Genetics of Asthma: What's New?

Sayers, Ian; Beghè, Bianca; Holloway, John W.; Holgate, S. T.

doi:10.1002/9780470693889.ch9

Cited by 5 publications

(4 citation statements)

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“…In conclusion, asthma is a multifactorial disease with a complex genetic and environmental basis. Multiple studies have reported both positive and negative associations for a wide variety of candidate genes/polymorphisms, including IL‐4, IL‐13 and the β‐chain of the high‐affinity IgE receptor (FcɛRI), further confounding conclusions and supporting the need for the publication of negative genetic association data to avoid bias in the literature [1]. The polymorphisms described in the ALOX5AP and ALOX5 gene promoters require analysis in cohorts of greater disease severity and ethnic diversity before final conclusions can be made, but the present study indicates that these polymorphisms do not constitute genetic risk factors for the development of asthma in the Caucasian population.…”

Section: Discussionmentioning

confidence: 99%

“…Asthma is a complex multifactorial disease, with both strong genetic and environmental components leading to the expression of disease [1]. The cysteinyl‐leukotrienes (cys‐LTs) are lipid mediators that play a significant role in bronchoconstriction and airway inflammation, and drugs that target these mediators have clinical efficacy in asthma [2, 3].…”

Section: Introductionmentioning

confidence: 99%

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Promoter polymorphism in the 5‐lipoxygenase (ALOX5) and 5‐lipoxygenase‐activating protein (ALOX5AP) genes and asthma susceptibility in a Caucasian population

Sayers¹,

Barton

Rorke

et al. 2003

Clin Experimental Allergy

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Promoter polymorphism in the 5‐lipoxygenase (ALOX5) and 5‐lipoxygenase‐activating protein (ALOX5AP) genes and asthma susceptibility in a Caucasian population

Sayers¹,

Barton

Rorke

et al. 2003

Clin Experimental Allergy

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“…Chronic Obstructive Pulmonary Disease (COPD) and asthma are complex respiratory diseases involving both genetic and environmental factors ( e.g . smoking exposure in COPD, allergen exposure in asthma) [ 1 , 2 ]. Using 587 asthma families we have recently fine mapped a 14.4 Mb region on Chromosome 19q13 and identified the urokinase plasminogen activator receptor ( PLAUR , plasminogen activator receptor, urokinase type, alternative symbols; UPAR and CD87 ) gene as an asthma susceptibility gene [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

PLAURpolymorphisms and lung function in UK smokers

et al. 2009

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BackgroundWe have previously identified Urokinase Plasminogen Activator Receptor (PLAUR) as an asthma susceptibility gene. In the current study we tested the hypothesis that PLAUR single nucleotide polymorphisms (SNPs) determine baseline lung function and contribute to the development of Chronic Obstructive Pulmonary Disease (COPD) in smokers.Methods25 PLAUR SNPs were genotyped in COPD subjects and individuals with smoking history (n = 992). Linear regression was used to determine the effects of polymorphism on baseline lung function (FEV1, FEV1/FVC) in all smokers. Genotype frequencies were compared in spirometry defined smoking controls (n = 176) versus COPD cases (n = 599) and COPD severity (GOLD stratification) using logistic regression.ResultsFive SNPs showed a significant association (p < 0.01) with baseline lung function; rs2302524(Lys220Arg) and rs2283628(intron 3) were associated with lower and higher FEV1 respectively. rs740587(-22346), rs11668247(-20040) and rs344779(-3666) in the 5'region were associated with increased FEV1/FVC ratio. rs740587 was also protective for COPD susceptibility and rs11668247 was protective for COPD severity although no allele dose relationship was apparent. Interestingly, several of these associations were driven by male smokers not females.ConclusionThis study provides tentative evidence that the asthma associated gene PLAUR also influences baseline lung function in smokers. However the case-control analyses do not support the conclusion that PLAUR is a major COPD susceptibility gene in smokers. PLAUR is a key serine protease receptor involved in the generation of plasmin and has been implicated in airway remodelling.

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“…1,2 There is extensive evidence that chromosome 19q13 contains genes predisposing to asthma or asthma-related phenotypes [3][4][5][6][7][8][9] (see this article's Table E1 in the Online Repository at www.jacionline.org). Within the 19q13.1-13.3 region, there appear to be 2 clusters of linkage to asthma-related phenotypes: markers D19S198/D19S900/ D19S178 highlight a 2.3-centimorgans (cM) (2.25-Mbp) region [3][4][5]8 (region 1), and markers D19S601/D19S571/D19S180 highlight a 4.5-cM (1.15-Mbp) region 6,7,10 (region 2).…”

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confidence: 99%