BACKGROUND: Recent studies demonstrate that genetic variations in the human beta(2)-adrenergic receptor (beta(2)AR) structure at codons 16 and 27 alter receptor function in vitro and are associated with asthma severity and airway hyperresponsiveness but have not been linked to asthma diagnosis. The nature of the relation in a more homogeneous population is uncertain. OBJECTIVE: We determined frequencies of these polymorphisms to explore the association between beta(2)AR haplotypes and asthma diagnosis and phenotype. METHODS: This is a population-based, case-control study that involves a total sample of 907 unrelated Mexican Mestizos. Genotyping at beta(2)AR was identified by polymerase chain reaction-restriction fragment length polymorphism analysis. Multivariate logistic regression analysis was used to estimate the odds ratio (OR) of the association between beta(2)AR haplotype status and asthma diagnosis. RESULTS: A significant inverse association was found between subjects with Glu27 allele (OR, 0.5; 95% CI, 0.4 to 0.7) and Gly16-Glu27 alleles (OR, 0.5; 95% CI, 0.3 to 0.8) and asthma. Sex differences in this association were explored, given the complex relation between sex and asthma. Among men, a positive association was present between the "Gly16 allele without Glu27" (OR, 2.9; 95% CI, 1.26 to 6.8) and asthma. In contrast, a lower risk of asthma was found among women Gly16-Glu27 alleles (OR, 0.3; 95% CI, 0.2 to 0.6). Nocturnal asthma was associated with the Gly16 allele (OR, 1.8; 95% CI, 1.3 to 2.6). CONCLUSIONS: Variation in the beta(2)AR gene is associated in the pathogenesis of asthma and acts as a disease modifier in nocturnal asthma.
BACKGROUND: Recent studies demonstrate that genetic variations in the humanbeta(2)-adrenergic receptor (beta(2)AR) structure at codons 16 and 27 alter receptor function in vitro and are associated with asthma severity and airway hyperresponsiveness but have not been linked to asthma diagnosis. The nature of the relation in a more homogeneous population is uncertain. OBJECTIVE: We determined frequencies of these polymorphisms to explore the association between beta(2)AR haplotypes and asthma diagnosis and phenotype. METHODS: This is a population-based, case-control study that involves a total sample of 907 unrelated Mexican Mestizos. Genotyping at beta(2)AR was identified by polymerase chain reaction-restriction fragment length polymorphism analysis. Multivariate logistic regression analysis was used to estimate the odds ratio (OR) of the association between beta(2)AR haplotype status and asthma diagnosis. RESULTS: A significant inverse association was found between subjects with Glu27 allele (OR, 0.5; 95% CI, 0.4 to 0.7) and Gly16-Glu27 alleles (OR, 0.5; 95% CI, 0.3 to 0.8) and asthma. Sex differences in this association were explored, given the complex relation between sex and asthma. Among men, a positive association was present between the "Gly16 allele without Glu27" (OR, 2.9; 95% CI, 1.26 to 6.8) and asthma. In contrast, a lower risk of asthma was found among womenGly16-Glu27 alleles (OR, 0.3; 95% CI, 0.2 to 0.6). Nocturnal asthma was associated with the Gly16 allele (OR, 1.8; 95% CI, 1.3 to 2.6). CONCLUSIONS: Variation in the beta(2)AR gene is associated in the pathogenesis of asthma and acts as a disease modifier in nocturnal asthma.
Authors: Gregory A Hawkins; Kelan Tantisira; Deborah A Meyers; Elizabeth J Ampleford; Wendy C Moore; Barbara Klanderman; Stephen B Liggett; Stephen P Peters; Scott T Weiss; Eugene R Bleecker Journal: Am J Respir Crit Care Med Date: 2006-08-24 Impact factor: 21.405
Authors: Dagan A Loisel; Zheng Tan; Christopher J Tisler; Michael D Evans; Ronald E Gangnon; Daniel J Jackson; James E Gern; Robert F Lemanske; Carole Ober Journal: J Allergy Clin Immunol Date: 2011-07-27 Impact factor: 10.793
Authors: Rachel A Myers; Nicole M Scott; W James Gauderman; Weiliang Qiu; Rasika A Mathias; Isabelle Romieu; Albert M Levin; Maria Pino-Yanes; Penelope E Graves; Albino Barraza Villarreal; Terri H Beaty; Vincent J Carey; Damien C Croteau-Chonka; Blanca del Rio Navarro; Christopher Edlund; Leticia Hernandez-Cadena; Efrain Navarro-Olivos; Badri Padhukasahasram; Muhammad T Salam; Dara G Torgerson; David J Van den Berg; Hita Vora; Eugene R Bleecker; Deborah A Meyers; L Keoki Williams; Fernando D Martinez; Esteban G Burchard; Kathleen C Barnes; Frank D Gilliland; Scott T Weiss; Stephanie J London; Benjamin A Raby; Carole Ober; Dan L Nicolae Journal: Hum Mol Genet Date: 2014-05-13 Impact factor: 6.150