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  • 1
    Electronic Resource
    Electronic Resource
    Polymorphism of the mast cell chymase gene (CMA1) promoter region: lack of association with asthma but association with serum total immunoglobulin E levels in adult atopic dermatitis (2004)
    Oxford, UK : Blackwell Science Ltd
    Clinical & experimental allergy 34 (2004), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Mast cell chymase has the potential to be an important mediator of inflammation and remodelling in the asthmatic lung. Previous studies have examined association between promoter polymorphism of the chymase gene (CMA1) and allergic phenotypes but the significance of this polymorphism is unclear. We have examined association of a CMA1 variant in relation to asthma in a large UK Caucasian family cohort.Methods A polymorphism of the CMA1 gene promoter (−1903G/A) was genotyped in 341 asthmatic families and in 184 non-asthmatic adults recruited from the UK PCR-RFLP based genotyping. Association with asthma diagnosis, atopy, specific and total IgE, and atopy and asthma severity was examined.Results Case–control studies did not reveal a significant difference in allele frequency between asthmatics and controls. A significant association was found between CMA1 genotypes and total IgE levels in subjects with self-reported eczema that remained significant after correction for multiple testing (median total serum IgE GG 297 kU/L, GA 144 kU/L, AA 48.4 kU/L, Pc=0.0032).Conclusion These data suggest that CMA1 promoter polymorphism does not contribute to asthma susceptibility or severity but may be involved in regulating IgE levels in patients with eczema.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2222.2004.02000.x
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  • 2
    Electronic Resource
    Electronic Resource
    Lack of evidence of a significant association between HLA-DR, DQ and DP genotypes and atopy in families with HDM allergy (1996)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical & experimental allergy 26 (1996), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background HLA class II genetic polymorphism has been variably implicated in susceptibility to specific immune responsiveness to house dust mite (HDM) allergens, and may also influence the development of atopy.Objective In order to assess accurately the influence of HLA alleles in the atopic immune response, we typed 22 families selected from 131 previously obtained randomly selected families (i.e. without regard to atopy or asthma), chosen on the basis of two or more members having skin prick reactivity to HDM.Methods Each individual was fully typed for HLA-DRB1, DQA1, DQB1 and DPB1 class II alleles using a combination of sequence-specific oligonucleotide probes (SSOP) and sequence-specific primer (SSP) polymerase chain reaction (PCR) typing and direct sequencing.Results Using appropriate statistical tests, no significant allelic associations were found between any DRBl, DQB1 or DPBl alleles and atopy or skin prick reactivity to Dermataphagoides pteronyssinus (Der p) or D. farinae (Der f). However, positive associations were found between DQA 1*0301 and skin prick reactivity to Der f (P= 0.009) and atopy (P= 0.027). Sib-pair analysis revealed no significant sharing of alleles between affected sib pairs for any of the phenotypes studied.Conclusion These results fail to confirm a previously reported association between the DRB1*04 and 07 haplotypes and atopy, and suggest that HLA class II restriction does not play a major role in the development of the IgE response to domestic house dust mite allergens in the British population.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2222.1996.tb00500.x
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  • 3
    Electronic Resource
    Electronic Resource
    Toll-like receptor polymorphisms and allergic disease: interpreting the evidence from genetic studies (2004)
    Oxford, UK : Blackwell Science Ltd
    Clinical & experimental allergy 34 (2004), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2222.2004.01893.x
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  • 4
    Electronic Resource
    Electronic Resource
    Association of thromboxane A2 receptor gene polymorphism with the phenotype of acetyl salicylic acid-intolerant asthma (2005)
    Oxford, UK : Blackwell Science Ltd
    Clinical & experimental allergy 35 (2005), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background and objective The thromboxane A2 receptor (TBXA2R) is a receptor for a potent bronchoconstrictor, TBXA2 which is known to be related to bronchial asthma and myocardial infarction. TBXA2R antagonist and TBX synthase inhibitors have been found to be effective in the management of asthmatic patients. This study was aimed to evaluate whether genetic variants of TBXA2R may be related with development of acetyl salicylic acid (ASA)-intolerant asthma (AIA).Methods TBXA2R gene polymorphisms (TBXA2R+795T〉C, TBXA2R+924T〉C) were determined using a single-base extension method in 93 AIA patients compared with 172 patients with ASA-tolerant asthma (ATA) and 118 normal controls (NCs) recruited from the Korean population. HLA DPB1*0301 genotype was performed using a direct sequencing method.Results The rare C allele frequency of TBXA2R+795T〉C was significantly higher in AIA than in ATA (P=0.03) and the TBXA2R+795T〉C polymorphism was also associated with extent of percent fall in forced expiratory volume in 1 s (FEV1) after the inhalation of lysine–acetyl salicylic acid in AIA patients (P=0.009); AIA patients homozygous for the +795 C allele had a greater percent fall of FEV1 compared with individuals with TBXA2R+795 CT or TT genotypes. The frequency of patients carrying both the TBXA2R+795T〉C rare allele and HLA DPB1*0301 was significantly higher in AIA patients (29.4%) than in ATA patients (7.3%) (P=0.008, odds ratio=5.3).Conclusion These results suggest that the polymorphism of TBXA2R+795T〉C may increase bronchoconstrictive response to ASA, which could contribute to the development of the AIA phenotype.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2222.2005.02220.x
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  • 5
    Electronic Resource
    Electronic Resource
    Promoter polymorphism in the 5-lipoxygenase (ALOX5) and 5-lipoxygenase-activating protein (ALOX5AP) genes and asthma susceptibility in a Caucasian population (2003)
    Oxford, UK : Blackwell Science Ltd
    Clinical & experimental allergy 33 (2003), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background 5-Lipoxygenase (5-LO) and 5-lipoxygenase-activating protein (FLAP) are essential for cysteinyl-leukotriene (cys-LT) production, critical mediators in asthma.Objective We sought to identify novel promoter polymorphisms within the FLAP (ALOX5AP) gene promoter and test the role of these and the previously identified 5-LO (ALOX5) Sp1 promoter polymorphism in asthma susceptibility.Methods To assess genetic association with asthma phenotypes, we genotyped 341 Caucasian families (containing two asthmatic siblings) and non-asthmatic control subjects (n=184). Genetic association was determined by case–control and transmission disequilibrium test (TDT) analyses. To determine the functional role of polymorphisms on basal transcription, we generated ALOX5AP-promoter-luciferase constructs and transiently transfected human HeLa cells.Results A novel G/A substitution at –336 bp and a poly(A) repeat (n=19 or 23) at position −169 to −146 bp were identified in the ALOX5AP promoter. Genotyping found the −336 A and poly(A19) alleles at frequencies of q=0.06 and 0.12, respectively. No ALOX5AP allele was associated with asthma or asthma-related phenotypes in case–control or TDT analyses. ALOX5AP-promoter-luciferase analyses did not support a functional role of the −336 or poly(A) polymorphism in determining basal transcription. The ALOX5 Sp1 polymorphism was predominantly homozygous wild-type 5/5 (frequency q=0.70) and heterozygous 4/5 (q=0.23) genotypes and no allele was associated with asthma or asthma-related phenotypes.Conclusion Taken together, these data do not support a significant role for these polymorphisms in genetic susceptibility to asthma in the Caucasian population.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2222.2003.01733.x
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  • 6
    Electronic Resource
    Electronic Resource
    Polymorphisms in the interleukin-4 and interleukin-4 receptor α chain genes confer susceptibility to asthma and atopy in a Caucasian population (2003)
    Oxford, UK : Blackwell Science Ltd
    Clinical & experimental allergy 33 (2003), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background  IL-4 by binding to its receptor (IL-4R) is essential for the development of airway inflammation present in asthma, through the induction of IgE synthesis in B cells and differentiation of T cells to a Th2 phenotype.Objective  To investigate the role of four common polymorphisms in the IL-4 (IL4-34CT and IL4-589CT) and IL-4Rα chain (IL4RAI50V and IL4RAQ576R) genes in conferring susceptibility to the development of atopy and/or asthma.Methods  Two polymorphisms in the IL-4 gene promoter, IL4-34CT and IL4-589CT, and two polymorphisms in the IL-4Rα chain gene, IL4RAI50V and IL4RAQ576R, have been genotyped using PCR-based methods in 341 asthmatic families and in 184 non-asthmatic adults recruited from the south of England.Results  Case–control analysis did not reveal differences in the distribution of the four polymorphisms between asthmatics and controls. However, the transmission disequilibrium test showed that the IL4-589 T allele was preferentially transmitted to asthmatic children (P=0.036) and that the IL4RAQ576 was preferentially transmitted to children with atopic asthma (P=0.018). Haplotype analysis showed a strong association between the IL4-34T/-589T haplotype and asthma per se (P=0.041), and a strong association between the IL4RA I50/Q576 haplotype and atopic asthma (P=0.006).Conclusion  Our data suggest that polymorphisms in the IL-4 and IL-4Rα chain genes might play a role both conferring susceptibility to and modulating severity of atopy and asthma.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2222.2003.01731.x
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  • 7
    Electronic Resource
    Electronic Resource
    ADAM33 polymorphism: association with bronchial hyper-responsiveness in Korean asthmatics (2004)
    Oxford, UK : Blackwell Science Ltd
    Clinical & experimental allergy 34 (2004), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background A disintegrin and metalloprotease 33 (ADAM33) is expressed in the lung by fibroblasts and bronchial smooth muscle cells. Given its structure and cellular provenance, ADAM33 may be associated with airway remodelling and bronchial hyper-responsiveness. Single nucleotide polymorphisms (SNPs) and haplotypes of the ADAM33 gene have previously been associated with asthma susceptibility in the Caucasian population.Objective and Methods To assess whether genetic variants of ADAM33 are related to asthma in a Korean population, we conducted an association study of the ADAM33 gene with asthma susceptibility, bronchial hyper-reactivity and serum IgE in Korean asthmatics (n=326) and normal controls (n=151). Five of the 14 polymorphisms originally reported to be associated with asthma development (S1 G〉A, T1 T〉C, V-1 C〉A, V1 T〉A, V4 C〉G) were genotyped using single base extension and electrophoresis. Haplotypes and their frequencies were inferred using the algorithm implemented by the software Arlequin. Allele frequencies of each SNP and haplotypes were compared between the patients and the normal controls using logistic regression analysis.Results There was no significant difference in the distribution of SNPs and the six haplotypes between asthmatics and normal controls. All single SNPs and six haplotypes in ADAM33 were also analysed for the association with level of PC20 using general linear models. The distribution of the T1 T〉C SNP and one haplotype (ht4: GCGG) showed significant association with log-transformed PC20 methacholine level in the asthma patients (P=0.03 and 0.0007, respectively, using a co-dominant model).Conclusion Polymorphism of ADAM33 may contribute to development of BHR in asthma.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2222.2004.01977.x
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  • 8
    Electronic Resource
    Electronic Resource
    Polymorphism of tandem repeat in promoter of 5-lipoxygenase in ASA-intolerant asthma: a positive association with airway hyperresponsiveness (2005)
    Oxford, UK : Munksgaard International Publishers
    Allergy 60 (2005), S. 0 
    Details
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background:  5-Lipooxygenase (ALOX5) and 5-lipoxygenase-activating protein (ALOX5AP) are known as key enzymes in cysteinyl-leukotriene (cys-LT) production, critical mediators in aspirin acetylsalicyclic acid (ASA)-intolerant asthma (AIA). To date, studies of the promoter region of ALOX5 gene has revealed the potential influence of a variable number of tandem repeats of a Sp1- and Egr1-binding motif, on the transcription rate.Methods:  To understand the pathological process that arises from cys-LT overproduction in AIA, we genotyped ALOX5 Sp1 and ALOX5AP poly(A) repeat promoter polymorphism by fluorescent-based capillary electrophoresis in the Korean population.Results:  No significant differences in allele and genotype frequencies of the ALOX5 and ALOX5AP promoter polymorphisms were observed between the three groups. However, there was a strong association of the ALOX5 Sp1 repeat polymorphism with airway hyperresponsiveness (AHR; PC20 methacholine); AIA patients carrying a mutant allele (n 〉 5 or n 〈 5 repeats) showed increased AHR compared to AIA patients with wild-type genotype (P = 0.003).Conclusion:  Although the alleles of the ALOX5 and ALOX5AP promoter cannot be considered as a prominent risk factor in the development of AIA, the genetic variant of tandem repeat (GGGCGG; Sp1-binding motif) in ALOX5 promoter is associated with the severity of airway hyperresponsiveness in AIA patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1398-9995.2005.00780.x
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  • 9
    Electronic Resource
    Electronic Resource
    Lack of association of HLA class I genes and TNF α-308 polymorphism in toluene diisocyanate-induced asthma (2004)
    Oxford, UK : Munksgaard International Publishers
    Allergy 59 (2004), S. 0 
    Details
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background:  Toluene diisocyanate (TDI)-induced asthma is a common cause of occupational asthma and it affects 5–15% of the exposed population suggesting an underlying genetic susceptibility.Methods:  To investigate the role of genetic factors in the development of TDI-induced asthma, we analyzed the distribution of human leukocyte antigen (HLA) class I genes and of tumor necrosis factor (TNF)-α A-308G polymorphism in 142 patients with TDI-induced asthma and in 50 asymptomatic exposed subjects.Results:  Neither the distribution of HLA class I antigens nor the distribution of TNF-α A-308G polymorphism was different between patients with TDI-induced asthma and asymptomatic exposed subjects.Conclusions:  These results suggest that HLA class I antigens and TNF-α A-308G are not associated with susceptibility or resistance to the development of TDI-induced asthma.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1398-9995.2003.00352.x
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