Association between β2-Adrenoceptor Gene Polymorphisms and Asthma Risk: An Updated Meta-Analysis

<div><p>Background</p><p>Evidence is increasingly accumulated about multiple roles for the β2-adrenoceptor gene in asthma. The results were inconsistent partly due to small sample sizes. To assess the association between β2-adrenoceptor gene polymorphisms and asthma risk, a meta-analysis was performed.</p><p>Methods</p><p>We comprehensively searched the PubMed, EMBASE, BIOSIS Previews databases and extracted data from all eligible articles to estimate the association between β2-adrenoceptor gene polymorphisms and asthma risk. The pooled odds ratio (OR) with 95% confidence intervals (CIs) were calculated.</p><p>Results</p><p>Thirty-seven studies involving 6648 asthma patients and 15943 controls were included in the meta-analysis. Overall, significant associations were found in allelic genetic model (OR = 1.06, 95% CI = 1.01∼1.12), recessive genetic model (OR = 1.11, 95% CI = 1.02∼1.21) for Arg/Gly16. Stratified by ethnicity and age, significant associations were also found in Asian population in allelic genetic model, recessive genetic model and addictive model. For Gln/Glu27, no significant association was found when we combined all eligible studies. Age stratification showed significant associations in adults in allelic genetic model and recessive genetic model, but no significant association was found among Asians and Caucasians in ethnicity stratification.</p><p>Conclusions</p><p>This meta-analysis implied that the β2-adrenoceptor Arg/Gly16 polymorphism was likely to contribute to asthma risk in Asian population. Gln/Glu27 polymorphism might be a contributor to asthma susceptibility for adults.</p></div

Galbraith plots of the association between β2AR Arg16Gly polymorphism and asthma.

<p>A) Asian population subgroup; B) caucasian population subgroup. Four studies# maybe the main contributors to the heterogeneity Asian population subgroup; One studies# maybe the main contributors to the heterogeneity Asian population subgroup.</p

Results of the pooled analyses and subgroup analyses for the β2AR Gln/Glu27 polymorphism and asthma risk.

<p># Pooled result not included study of Santilan, A A#, n, number of studies.</p

Funnel plot of publication bias for β2AR polymorphism under recessive genetic model.

<p>A) Arg/Gly16; B) Gln/Glu27. Funnel plot with pseudo 95% confidence limits was used.</p

Results of the pooled analyses and subgroup analyses for the β2AR Arg/Gly16 polymorphism and asthma risk.

<p>n, number of studies.</p

Flow Diagram for Inclusion of Studies in Meta-analysis.

<p>The initial search identified 2205 articles, of which, 37 were included in the final analysis.</p

Characteristics of studies included in meta-analysis.

<p>NA, not available; PCR, polymerase chain reaction; RFLP, restricted fragment length polymorphisms; SSP, sequence.</p><p>-specific primers; SPT, skin prick test; BHR,bronchial hyperresponsiveness; TDI, toluene diisocyanate; ARMS, amplification refractory mutation system;Mixed, participants involved children and adults.</p

DataSheet_1_Ankylosing spondylitis: acute/subacute vs. chronic iridocyclitis - a bidirectional two-sample Mendelian randomization study.docx

BackgroundObservational studies found associations between ankylosing spondylitis (AS) and iridocyclitis (IC), but the causality remained unconfirmed.MethodsWe employed two-sample Mendelian randomization (MR) to investigate the bidirectional causal relationships between AS and IC. Single-nucleotide polymorphisms (SNPs) were chosen from the FinnGen database’s genome-wide association studies (GWAS) following a rigorous evaluation of the studies’ quality. Sensitivity analysis was performed to assess the potential influence of pleiotropy and heterogeneity on the MR findings.ResultsElevated genetic risk for AS showed positive causal effects on IC and its subtypes (IC, OR = 1.094, 95% CI = 1.035-1.157, P = 0.00156; Acute/Subacute IC, OR = 1.327, 95% CI = 1.266-1.392, P = 8.73×10-32; Chronic IC, OR = 1.454, 95% CI = 1.308-1.618, P = 5.19×10-12). Significant causal association was specifically observed between Acute/Subacute IC and AS (OR = 1.944, 95% CI = 1.316-2.873, P = 8.38×10-4). Sensitivity analysis suggested that horizontal pleiotropy was unlikely to influence the causality, and the leave-one-out analysis confirmed that a single SNP did not drive the observed associations.ConclusionOur findings provide new proof of a positive causal relationship between AS and IC in the European population. Notably, it is Acute/Subacute IC, rather than IC as a whole or Chronic IC, that is associated with an elevated risk of AS. These results emphasize the significance of considering AS characteristics in the diagnosis of Acute/Subacute IC.</p

Effect of MCF-7 preconditioned media on HUVEC tube formation and invasion.

<p>(A and B) The tube formation assay was performed as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0032368#s4" target="_blank">Materials and Methods</a>s. HUVECs were plated on Matrigel and incubated under hypoxia for 6 h. Tube lengths were measured with Image-Pro Plus software; the histograms represent the quantification of the tube length of HUVECs. (C and D) The invasion assay was performed as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0032368#s4" target="_blank">Materials and Methods</a>. After 4 h under hypoxia, the amount of invaded cells was calculated in five random high-power fields (400×), and the number from the control group was used as a control. The histogram represents the quantification of cells that invaded. The data are the mean ± standard deviation (SD) for three independent experiments. Statistical significance was assessed using one-way ANOVA and Student's <i>t</i>-test. * or ** indicates <i>P</i><0.05 or <i>P</i><0.01, respectively, when compared with the control.</p

Effect of MCF-7 preconditioned media on HUVEC proliferation.

<p>(A) HUVECs were grown to confluence and were then cultured in preconditioned media (derived from MCF-7 and Ad-LacZ-MCF-7 cells pretreated under normoxia and hypoxia for 24 or 48 h) for 24 h, and serum-free DMEM was used as a control. (B) HUVECs were grown to confluence and were then cultured in preconditioned media (derived from Ad-LacZ-MCF-7 or Ad-<i>NDRG2</i>-MCF-7 cells pretreated under normoxia and hypoxia for 24 or 48 h) for 24 h. Ad-LacZ -MCF-7(N) or Ad-LacZ-MCF-7 (H) was used as controls. N, normoxia; H, hypoxia. The data are the mean ± standard deviation (SD) for three independent experiments. Statistical significance was assessed using one-way ANOVA and Student's <i>t</i>-test. * or ** indicates <i>P</i><0.05 or <i>P</i><0.01, respectively, when compared with the control.</p