Association of 5-lipoxygenase gene polymorphisms with bronchial asthma

Bai,Chunying; Yu,Xiaoming; Yun,Rui; Shi,Tiewei; Zhang,Chaojun; Zhou,Jing; Sachurangui,; Tong,Lijuan; Li,Xiujun; Gao,Lifeng

doi:10.3892/etm.2012.712

Association of 5-lipoxygenase gene polymorphisms with bronchial asthma

Authors:
- Chunying Bai
- Xiaoming Yu
- Rui Yun
- Tiewei Shi
- Chaojun Zhang
- Jing Zhou
- Sachurangui
- Lijuan Tong
- Xiujun Li
- Lifeng Gao
View Affiliations

Affiliations: Molecular Medicine Research Center, School of Medical Science, Chifeng University, P.R. China, Department of Pediatrics, First Affiliated Hospital of Chifeng University, P.R. China, Department of Pneumology, First Affiliated Hospital of Chifeng University, P.R. China, Department of Pediatrics, Chifeng City Hospital, Chifeng, Inner Mongolia, P.R. China
Published online on: September 17, 2012 https://doi.org/10.3892/etm.2012.712
Pages: 967-971

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Leukotrienes are important pro-inflammatory mediators in bronchial asthma (BA) and are derived from arachidonic acid by the action of 5-lipoxygenase (5-LO). We investigated the association of 5-LO gene polymorphisms with BA. Thirty-six single-nucleotide polymorphisms (SNPs) of the 5-LO gene, as referenced in the dbSNP gene bank, were analyzed with sequencing and allele-specific PCR (AS-PCR) in genomic DNA from individuals with BA and controls. Of these 36 SNPs, 4 were identified in our study. The c.760 G>A (E254K) (rs2228065) was detected in 15 out of 215 BA patients and 6 out of 212 controls (P<0.05). There were no differences in the frequencies of the other three silent polymorphisms, rs2228064 (c.270 G>A), rs116961353 (c.780G>A) and rs2229136 (c.1728 A>G) between individuals with BA and controls (P>0.05). With our designed primers for AS-PCR, the detection of the 5-LO gene E254K polymorphism was clear and accurate, and the genotype was directly distinguished. Our findings contribute to the evaluation of one of the genetic risk factors for BA and we report an accurate and simple method to rapidly detect the 5-LO E254K polymorphism. It is important to further study the correlation between drug response in BA patients using 5-LO inhibitors with the E254K polymorphism in the clinic.

View References

1	Sanak M: Genetic Variance of 5-lipoxygenase Metabolic Pathway in Bronchial Asthma. International Review of Asthma. 4:70–80. 2002.
2	Wong WS and Koh DS: Advances in immunopharmacology of asthma. Biochem Pharmacol. 59:1323–1335. 2000. View Article : Google Scholar : PubMed/NCBI
3	Chen XS, Sheller JR, Johnson EN and Funk CD: Role of leukotrienes revealed by targeted disruption of the 5-lipoxygenase gene. Nature. 372:179–182. 1994. View Article : Google Scholar : PubMed/NCBI
4	Samuelsson B: Leukotrienes: mediators of immediate hypersensitivity reactions and inflammation. Science. 220:568–575. 1983. View Article : Google Scholar : PubMed/NCBI
5	Samuelsson B, Dahlén SE, Lindgren JA, Rouzer CA and Serhan CN: Leukotrienes and lipoxins: structures, biosynthesis, and biological effects. Science. 237:1171–1176. 1987. View Article : Google Scholar : PubMed/NCBI
6	Lewis RA, Austen KF and Soberman RJ: Leukotrienes and other products of the 5-lipoxygenase pathway. Biochemistry and relation to pathobiology in human diseases. N EngI J Med. 323:645–655. 1990. View Article : Google Scholar
7	Funk CD, Hoshiko S, Matsumoto T, Radmark O and Samuelsson B: Characterization of the human 5-lipoxygenase gene. Proc Natl Acad Sci USA. 86:2587–2591. 1989. View Article : Google Scholar : PubMed/NCBI
8	Drazen JM and Silverman ES: Genetic determinants of 5-lipoxygenase transcription. Int Arch Allergy Immunol. 118:275–278. 1999. View Article : Google Scholar
9	Silverman ES and Drazen JM: Genetic variations in the 5-lipoxygenase core promoter. Description and functional implications. Am J Respir Crit Care Med. 161:S77–S80. 2000. View Article : Google Scholar : PubMed/NCBI
10	Bai C, Matsui E, Ohnishi H, et al: A novel polymorphism, E254K, in the 5-lipoxygenase gene associated with bronchial asthma. Int J Mol Med. 21:139–144. 2008.PubMed/NCBI
11	Proceedings of the ATS workshop on refractory asthma. Am J Respir Crit Care Med. 162:2000.
12	Bai C, Zhou J, Rui Y, et al: Economical and Effective Method for Extract Blood Genomic DNA. Chinese journal of Laboratory Medicine and Clinic. 7:1795–1798. 2010.
13	Boyce JA, Broide D, Matsumoto K and Bochner BS: Advances in mechanisms of asthma, allergy, and immunology in 2008. J Allergy Clin Immunol. 123:569–574. 2009. View Article : Google Scholar : PubMed/NCBI
14	De Caterina R and Zampolli A: From asthma to atherosclerosis -5-lipoxygenase, leukotrienes, and inflammation. New Eng J Med. 350:4–7. 2004.PubMed/NCBI
15	In KH, Silverman ES, Asano K, Beier D, Fischer AR, Keith TP, et al: Mutations in the human 5-lipoxygenase gene. Clin Rev Allergy Immunol. 17:59–69. 1999. View Article : Google Scholar : PubMed/NCBI
16	van den Heuvel MM, Vanhee DD, Postmus PE, et al: Functional and phenotypic differences of monocyte-derived dendritic cells from allergic and nonallergic patients. Allergy Clin Immunol. 101:90–95. 1998.PubMed/NCBI
17	Galli SJ: Complexity and reducdancy in the pathogenesis of asthma: reassessing the roles of mast cells and T cells. J Exp Med. 186:343–347. 1997. View Article : Google Scholar : PubMed/NCBI
18	Krouwels FH, Kerstens LC, van der Maarel HW, Degenhart HJ and Neijens HJ: Density of eosinophils reflects activity of disease in allergic asthmatic children. Clin Exp Allergy. 25:1171–1178. 1995. View Article : Google Scholar : PubMed/NCBI
19	Berretta F, Butler RH, Diaz G, Sanarico N, Arroyo J, Fraziano M, et al: Detailed analysis of the effects of Glu/Lys beta69 human leukocyte antigen-DP polymorphism on peptide-binding specificity. Tissue Antigens. 62:459–471. 2003. View Article : Google Scholar : PubMed/NCBI