Cysteinyl leukotriene receptor 1 promoter polymorphism is associated with aspirin‐intolerant asthma in males

Kim, S.H.; Oh, Jung Mi; Kim, Y.S.; Palmer, Lyle J.; Suh, Chang‐Hee; Nahm, Dong Ho; Park, Hae‐Sim

doi:10.1111/j.1365-2222.2006.02457.x

Cited by 87 publications

(73 citation statements)

References 34 publications

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“…In a Caucasian Spanish population, Sanz et al reported the minor allele of the synonymous coding SNP 927 T>C (rs320995) to be associated with asthma (130 asthma vs 78 controls) (123), but Arriba-Mendez et al observed this association only in male subjects (87 asthma vs 79 controls, p < 0.008) (128), whereas two other groups could not detect any association in a Caucasian British and a Korean population (109,129). Although this was not reproduced in a Japanese study (137 families) (130), Kim et al found an association of the three SNPs in the CYSLTR1 promoter with aspirin intolerant asthma among male Koreans (340 individuals, p < 0.03) (131). The authors also observed an association of these same alleles with atopy among female aspirin intolerant asthmatic individuals (p = 0.03) (131).…”

Section: Cyslt Receptorsmentioning

confidence: 97%

“…In a high prevalence asthmatic population with a founder effect, Thompson et al observed the minor allele of the coding polymorphism 899 G>A (Gly300Ser) to be associated with both asthma (p = 0.005) and atopy (OR = 4; 95% CI:1.2-13.3) in female subjects (132). Other studies have detected an association of the promoter or coding SNPs with allergic phenotypes such as high total IgE (p = 0.003) (131) and AD (OR = 4.97; 95% CI:1.29-19.13) (128), which could not be reproduced elsewhere (129,130). Overall, despite these discrepancies, most studies agree that there is an association between CYSLTR1 genetic variation and allergic phenotypes and that this association is gender specific.…”

Section: Cyslt Receptorsmentioning

confidence: 99%

“…Although this was not reproduced in a Japanese study (137 families) (130), Kim et al found an association of the three SNPs in the CYSLTR1 promoter with aspirin intolerant asthma among male Koreans (340 individuals, p < 0.03) (131). The authors also observed an association of these same alleles with atopy among female aspirin intolerant asthmatic individuals (p = 0.03) (131). Interestingly, we have preliminary evidence that a promoter SNP is associated with atopy incidence in a large Caucasian population (unpublished data, Duroudier et al ) In addition, in a family-based association study (341 Caucasian families), the coding SNP 927 T>C which is in high linkage disequilibrium with the promoter SNP rs2806489 was associated with atopy severity (p = 0.015), which was more significant in female asthma subjects (p = 0.0087) (129).…”

Section: Cyslt Receptorsmentioning

confidence: 99%

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Leukotriene pathway genetics and pharmacogenetics in allergy

Duroudier

Tulah

Sayers

2009

Allergy

102

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Leukotrienes (LT) are a family of potent eicosanoid lipid mediators with central importance in disease processes such as inflammation and proliferation most notably observed in allergic conditions like asthma (1). There are two general classes of LT according to the presence of a cysteine residue in their amino acid chain: the cysteinyl leukotrienes (CysLTs) including LTC 4 , LTD 4 and LTE 4 and the dihydroxyleukotriene LTB 4 (2). The 5-lipoxygenase pathwayLeukotrienes are produced in a multi-step enzyme pathway called the 5-lipoxygenase (5-LO) pathway, which is active in leucocytes such as neutrophils, eosinophils, mast cells and monocytes (Fig. 1). Arachidonic acid is the precursor for LT synthesis and is hydrolysed from the plasma membrane by cytosolic phospholipase A 2 (and other isoforms) (3, 4) in a calcium-dependent process (5). Upon activation, the rate-limiting enzyme 5-LO oxygenates first free arachidonic acid into the unstable intermediate 5-hydroperoxyeicosatetraenoic acid (5-HPETE) which is then either hydrolysed to 5-hydroxyeicosatetraenoic acid (5-HETE) or transformed into the unstable epoxide leukotriene A 4 (LTA 4 ) by forming a conjugated triene system through dehydration (6). 5-LO translocates from either the nucleus (in macrophages) or cyotosol (in neutrophils) to the nuclear envelope in response to cell activation (7,8). This movement occurs as 5-LO is dependent on a 5-LO activating protein (FLAP) for its function. FLAP remains associated with the nuclear membrane (9) and acts as a Ôtransfer proteinÕ presenting arachidonic acid to 5-LO, a system which allows the favourable conversion of 5-HPETE to LTA 4 compared to 5-HETE (10). Both 5-LO and FLAP are expressed in cells of myeloid lineage (11) restricting the pathway to these cell types. LTA 4 can be further metabolised to the cysteinyl leukotrienes (CysLTs) or LTB 4 . The specific glutathione S-transferase leukotriene C 4 synthase (LTC 4 S) conjugates LTA 4 to form LTC 4 which can then be rapidly converted to LTD 4 by a gammaglutamyl transpeptidase and to LTE 4 by a dipeptidase once exported out the cell by membrane transport proteins such as multi-drug related protein 1 (MRP1) (12-15). A specific zinc metallohydrolase, LTA 4 hydrolase (LTA 4 H) is responsible for the conversion of LTA 4 to LTB 4 (16). CysLTs and LTB 4 act on different G-protein coupled receptors (GPCRs). Each bind to at least two different receptors: CysLTs to CYSLTR1 and CYSLTR2 and LTB 4 to LTB 4 R1 and LTB 4 R2 (or BLT1 and BLT2) (17).Leukotrienes (LT) are biologically active lipid mediators known to be involved in allergic inflammation. Leukotrienes have been shown to mediate diverse features of allergic conditions including inflammatory cell chemotaxis/activation and smooth muscle contraction. Cysteinyl leukotrienes (LTC 4 , LTD 4 and, LTE 4 ) and the dihydroxy leukotriene LTB 4 are generated by a series of enzymes/ proteins constituting the LT synthetic pathway or 5-lipoxygenase (5-LO) pathway. Their function is mediated by interacting with multiple receptors. Leukotr...

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Section: Cyslt Receptorsmentioning

confidence: 97%

Section: Cyslt Receptorsmentioning

confidence: 99%

Section: Cyslt Receptorsmentioning

confidence: 99%

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Leukotriene pathway genetics and pharmacogenetics in allergy

Duroudier

Tulah

Sayers

2009

Allergy

102

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“…Briefly, 2×10 5 cells were seeded in 24-well plates and transfected with 0.5 μg of the reporter constructs and 0.5 μg of pSV-β-galactosidase control vector using a microporator (Incyto, Suwon, Korea) at 1,300 V and pulse width of 30 ms. At 48 h posttransfection, the cells were lysed and assayed for firefly luciferase activity according to the manufacturer's instructions (Promega). The transfections and luciferase assays were repeated four times (twelve times in total) according to the method described previously [19].…”

Section: Study Subjectsmentioning

confidence: 99%

“…The bronchoconstrictive effects of CysLTs are exerted via their G-coupled receptor, CysLT receptor type 1 (CysLTR1) [18], and these effects can be efficiently reversed by CysLTR1 antagonist [7,8]. We have previously reported the potential contribution of a CysLTR1 promoter polymorphism to AIA susceptibility compared to aspirin-tolerant asthma (disease control) [19].…”

Section: Introductionmentioning

confidence: 99%

Differential Contribution of the CysLTR1 Gene in Patients with Aspirin Hypersensitivity

et al. 2007

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In this study, we compared the roles of CysLT receptor type 1 (CysLTR1) and leukotriene C4 synthase (LTC4S) gene polymorphisms in two major aspirin-related allergic diseases, aspirin-intolerant asthma (AIA) and aspirin-induced chronic urticaria/angioedema (AICU). CysLTR1-634C>T and LTC4S-444A>C polymorphisms were genotyped and its functional effect on the promoter activity was compared. As in vivo functional study, changes of peripheral mRNA level of CysLTR1 were measured by real-time PCR before and after aspirin challenge. A significant association was found for the CysLTR1 promoter polymorphism and the AIA phenotype compared to AICU (P=0.015). In U937 cells, the variant genotype reporter construct showed significantly higher promoter activity than the common genotype (P < 0.05). The CysLTR1 mRNA levels increased significantly after aspirin challenge in AIA patients (P=0.013). In conclusion, the CysLTR1 polymorphism may contribute to develop to the AIA phenotype and be used as a genetic marker for differentiating two major aspirin hypersensitivity phenotypes.

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Pharmacogenetics of Asthma

Hawkins

Peters

2008

Methods in Molecular Biology™

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Asthma is a common disease characterized by airway inflammation and bronchorestriction. There are several common categories of medications for treating asthma; however, not all asthmatics have the same response to these medications, some of which are adverse responses that are potentially life threatening. Because interindividual responses to asthma medications can vary considerably, the potential for genetic contributions to variable drug responses is significant. This chapter reviews the most common biological pathways targeted by asthma therapy and briefly discusses the genetic contribution to varied responses to asthma therapy for four common types of asthma medications: beta-agonists, anticholinergics, leukotriene modifiers, and corticosteroids.

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Cysteinyl leukotriene receptor 1 promoter polymorphism is associated with aspirin‐intolerant asthma in males

Cited by 87 publications

References 34 publications

Leukotriene pathway genetics and pharmacogenetics in allergy

Leukotriene pathway genetics and pharmacogenetics in allergy

Differential Contribution of the CysLTR1 Gene in Patients with Aspirin Hypersensitivity

Pharmacogenetics of Asthma

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