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GENETIC VARIATION IN INDUCIBLE NITRIC OXIDE SYNTHASE PROMOTER, RESIDENTIAL TRAFFIC RELATED AIR POLLUTION AND EXHALED NITRIC OXIDE IN CHILDREN
by
Pi-chu Kaylene Lin
A Thesis Presented to the
FACULTY OF THE USC GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
MASTER OF SCIENCE
(Applied Biostatistics and Epidemiology)
AUGUST 2013
Copyright 2013 Pi-Chu Kaylene Lin
Object Description
| Title | Genetic variation in inducible nitric oxide synthase promoter, residential traffic related air pollution and exhaled nitric oxide in children |
| Author | Lin, Pi-Chu Kaylene |
| Author email | pichulin@usc.edu;kaylenelin@hotmail.com |
| Degree | Master of Science |
| Document type | Thesis |
| Degree program | Applied Biostatistics and Epidemiology |
| School | Keck School of Medicine |
| Date defended/completed | 2013-06-24 |
| Date submitted | 2013-07-29 |
| Date approved | 2013-07-29 |
| Restricted until | 2013-07-29 |
| Date published | 2013-07-29 |
| Advisor (committee chair) | Gilliland, Frank D. |
| Advisor (committee member) |
Salam, Md. Towhid Gauderman, William James |
| Abstract | Background: Fractional concentration of nitric oxide in exhaled air (FeNO) is a biomarker of airway inflammation. Nitric oxide synthase 2 (NOS2) in airway epithelium has been recognized as the major source of NO in exhaled breath. Earlier work has shown that common promoter haplotypes in NOS2 and total length of local roads around homes, a metric of residential traffic related pollution, affect FeNO level in children. ❧ Aims: The aims of this study were to examine the joint associations of NOS2 promoter haplotypes and length of local roads around homes and FeNO and to assess the influence of asthma on these associations in children. ❧ Methods: The study included 2,457 (7 to 11 year-old) children of the Southern California Children’s Health Study. FeNO was measured at school during 2005-2006. Lengths of local roads within circular buffers (50m, 100m and 200m) around the participant residence were estimated using GIS methods. Two common promoter haplotypes in NOS2 that have been associated with FeNO, asthma and lung function growth in children were selected. Linear regression was utilized to examine the independent and joint associations of NOS2 promoter haplotypes and road length measures on FeNO. ❧ Results: We observed joint effects of length of local roads within 100m and 200m buffer and the most common haplotype for FeNO (P-values for interaction ≤0.03). In children who had ≤250m of road within 100m buffer around home, those with two copies of the haplotype had significantly lower FeNO (adjusted mean FeNO=10.71ppb; 95% confidence intervals (CI): 9.10-12.61) than those with no copies (adjusted mean FeNO 14.18ppb; 95% CI: 13.09-15.36). This protective effect of the haplotype was not observed in children who had >250m road lengths within 100m buffer. Similar joint effects of this haplotype and road lengths within 200m buffer on FeNO was observed. These joint effects were not influenced by asthma. ❧ Conclusion: Our results indicate that the protective effect of a common NOS2 promoter haplotype on NO synthesis in the airway is not evident in children who live near higher levels of local traffic. |
| Keyword | CHS; Children’s Health Study; FeNO; fractional concentration of exhaled nitric oxide; htSNP; haplotype-tagging single nucleotide polymorphism; iNOS; inducible nitric oxide synthase; NO; nitric oxide; NO2; nitrogen dioxide; NOS2; nitric oxide synthase isoform 2; ROS; reactive oxygen species; SNP; single nucleotide polymorphism; TRP; traffic related pollution |
| Language | English |
| Format (imt) | application/pdf |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Provenance | Electronically uploaded by the author |
| Type | texts |
| Legacy record ID | usctheses-m |
| Contributing entity | University of Southern California |
| Rights | Lin, Pi-Chu Kaylene |
| Physical access | The author retains rights to his/her dissertation, thesis or other graduate work according to U.S. copyright law. Electronic access is being provided by the USC Libraries in agreement with the author, as the original true and official version of the work, but does not grant the reader permission to use the work if the desired use is covered by copyright. It is the author, as rights holder, who must provide use permission if such use is covered by copyright. The original signature page accompanying the original submission of the work to the USC Libraries is retained by the USC Libraries and a copy of it may be obtained by authorized requesters contacting the repository e-mail address given. |
| Repository name | University of Southern California Digital Library |
| Repository address | USC Digital Library, University of Southern California, University Park Campus MC 7002, 106 University Village, Los Angeles, California 90089-7002, USA |
| Repository email | cisadmin@dots.usc.edu |
| Filename | etd-LinPiChuKa-1868.pdf |
| Archival file | uscthesesreloadpub_Volume7/etd-LinPiChuKa-1868-0.pdf |
Description
| Title | Page 1 |
| Contributing entity | University of Southern California |
| Repository email | cisadmin@dots.usc.edu |
| Full text | GENETIC VARIATION IN INDUCIBLE NITRIC OXIDE SYNTHASE PROMOTER, RESIDENTIAL TRAFFIC RELATED AIR POLLUTION AND EXHALED NITRIC OXIDE IN CHILDREN by Pi-chu Kaylene Lin A Thesis Presented to the FACULTY OF THE USC GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree MASTER OF SCIENCE (Applied Biostatistics and Epidemiology) AUGUST 2013 Copyright 2013 Pi-Chu Kaylene Lin |
