However, in stratification analyses of age, BMI, and forced expiratory volume in 1 s (FEV1)/FEV, we failed to find any association between <i>HIF1A</i> gene rs10873142 polymorphism with COPD risk.
In interpreting this interaction, we showed that the genetic risk of falling below the FEV /FVC threshold used to diagnose chronic obstructive pulmonary disease is higher among ever smokers than among never smokers.
The SFTPB exon polymorphism rs1130866 significantly protected subjects from COPD (adjusted P = 0.004) and was associated with an increase in forced expiratory volume in 1 s (FEV(1)) (adjusted P = 0.014).
Four SNPs (rs1964678, rs12593229, rs965604 and rs13180) in IREB2 were associated with forced expiratory volume in 1 s (FEV(1))% predicted and three SNPs (rs16969968, rs8034191 and rs1051730) in CHRNA3/5 were both associated with FEV(1)% predicted and FEV(1)/FVC in COPD cases (P range 0.007-0.050).
This SNP was also associated with a lower FEV(1) % predicted (57.2 ± 1.8 for TT vs 50.8 ± 2.3 for TA/AA, P = 0.03) and DL(CO) /V(A) (2.89 ± 0.1 in TT vs 2.53 ± 0.14 in TA/AA, P = 0.036) in COPD patients.
Interestingly, our observations include significant, replicable associations between SERPINA1 hypomethylation and COPD and lower average lung function phenotypes (combined P values: COPD, 1.5 × 10(-23); FEV(1)/FVC, 1.5 × 10(-35); FEV(1), 2.2 × 10(-40)).
Genotyping this single nucleotide polymorphism (SNP) and another nearby SNP in linkage disequilibrium (rs2604894) in 2859 subjects from the family-based International COPD Genetics Network study (ICGN) demonstrated supportive evidence for association for COPD (P = 0.28 and 0.11 for rs7937 and rs2604894), pre-bronchodilator FEV(1) (P = 0.08 and 0.04) and severe (GOLD 3&4) COPD (P = 0.09 and 0.017).
We studied all tagging SNPs in TLR2 and TLR4 and their associations with the level and change over time of both FEV(1) and sputum inflammatory cells in moderate-to-severe COPD.
We explored the association of these polymorphisms to three COPD phenotypes: a COPD binary phenotype and two quantitative traits (post-bronchodilator forced expiratory volume in 1 s (FEV₁) % predicted and FEV₁/forced vital capacity (FVC)).
In the family-based analysis of the Boston Early-Onset COPD Study, rs911887 was associated with prebronchodilator and postbronchodilator FEV(1) (P = 0.003 and P = 0.02, respectively).
Furthermore, compared with controls, expression levels of PPARgamma, PGC-1alpha, and gamma-GCS significantly increased in the lungs of mild COPD patients, and progressively decreased in lungs of patients with moderate and severe COPD. gamma-GCS protein was positively correlated with FEV(1)%.
Patients with polymorphism had more chronic bronchitis, a lower body mass index, and a greater annual decline in FEV(1) than patients with COPD without rs361525 polymorphism.
Two SNPs in TGFB1 (C to T substitution at nucleotide -509 and substitution of leucine 10 with proline (Leu10Pro)), Leu50Val in SFTPA1 and Ala160Thr in SFTPD showed evidence suggestive of association with FEV(1)/IVC in subjects with GOLD stage >or=2 COPD.
Within the Normative Aging Study (NAS), a cohort of initially healthy adult men, we tested for an association between SNPs that were associated with FEV(1) and the time to the onset of COPD.