Additional file 2: Table S1–Table S6. of Lung function associated gene Integrator Complex subunit 12 regulates protein synthesis pathways

Contains all supplemental table data. Each table has its legend. (PDF 166 kb

Meta-analysis of genome-wide linkage studies of asthma and related traits-0

Test response. A p(SR) of p < 0.000417 = significant linkage, p < 0.0083 = suggestive linkage. p(SR) & p(OR) data were transformed using f(x) = 0.05/x and plotted on a logscale to improve clarity.<p><b>Copyright information:</b></p><p>Taken from "Meta-analysis of genome-wide linkage studies of asthma and related traits"</p><p>http://respiratory-research.com/content/9/1/38</p><p>Respiratory Research 2008;9(1):38-38.</p><p>Published online 28 Apr 2008</p><p>PMCID:PMC2391165.</p><p></p

Meta-analysis of genome-wide linkage studies of asthma and related traits-1

Test response. A p(SR) of p < 0.000417 = significant linkage, p < 0.0083 = suggestive linkage. p(SR) & p(OR) data were transformed using f(x) = 0.05/x and plotted on a logscale to improve clarity.<p><b>Copyright information:</b></p><p>Taken from "Meta-analysis of genome-wide linkage studies of asthma and related traits"</p><p>http://respiratory-research.com/content/9/1/38</p><p>Respiratory Research 2008;9(1):38-38.</p><p>Published online 28 Apr 2008</p><p>PMCID:PMC2391165.</p><p></p

Collapsing methods results for most significant loci in stage 2.

<p>Collapsing methods results for most significant loci in stage 2.</p

Effect of salmeterol or cytokine treatment for 4 hours on promoter activity in Human ASM cells transfected with -Luciferase or control constructs

<p><b>Copyright information:</b></p><p>Taken from "Salmeterol and cytokines modulate inositol-phosphate signalling in Human airway smooth muscle cells via regulation at the receptor locus"</p><p>Respiratory Research 2007;8(1):68-68.</p><p>Published online 28 Sep 2007</p><p>PMCID:PMC2117012.</p><p></p> Complete medium was replaced with serum free medium and cells were transfected with 0.12 μg of pGL4-Luc2 using Fugene 6 (Roche) at a 3:1 ratio (Fugene:DNA). For derivatives of pGL4-Luc2 containing the HRH1 or SV40 control inserts equimolar amounts of DNA were used. Cells were allowed to grow for 16 hours prior to the addition of medium alone, 10 ng/ml TNFα, 10 ng/ml IFNγ, 50 ng/ml IL-13 or 1 μM salmeterol. Following 4 hours treatment cells were harvested and firefly luciferase was quantified. pGL4-Luc2 (A), pGL4-SV40-Luc2 (B), pGL4-HRH1-1 kb-Luc2 (C), pGL4-HRH1-2 kb-Luc2 (D), pGL4-HRH1-3 kb-Luc2 (E), pGL4-HRH1-4 kb-Luc2 (F) transfections. Data is normalised to the mean luciferase activity of each construct transfection treated with medium alone +/- S.E.M. (n = 4 independent experiments). Dunnett's Multiple Comparison Test (*p < 0.05)

Flow chart of the variant selection process.

<p>Flow chart of the variant selection process.</p

Effect of salmeterol or cytokine treatment for 4 hours on promoter activity in Human ASM cells transfected with -Luciferase constructs

<p><b>Copyright information:</b></p><p>Taken from "Salmeterol and cytokines modulate inositol-phosphate signalling in Human airway smooth muscle cells via regulation at the receptor locus"</p><p>Respiratory Research 2007;8(1):68-68.</p><p>Published online 28 Sep 2007</p><p>PMCID:PMC2117012.</p><p></p> Human ASM cells were transfected and stimulated as described in Figure 4 except derivatives of pGL4-Luc2 containing the BDKRB2 inserts were used. Following 4 hours treatment cells were harvested and firefly luciferase was quantified. pGL4-BDKRB2-1kb-Luc2 (A), pGL4-BDKRB2-2kb-Luc2 (B), pGL4-BDKRB2-3kb-Luc2 (C), pGL4-BDKRB2-4kb-Luc2 (D) transfections. Data is normalised to the mean luciferase activity of each construct transfection treated with medium alone +/- S.E.M. (n = 4 independent experiments). Dunnett's Multiple Copmarison Test (**p < 0.01)

COPD association results in stage 1 and 2 for lung function sentinel variants analysed in stage 2.

<p>COPD association results in stage 1 and 2 for lung function sentinel variants analysed in stage 2.</p

Effect of salmeterol or cytokine treatment on H1 Histamine Receptor and B2 Bradykinin Receptor mRNA expression in Human ASM

<p><b>Copyright information:</b></p><p>Taken from "Salmeterol and cytokines modulate inositol-phosphate signalling in Human airway smooth muscle cells via regulation at the receptor locus"</p><p>Respiratory Research 2007;8(1):68-68.</p><p>Published online 28 Sep 2007</p><p>PMCID:PMC2117012.</p><p></p> ASM cells were serum starved for 24 hours and then treated with medium alone, 10 ng/ml TNFα, 10 ng/ml IFNγ, 50 ng/ml IL-13 or 1 μM salmeterol for 4 or 24 hours. mRNA levels of the H1 Histamine Receptor and B2 Bradykinin Receptor were quantified using Real Time PCR and normalised using the 18s ribosomal RNA endogenous control. HRH1 mRNA quantification following 4 hours (A) and 24 hours (B) stimulation. BDKRB2 mRNA quantification following 4 hours (C) and 24 hours (D) stimulation. Data is normalised to medium control = 100%, n = 3 independent experiments in triplicate, mean +/- S.E.M. Dunnett's Multiple Comparison Test (*p < 0.05)

PLAUR polymorphisms and lung function in UK smokers

Background: We 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. Methods: 25 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 (FEV[subscript 1], FEV[subscript 1]/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. Results: Five SNPs showed a significant association (p < 0.01) with baseline lung function; rs2302524(Lys220Arg) and rs2283628(intron 3) were associated with lower and higher FEV[subscript 1] respectively. rs740587(-22346), rs11668247(-20040) and rs344779(-3666) in the 5'region were associated with increased FEV[subscript 1]/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. Conclusion: This 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