Polymorphisms in signal transducer and activator of transcription 3 and lung function in asthma
Background: 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 (STAT3) is activated by a wide range of cytokines, and m...
| Main Authors: | , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
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BioMed Central Ltd
2010
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| Online Access: | http://hdl.handle.net/1721.1/58709 |
| _version_ | 1810978969863847936 |
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| author | Litonjua, Augusto A. Tantisira, Kelan G. Lake, Stephen Lazarus, Ross Richter, Brent G. Gabriel, Stacey B. Silverman, Eric S. Weiss, Scott T. |
| author2 | Whitehead Institute for Biomedical Research |
| author_facet | Whitehead Institute for Biomedical Research Litonjua, Augusto A. Tantisira, Kelan G. Lake, Stephen Lazarus, Ross Richter, Brent G. Gabriel, Stacey B. Silverman, Eric S. Weiss, Scott T. |
| author_sort | Litonjua, Augusto A. |
| collection | MIT |
| description | Background: 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 (STAT3) is activated by a wide range of cytokines, and may play a role in lung development and asthma pathogenesis. Methods: We genotyped six single nucleotide polymorphisms (SNPs) in the STAT3 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 FEV1 were 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. Results: We found that three polymorphisms were significantly associated with baseline FEV1: homozygotes for the minor alleles of each polymorphism had lower FEV1 than homozygotes for the major alleles. Moreover, these associations persisted when we performed an analysis on repeated measures of FEV1 over 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 FEV1 and the repeated measures of FEV1 over 4 years. Conclusion: Our results indicate that genetic variants in STAT3, independent of asthma treatment, are determinants of FEV1 in both adults and children with asthma, and suggest that STAT3 may participate in inflammatory pathways that have an impact on level of lung function. |
| first_indexed | 2024-09-23T09:35:31Z |
| format | Article |
| id | mit-1721.1/58709 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T09:35:31Z |
| publishDate | 2010 |
| publisher | BioMed Central Ltd |
| record_format | dspace |
| spelling | mit-1721.1/587092022-09-26T12:30:20Z Polymorphisms in signal transducer and activator of transcription 3 and lung function in asthma Litonjua, Augusto A. Tantisira, Kelan G. Lake, Stephen Lazarus, Ross Richter, Brent G. Gabriel, Stacey B. Silverman, Eric S. Weiss, Scott T. Whitehead Institute for Biomedical Research Gabriel, Stacey B. Background: 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 (STAT3) is activated by a wide range of cytokines, and may play a role in lung development and asthma pathogenesis. Methods: We genotyped six single nucleotide polymorphisms (SNPs) in the STAT3 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 FEV1 were 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. Results: We found that three polymorphisms were significantly associated with baseline FEV1: homozygotes for the minor alleles of each polymorphism had lower FEV1 than homozygotes for the major alleles. Moreover, these associations persisted when we performed an analysis on repeated measures of FEV1 over 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 FEV1 and the repeated measures of FEV1 over 4 years. Conclusion: Our results indicate that genetic variants in STAT3, independent of asthma treatment, are determinants of FEV1 in both adults and children with asthma, and suggest that STAT3 may participate in inflammatory pathways that have an impact on level of lung function. National Heart, Lung, and Blood Institute 2010-09-24T18:32:09Z 2010-09-24T18:32:09Z 2005-06 2004-12 2010-09-03T16:23:22Z Article http://purl.org/eprint/type/JournalArticle 1465-9921 http://hdl.handle.net/1721.1/58709 Respiratory Research. 2005 Jun 03;6(1):52 15935090 en http://dx.doi.org/10.1186/1465-9921-6-52 Respiratory Research Creative Commons Attribution http://creativecommons.org/licenses/by/2.0 Litonjua et al.; licensee BioMed Central Ltd. application/pdf BioMed Central Ltd BioMed Central Ltd |
| spellingShingle | Litonjua, Augusto A. Tantisira, Kelan G. Lake, Stephen Lazarus, Ross Richter, Brent G. Gabriel, Stacey B. Silverman, Eric S. Weiss, Scott T. Polymorphisms in signal transducer and activator of transcription 3 and lung function in asthma |
| title | Polymorphisms in signal transducer and activator of transcription 3 and lung function in asthma |
| title_full | Polymorphisms in signal transducer and activator of transcription 3 and lung function in asthma |
| title_fullStr | Polymorphisms in signal transducer and activator of transcription 3 and lung function in asthma |
| title_full_unstemmed | Polymorphisms in signal transducer and activator of transcription 3 and lung function in asthma |
| title_short | Polymorphisms in signal transducer and activator of transcription 3 and lung function in asthma |
| title_sort | polymorphisms in signal transducer and activator of transcription 3 and lung function in asthma |
| url | http://hdl.handle.net/1721.1/58709 |
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