Polymorphisms in signal transducer and activator of transcription 3 and lung function in asthma

• Main Authors: Lazarus Ross, Lake Stephen, Tantisira Kelan G, Litonjua Augusto A, Richter Brent G, Gabriel Stacey, Silverman Eric S, Weiss Scott T
• Format: Article
• Language: English
• Published: BMC 2005-06-01
• Series: Respiratory Research
• Online Access: http://respiratory-research.com/content/6/1/52

<p>Abstract</p> <p>Background</p> <p>Identifying genetic determinants for lung function is important in providing insight into the pathophysiology of asthma. Signal transducer and activator of transcription 3 is a transcription factor latent in the cytoplasm; the gene (<it>STAT3</it>) is activated by a wide range of cytokines, and may play a role in lung development and asthma pathogenesis.</p> <p>Methods</p> <p>We genotyped six single nucleotide polymorphisms (SNPs) in the <it>STAT3 </it>gene in a cohort of 401 Caucasian adult asthmatics. The associations between each SNP and forced expiratory volume in 1 second (FEV₁), as a percent of predicted, at the baseline exam were tested using multiple linear regression models. Longitudinal analyses involving repeated measures of FEV₁were conducted with mixed linear models. Haplotype analyses were conducted using imputed haplotypes. We completed a second association study by genotyping the same six polymorphisms in a cohort of 652 Caucasian children with asthma.</p> <p>Results</p> <p>We found that three polymorphisms were significantly associated with baseline FEV₁: homozygotes for the minor alleles of each polymorphism had lower FEV₁than homozygotes for the major alleles. Moreover, these associations persisted when we performed an analysis on repeated measures of FEV₁over 8 weeks. A haplotypic analysis based on the six polymorphisms indicated that two haplotypes were associated with baseline FEV₁. Among the childhood asthmatics, one polymorphism was associated with both baseline FEV₁and the repeated measures of FEV₁over 4 years.</p> <p>Conclusion</p> <p>Our results indicate that genetic variants in <it>STAT3</it>, independent of asthma treatment, are determinants of FEV₁in both adults and children with asthma, and suggest that <it>STAT3 </it>may participate in inflammatory pathways that have an impact on level of lung function.</p>