The −444A/C Polymorphism in the LTC4S Gene and the Risk of Asthma: A Meta-analysis

Zhang, Yonggang; Huang, Honglang; Huang, Jingsheng; Xiang, Zhangpeng; Tian, Chao; Fan, Hong

doi:10.1016/j.arcmed.2012.08.003

Cited by 10 publications

(10 citation statements)

References 17 publications

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“…However, the activity of this polymorphic promoter is reported to cause alterations in CysLT production which are associated with severe asthma (Sampson et al, 2000; Kedda et al, 2004). This relationship has been confirmed by meta-analysis (Zhang et al, 2012). …”

Section: Leukotriene Synthesismentioning

confidence: 58%

Cysteinyl Leukotrienes Pathway Genes, Atopic Asthma and Drug Response: From Population Isolates to Large Genome-Wide Association Studies

et al. 2016

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Genetic variants associated with asthma pathogenesis and altered response to drug therapy are discussed. Many studies implicate polymorphisms in genes encoding the enzymes responsible for leukotriene synthesis and intracellular signaling through activation of seven transmembrane domain receptors, such as the cysteinyl leukotriene 1 (CYSLTR1) and 2 (CYSLTR2) receptors. The leukotrienes are polyunsaturated lipoxygenated eicosatetraenoic acids that exhibit a wide range of pharmacological and physiological actions. Of the three enzymes involved in the formation of the leukotrienes, arachidonate 5 lipoxygenase 5 (ALOX5), leukotriene C4 synthase (LTC4S), and leukotriene hydrolase (LTA4H) are all polymorphic. These polymorphisms often result in variable production of the CysLTs (LTC4, LTD4, and LTE4) and LTB4. Variable number tandem repeat sequences located in the Sp1-binding motif within the promotor region of the ALOX5 gene are associated with leukotriene burden and bronchoconstriction independent of asthma risk. A 444A > C SNP polymorphism in the LTC4S gene, encoding an enzyme required for the formation of a glutathione adduct at the C-6 position of the arachidonic acid backbone, is associated with severe asthma and altered response to the CYSLTR1 receptor antagonist zafirlukast. Genetic variability in the CysLT pathway may contribute additively or synergistically to altered drug responses. The 601 A > G variant of the CYSLTR2 gene, encoding the Met201Val CYSLTR2 receptor variant, is associated with atopic asthma in the general European population, where it is present at a frequency of ∼2.6%. The variant was originally found in the founder population of Tristan da Cunha, a remote island in the South Atlantic, in which the prevalence of atopy is approximately 45% and the prevalence of asthma is 36%. In vitro work showed that the atopy-associated Met201Val variant was inactivating with respect to ligand binding, Ca2+ flux and inositol phosphate generation. In addition, the CYSLTR1 gene, located at Xq13-21.1, has been associated with atopic asthma. The activating Gly300Ser CYSLTR1 variant is discussed. In addition to genetic loci, risk for asthma may be influenced by environmental factors such as smoking. The contribution of CysLT pathway gene sequence variants to atopic asthma is discussed in the context of other genes and environmental influences known to influence asthma.

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Section: Leukotriene Synthesismentioning

confidence: 58%

Cysteinyl Leukotrienes Pathway Genes, Atopic Asthma and Drug Response: From Population Isolates to Large Genome-Wide Association Studies

et al. 2016

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“…In the present study, promoters were differentially methylated within the 17β-hydroxysteroid dehydrogenase type 14 (HSD17B14), leukotriene C4 synthase (LTC4S), folate receptor 3 (FOLR3), alcohol dehydrogenase 7 (ADH7), and adiponectin receptor 2 (ADIPOR2) genes that are involved in steroid, eicosanoid, folate, retinol, and glucose and lipid metabolism, respectively [37][38][39][40][41]. Like the CYSLTR1 gene, LTC4S polymorphisms were associated with asthma risk and drug responsiveness in different ethnic populations [42][43][44][45].…”

Section: Discussionmentioning

confidence: 77%

Epigenome-wide analysis of common warts reveals aberrant promoter methylation

et al. 2020

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Epigenetic alteration of host DNA is a common occurrence in both low-and high-risk human papillomavirus (HPV) infection. Although changes in promoter methylation have been widely studied in HPV-associated cancers, they have not been the subject of much investigation in HPV-induced warts, which are a temporary manifestation of HPV infection. The present study sought to examine the differences in promoter methylation between warts and normal skin. To achieve this, DNA was extracted from 24 paired wart and normal skin samples and inputted into the Infinium MethylationEPIC BeadChip microarray. Differential methylation analysis revealed a clear pattern of hyper-and hypomethylation in warts compared to normal skin, and the most differentially methylated promoters were found within the EIF3EP2, CYSLTR1, C10orf99, KRT6B, LAMA4, and H3F3B genes as well as the C9orf30 pseudogene. Moreover, pathway analysis showed that the H3F3A, CDKN1A, and MAPK13 genes were the most common regulators among the most differentially methylated promoters. Since the tissue samples were excised from active warts, however, this differential methylation could either be a cellular response to HPV infection or an HPV-driven process to establish the wart and/or promote disease progression. Conclusively, it is apparent that HPV infection alters the methylation status of certain genes to possibly initiate the formation of a wart and maintain its presence.

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“…In the study in the Polish population, which was the first study, it was possible to distinguish between NERD and ATA [ 71 ]. However, a recent meta-analysis did not show any significant results in NERD; the only significant results were obtained in the ATA and Caucasian subgroups [ 72 ]. In a Korean study, ALOX5 (5-LO enzyme gene) ht1 [G-C-G-A] was found to be significantly higher in NERD than in ATA in the 4SNP (−1708G>A, 21C>T, 270G>A, and 1728G>A) [ 73 ].…”

Section: Biomarkers Of Nerdmentioning

confidence: 99%

Potential Biomarkers for NSAID-Exacerbated Respiratory Disease

Park

Choi

Jung

et al. 2017

Mediators of Inflammation

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Asthma is a common chronic disease with several variant phenotypes and endotypes. NSAID-exacerbated respiratory disease (NERD) is one such endotype characterized by asthma, chronic rhinosinusitis (CRS) with nasal polyps, and hypersensitivity to aspirin/cyclooxygenase-1 inhibitors. NERD is more associated with severe asthma than other asthma phenotypes. Regarding diagnosis, aspirin challenge tests via the oral or bronchial route are a standard diagnostic method; reliable in vitro diagnostic tests are not available. Recent studies have reported various biomarkers of phenotype, diagnosis, and prognosis. In this review, we summarized the known potential biomarkers of NERD that are distinct from those of aspirin-tolerant asthma. We also provided an overview of the different NERD subgroups.

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The −444A/C Polymorphism in the LTC4S Gene and the Risk of Asthma: A Meta-analysis

Cited by 10 publications

References 17 publications

Cysteinyl Leukotrienes Pathway Genes, Atopic Asthma and Drug Response: From Population Isolates to Large Genome-Wide Association Studies

Cysteinyl Leukotrienes Pathway Genes, Atopic Asthma and Drug Response: From Population Isolates to Large Genome-Wide Association Studies

Epigenome-wide analysis of common warts reveals aberrant promoter methylation

Potential Biomarkers for NSAID-Exacerbated Respiratory Disease

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