Assessing the Validity of Asthma Associations for Eight Candidate Genes and Age at Diagnosis Effects
PLOS ONE
Authors: Pino-Yanes, Maria; Corrales, Almudena; Cumplido, Jose; Poza, Paloma; Sanchez-Machin, Inmaculada; Sanchez-Palacios, Anselmo; Figueroa, Javier; Acosta-Fernandez, Orlando; Buset, Nisa; Carlos Garcia-Robaina, Jose; Hernandez, Mariano; Villar, Jesus; Carrillo, Teresa; Flores, Carlos
Abstract
Background: Before the advent of genome-wide association studies (GWAS), ADAM33, ADRB2, CD14, MS4A2 (alias FCER1B), IL13, IL4, IL4R, and TNF constituted the most replicated non-HLA candidate genes with asthma and related traits. However, except for the IL13-IL4 region, none of these genes have been found in close proximity of genome-wide significant hits among GWAS for asthma or related traits. Here we aimed to assess the reproducibility of these asthma associations and to test if associations were more evident considering the effect of age at diagnosis. Methodology/Principal Findings: We systematically evaluated 286 common single nucleotide polymorphisms (SNPs) of these 8 genes in a sample of 1,865 unrelated Spanish individuals (606 asthmatics and 1,259 controls). We found that variants at MS4A2, IL4R and ADAM33 genes demonstrated varying association effects with the age at diagnosis of asthma, with 10 SNPs showing study-wise significance after the multiple comparison adjustment. In addition, in silico replication with GWAS data supported the association of IL4R. Conclusions/Significance: Our results support the important role of MS4A2, IL4R and ADAM33 genes in asthma and/or atopy susceptibility. However, additional studies in larger samples sets are needed to firmly implicate these genes in asthma susceptibility, and also to identify the causal variation underlying the associations found.
An investigation of the association between ADRB2 gene polymorphisms and asthma in Kazakh population
CLINICAL RESPIRATORY JOURNAL
Authors: Akparova, Almira; Aripova, Akmaral; Abishev, Meirzhan; Kazhiyakhmetova, Baglan; Pirmanova, Ainur; Bersimbaev, Rakhmetkazhi
Abstract
Introduction Beta-2-adrenergic receptor (ADRB2) is present in the cells of the respiratory tract, including bronchial smooth muscle cells and bronchial epithelium, and is a target for endogenous catecholamines and drugs used to treat the obstructive lung diseases. Objectives This study aimed to investigate the possible association of the Arg16Gly and Gln27Glu polymorphisms of the ADRB2 gene with asthma and its endophenotypes in the Kazakh population. Methods A total of 70 asthmatic patients and 80 healthy controls were genotyped for Arg16Gly and Gln27Glu polymorphisms of the ADRB2 gene by using quantitative real-time polymerase chain reaction. Statistical analysis was performed with the Graph Pad InStat 7 Software. Results No associations between the asthma patients and healthy individuals were found when the allele and genotype distribution of Arg16Gly and Gln27Glu single nucleotide polymorphisms were compared. Analysis of the haplotype frequencies showed statistically significant differences between patients with asthma and controls for Arg16Gly/Gln27Gln and Arg16Gly/Gln27Glu haplotypes (odds ratio [OR] = 2.12, 95% confidence interval [CI] = 0.87-5.16 and OR = 2.25, 95% CI = 0.89-5.67 respectively). The Arg16 allele and Arg16Arg genotype frequencies were higher in patients with uncontrolled asthma than in controls (chi(2) = 5.17, df = 1, P = 0.02 and chi(2) = 5.36, df = 1, P = 0.02 respectively). Conclusion The results of this study support the possible involvement of Arg16Gly polymorphism in the development of uncontrolled asthma, and indicate that Arg16Gly/Gln27Gln and Arg16Gly/Gln27Glu haplotypes are more common in asthma patients in the Kazakh population.