jason D Christie¹  Steven M Albelda²  Aron B Fisher³  Sheldon I Feinstein³  A Russell Localio¹  Scarlett Bellamy¹  Robert Gallop¹  Paul N Lanken²  Rui Feng¹  Mingyao Li¹  Nuala Meyer²  Richard Aplenc⁴  Melanie Rushefski⁴ 

[1] Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, 423 Guardian Drive, Philadelphia, 19104, USA;Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Pennsylvania School of Medicine, 3600 Spruce Street, Philadelphia, 19104, USA;Institute for Environmental Medicine, University of Pennsylvania, 3620 Hamilton Walk, Philadelphia, 19104, USA;Division of Oncology, Children's Hospital of Philadelphia, 34th Street and Civic Center Boulevard, Philadelphia, 19104, USA

关键词: Genetic Polymorphisms;    Oxidant Stress;    Acute Lung Injury;    Peroxiredoxin;   

Others  :  1178033
DOI  :  10.1186/1471-2350-12-77

 received in 2010-07-15, accepted in 2011-05-31,  发布年份 2011

【 摘 要 】

Background

Peroxiredoxin 6 (PRDX6) is involved in redox regulation of the cell and is thought to be protective against oxidant injury. Little is known about genetic variation within the PRDX6 gene and its association with acute lung injury (ALI). In this study we sequenced the PRDX6 gene to uncover common variants, and tested association with ALI following major trauma.

Methods

To examine the extent of variation in the PRDX6 gene, we performed direct sequencing of the 5' UTR, exons, introns and the 3' UTR in 25 African American cases and controls and 23 European American cases and controls (selected from a cohort study of major trauma), which uncovered 80 SNPs. In silico modeling was performed using Patrocles and Transcriptional Element Search System (TESS). Thirty seven novel and tagging SNPs were tested for association with ALI compared with ICU at-risk controls who did not develop ALI in a cohort study of 259 African American and 254 European American subjects that had been admitted to the ICU with major trauma.

Results

Resequencing of critically ill subjects demonstrated 43 novel SNPs not previously reported. Coding regions demonstrated no detectable variation, indicating conservation of the protein. Block haplotype analyses reveal that recombination rates within the gene seem low in both Caucasians and African Americans. Several novel SNPs appeared to have the potential for functional consequence using in silico modeling. Chi² analysis of ALI incidence and genotype showed no significant association between the SNPs in this study and ALI. Haplotype analysis did not reveal any association beyond single SNP analyses.

Conclusions

This study revealed novel SNPs within the PRDX6 gene and its 5' and 3' flanking regions via direct sequencing. There was no association found between these SNPs and ALI, possibly due to a low sample size, which was limited to detection of relative risks of 1.93 and above. Future studies may focus on the role of PRDX6 genetic variation in other diseases, where oxidative stress is suspected.

【 授权许可】

   
2011 Rushefski et al; licensee BioMed Central Ltd.

【 图 表 】

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