Expression of 5-Lipoxygenase and 5-Lipoxygenase-Activating Protein mRNAs in the Peripheral Blood Leukocytes of Asthmatics

Koshino, Takeshi; Takano, Shizuko; Houjo, Takako; Sugiyama, Yasuyuki; Kudo, Koichiro; Kihara, Hidetoshi; Kitani, Seiichi; Takaishi, Toshiaki; Hirai, Koichi; Itō, Kōji; Morita, Yutaka

doi:10.1006/bbrc.1998.8789

Cited by 38 publications

(24 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The relative expression of 5-lipoxygenase mRNA in individuals with BA (without or with E254K) increased 2.6-or 3.1-fold above that in non-allergic subjects. This result supports the opinion of Koshino et al that the upregulation of 5-lipoxygenase mRNA might be involved in the increased leukotriene synthesis and play an important role in the pathogenesis of asthma (11). In this study, the relative expression of 5-lipoxygenase mRNA was higher in individuals with BA and with E254K than in those with BA but without E254K.…”

Section: Discussionsupporting

confidence: 92%

“…Chronic airway inflammation is a feature of asthma. Recently, evidence has demonstrated that leukotriene C4, D4 and E4 increase in the serum, urine and exhaled breath condensate (EBC) of asthma patients (11,15). The first committed enzyme in the biosynthetic pathway leading to the production of leukotrienes is 5-lipoxygenase.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, the 5-lipoxygenaseactivating protein (FLAP) promoter gene polymorphisms (21A repeat and 18A repeat) were reported to be associated with BA (10). Recent evidence demonstrated that upregulation of 5-LO and FLAP mRNAs might be involved in the increased leukotriene synthesis and play an important role in the pathogenesis of BA (11).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

A novel polymorphism, E254K, in the 5-lipoxygenase gene associated with bronchial asthma

Bai

Matsui²,

Ohnishi³

et al. 2008

Int J Mol Med

View full text Add to dashboard Cite

Abstract. Cysteinyl-leukotrienes are important proinflammatory mediators in bronchial asthma (BA) and are derived from arachidonic acid by the action of 5-lipoxygenase. We identified a novel polymorphism, c.760 G>A (E254K), in exon 6 of the 5-lipoxygenase gene (5-LO). This substitution was detected in 11 out of 180 patients with BA, but not in any of the 150 non-allergic subjects. The frequency of c.760 G>A showed a significant difference between BA and non-allergic subjects (P=0.0007). The c.760 G>A polymorphism existed at the surface edge of the C-terminal catalytic domain, and the E-to-K substitution changed the charge of the side chain from negative to positive. Thus, our results suggest that E254K in the 5-LO might be associated with BA.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A novel polymorphism, E254K, in the 5-lipoxygenase gene associated with bronchial asthma

Bai

Matsui²,

Ohnishi³

et al. 2008

Int J Mol Med

View full text Add to dashboard Cite

show abstract

“…Further studies of the ALOX5 promoter VNTR are needed in ALOX5AP, which is a 18-kDa nuclear membrane protein, has been postulated to play an essential role in the transfer of arachidonic acid to ALOX5 (Kennedy et al 1991). In patients with asthma, increased expression of ALOX5AP and ALOX5 mRNAs has been reported in peripheral blood leukocytes by the reverse transcriptionpolymerase chain reaction (RT-PCR) technique (Koshino et al 1998). Koshino et al (1999) have shown that the frequency of the monopolymer A repeats (21 A repeats, 95-73 bp upstream from the ATG transcription start site) in the polyadenyl region of the ALOX5AP promoter gene is significantly higher in asthmatics than in controls, but they have not identified the effects of these monopolymer A repeats of the ALOX5AP promoter gene on its promoter function.…”

Section: Discussionmentioning

confidence: 99%

Leukotriene-related gene polymorphisms in ASA-intolerant asthma: an association with a haplotype of 5-lipoxygenase

et al. 2004

View full text Add to dashboard Cite

A recent study has demonstrated the possible involvement of a leukotriene C4 synthase (LTC4S) gene polymorphism in ASA-intolerant asthma (AIA) in a Polish population, whereas no significant association was noted in other populations. To investigate the role of genetic polymorphism in AIA development, we screened single nucleotide polymorphisms (SNPs) of the key enzymes involved in arachidonate metabolism, and the cysteinyl leukotriene receptor 1 (CYSLTR1) in a large Korean population with AIA: 93 AIA and 181 ASA-tolerant asthma (ATA) patients, and 123 normal controls. The single-base extension method was used to genotype SNPs in 5-lipoxygenase (ALOX5, -1708G→A, 21C→T, 270G→A, 1728G→A), ALOX5-activating protein (ALOX5AP, 218A→G), prostaglandin-endoperoxide synthase 2 (PTGS2, COX2, -162C→G, 10T→G, R228H, V511A), LTC4S (-444A→C), and CYSLTR1 (927T→C). Haplotype analyses were undertaken for the SNPs in ALOX5. No significant differences in allele and genotype frequencies of single SNPs were observed between the patient groups (P>0.05). However, the frequency of the ALOX5-ht1 [G-C-G-A] haplotype in the AIA group was significantly higher than its frequency in the ATA group with a probability (P) of 0.01, odds ratio (OR) of 5.0, and 95% confidence interval (95%CI) of 1.54-17.9, and in the normal controls (P=0.03, OR=4.5, 95%CI=1.1-18.4), by using a dominant model. These results suggest a lack of association between the ALOX5AP, PTGS2, LTC4S, and CYSLTR1 gene polymorphisms and the AIA phenotype in the Korean population. However, the possible involvement of ALOX5-ht1 [G-C-G-A] in AIA development is suggested.

show abstract

“…Polymorphisms in ALOX5 and also in 5-lipoxygenase-activating-protein (FLAP) are associated with the excessive production of leukotrienes (Koshino et al 1999). The levels of ALOX5 and FLAP messenger RNA -the RNA molecule that is the blueprint for the protein -are increased in peripheral blood leukocytes from asthmatics (Koshino et al 1998). In addition, the concentrations of leukotrienes in sputum were greater in patients with asthma than in nonasthmatic subjects (Ogawa and Calhoun 2006).…”

Section: Alox5mentioning

confidence: 99%

Asthma patients with specific genotypes identified for fish oil treatment trial

Allayee¹,

Davis²,

Fortenko³

et al. 2011

Cal Ag

View full text Add to dashboard Cite

The lifetime prevalence of asthma in California is nearly 20%, and better therapies are needed to manage this common chronic disease. Fish oils containing omega-3 fatty acids are considered a potential therapy for asthma and other inflammatory diseases. Fish oil inhibits the production of arachidonic acid 5-lipoxygenase (ALOX5), an enzyme that exacerbates the lung inflammation that causes asthma. We discuss the genetics of asthma and our preliminary results using a strategy to identify the subgroup of patients who may respond well to treatment with fish oil. These findings, and others, suggest that certain gene polymorphisms of the ALOX5 gene predispose patients to the increased production of inflammatory leukotrienes. Our clinical trials will test the hypothesis that patients with moderate to severe asthma, and with specific high-risk ALOX5 gene sequence variations, will have fewer asthma symptoms when treated with fish oil. The strategy is to decrease the total burden of leukotriene production by supplementing with omega-3 polyunsaturated fatty acids. These studies will also help determine whether genotyping or metabolic profiling (for example, with exhaled breath condensate) can help establish "personalized medicine" for asthma.

show abstract

Expression of 5-Lipoxygenase and 5-Lipoxygenase-Activating Protein mRNAs in the Peripheral Blood Leukocytes of Asthmatics

Cited by 38 publications

References 19 publications

A novel polymorphism, E254K, in the 5-lipoxygenase gene associated with bronchial asthma

A novel polymorphism, E254K, in the 5-lipoxygenase gene associated with bronchial asthma

Leukotriene-related gene polymorphisms in ASA-intolerant asthma: an association with a haplotype of 5-lipoxygenase

Asthma patients with specific genotypes identified for fish oil treatment trial

Contact Info

Product

Resources

About