BACKGROUND: The specific genetic contributions to childhood asthma have been difficult to elucidate. A recent whole-genome association study suggested that single nucleotide polymorphisms at loci controlling the expression of the ORMDL3 gene and others in the neighborhood of the NRG1 and ERO1LB genes might be important. OBJECTIVE: We sought to replicate the associations of these genetic markers with asthma in a large population of asthmatic patients from Scotland and to assess the effect of these variants on asthma outcomes. METHODS: Using mouthwash-derived DNA and clinical interviews and measurements, we investigated the association of 3 single nucleotide polymorphisms in the candidate genes with susceptibility to asthma in a case-control study and also exacerbations in a group of 1054 patients aged 3 to 22 years. RESULTS: A common C/T polymorphism at a locus controlling ORMDL3 gene expression (rs7216389) was significantly associated with the risk of childhood asthma (P = 1.73 x 10(-12)), with a single copy of the T allele conferring an odds ratio of 1.50 (95% CI, 1.24-1.81) and 2 copies of the T allele conferring an odds ratio of 2.11 (95% CI, 1.71-2.61), respectively. In asthmatic patients the T allele was associated with exacerbations of the condition (P = .008). Polymorphisms at the loci of nearby genes for NRG1 (rs4512342) and ERO1LB (rs10924993) were associated with neither the occurrence of nor exacerbations of asthma. CONCLUSION: A common genetic variation at a locus controlling the expression of the ORMDL3 locus increases the susceptibility to asthma and is associated with poor control of the condition in children and young adults.
BACKGROUND: The specific genetic contributions to childhood asthma have been difficult to elucidate. A recent whole-genome association study suggested that single nucleotide polymorphisms at loci controlling the expression of the ORMDL3 gene and others in the neighborhood of the NRG1 and ERO1LB genes might be important. OBJECTIVE: We sought to replicate the associations of these genetic markers with asthma in a large population of asthmatic patients from Scotland and to assess the effect of these variants on asthma outcomes. METHODS: Using mouthwash-derived DNA and clinical interviews and measurements, we investigated the association of 3 single nucleotide polymorphisms in the candidate genes with susceptibility to asthma in a case-control study and also exacerbations in a group of 1054 patients aged 3 to 22 years. RESULTS: A common C/T polymorphism at a locus controlling ORMDL3 gene expression (rs7216389) was significantly associated with the risk of childhood asthma (P = 1.73 x 10(-12)), with a single copy of the T allele conferring an odds ratio of 1.50 (95% CI, 1.24-1.81) and 2 copies of the T allele conferring an odds ratio of 2.11 (95% CI, 1.71-2.61), respectively. In asthmatic patients the T allele was associated with exacerbations of the condition (P = .008). Polymorphisms at the loci of nearby genes for NRG1 (rs4512342) and ERO1LB (rs10924993) were associated with neither the occurrence of nor exacerbations of asthma. CONCLUSION: A common genetic variation at a locus controlling the expression of the ORMDL3 locus increases the susceptibility to asthma and is associated with poor control of the condition in children and young adults.
Authors: Eva Halapi; Daniel F Gudbjartsson; Gudrun M Jonsdottir; Unnur S Bjornsdottir; Gudmar Thorleifsson; Hafdis Helgadottir; Carolyn Williams; Gerard H Koppelman; Andrea Heinzmann; H Marike Boezen; Aslaug Jonasdottir; Thorarinn Blondal; Sigurjon A Gudjonsson; Adalbjorg Jonasdottir; Theodora Thorlacius; Amanda P Henry; Janine Altmueller; Marcus Krueger; Hyoung Doo Shin; Soo-Taek Uh; Hyun Sub Cheong; Brynja Jonsdottir; Bjorn R Ludviksson; Dora Ludviksdottir; David Gislason; Choon-Sik Park; Klaus Deichmann; Philip J Thompson; Matthias Wjst; Ian P Hall; Dirkje S Postma; Thorarinn Gislason; Augustine Kong; Ingileif Jonsdottir; Unnur Thorsteinsdottir; Kari Stefansson Journal: Eur J Hum Genet Date: 2010-04-07 Impact factor: 4.246
Authors: Sara E Dobbins; Fay J Hosking; Sanjay Shete; Georgina Armstrong; Anthony Swerdlow; Yanhong Liu; Robert Yu; Ching Lau; Minouk J Schoemaker; Sarah J Hepworth; Kenneth Muir; Melissa Bondy; Richard S Houlston Journal: Int J Cancer Date: 2010-05-25 Impact factor: 7.396
Authors: Denise Daley; Mathieu Lemire; Loubna Akhabir; Moira Chan-Yeung; Jian Qing He; Treena McDonald; Andrew Sandford; Dorota Stefanowicz; Ben Tripp; David Zamar; Yohan Bosse; Vincent Ferretti; Alexandre Montpetit; Marie-Catherine Tessier; Allan Becker; Anita L Kozyrskyj; John Beilby; Pamela A McCaskie; Bill Musk; Nicole Warrington; Alan James; Catherine Laprise; Lyle J Palmer; Peter D Paré; Thomas J Hudson Journal: Hum Genet Date: 2009-02-27 Impact factor: 4.132
Authors: David K Breslow; Sean R Collins; Bernd Bodenmiller; Ruedi Aebersold; Kai Simons; Andrej Shevchenko; Christer S Ejsing; Jonathan S Weissman Journal: Nature Date: 2010-02-25 Impact factor: 49.962