Tobacco GeneûEnvironment Interactions & Minority Asthmatics

Institution:	University of California, San Francisco
Investigator(s):	Shweta Choudhry, Ph.D., MSc.
Award Cycle:	2006 (Cycle 15)	Grant #: 15KT-0008H	Award: $299,500
Subject Area:	Pulmonary Disease
Award Type:	New Investigator Awards

Abstracts

Initial Award Abstract

Asthma is a common disease that results from both genetic and environmental risk factors. Environmental tobacco smoke (ETS) has been associated with asthma and asthma severity. Although virtually all individuals are exposed to ETS, only a subset goes on to develop asthma or have an increase in asthma symptoms. This would suggest that the response to ETS varies among individuals, which may be explained by genetic susceptibility. We have previously demonstrated that there are gene-environment interactions between genetic variant in the CD14 gene and ETS exposure that result in more severe asthma among Mexican and Puerto Rican children. Additionally gene-environment interactions that are likely to be important to asthma include interactions between ETS exposure and genes related to xenobiotic metabolism and oxidative stress pathways. Despite the fact that asthma prevalence and mortality are especially high in minority populations, they, for the most part have not been included in asthma clinical, genetic and/or epidemiologic research. Therefore, we will focus our studies of these interactions on three ethnic minority populations: African Americans, Puerto Ricans and Mexicans. We have carefully selected fifteen candidate genes from pathways involved in xenobiotic metabolism and oxidative stress. These genes were selected based on our preliminary studies of asthma-related clinical characteristics in minority populations and from published literature on genetic association studies performed in other non-minority populations. The Specific Aims of this proposal include performing a high throughput screen of these asthma candidate genes in 700 Mexican and Puerto Rican families and 467 African American asthma cases and controls. We will analyze these genes for gene-environment interactions with ETS exposure and their association with asthma and asthma severity. We will then replicate positive associations from high throughput screen in additional but separate populations of Latinos (GALA 2, n=1600) and African American asthma cases and controls (SAGE 2, n=600). The focus on gene-ETS interactions in minority populations will help to better understand the striking population-based differences observed with respect to asthma prevalence and severity. Our findings may contribute to better understanding of the etiology of asthma as it relates to all populations. Furthermore, our results may provide a way to identify individuals at high risk of more severe asthma due to ETS exposure. This information will be of great benefit in designing intervening strategies that aim to reduce the toll taken by severe asthma in minority populations. By gaining a better understanding of the interaction between genetic factors and ETS, this proposal is consistent with the goal established by TRDRP to better understand the impact of tobacco smoke on development and progression of a disease to the betterment of health for all populations.

Publications

Genome-wide screen for asthma in Puerto Ricans: evidence for assocation with 5q23 region
Periodical: Human Genetics			Index Medicus:
Authors: Choudhry, S., Taub, M., Mei, R., Rodriquez-Santana, J., Rodriguez-Cintron, W., Shriver, M.				ART
Yr: 2008	Vol: 123	Nbr:	Abs:	Pg: 455-68

ORMDL3 gene is associated with asthma in three ethnically diverse populations
Periodical: American Journal of Respiratory and Critical Care Medicine			Index Medicus:
Authors: Galanter, J. Choudhry, S., Eng, C., Nazario, S., Rodriquez-Santana, J.R., Casal, J., Torre				ART
Yr: 2208	Vol: 177	Nbr:	Abs:	Pg: 1194-2000

Ethinic-specific differences in broncholdilator responsiveness among African-American, Puerto Ricans, Mexican-Americans with asthma
Periodical: Journal of Asthma			Index Medicus:
Authors: Naqvi, M., Thyne, S., Choundry, S., Tsai, H.J., Navarro, D., Castro, R.A., Nazario, S., Ro				ART
Yr: 2007	Vol: 44	Nbr:	Abs:	Pg: 639-48

Asssociation between IgE levels and asthma severity among African-American, Mexican, and Puerto Ricans, patients with asthma
Periodical: Journal of Allergy and Clinical Immunology			Index Medicus:
Authors: Naqvi, M., Choundry, S., Tsai, H.J., Thyne, S., Navarro, D., Rodriquez-Santana, J.R., Casa				ART
Yr: 2007	Vol: 120	Nbr:	Abs:	Pg: 137-43

Genetic ancestry and risk of breast cancer among US Latinas.
Periodical: Cancer Research			Index Medicus:
Authors: Fejerman L, John E, Huatsman S, Beckman K, Choudhry S, Perez-Stable E, Burchard E, Ziv E				ART
Yr: 2008	Vol: 68	Nbr: 23	Abs:	Pg: 9723-9728

Differences in allergic sensitization by self-reported race and genetic ancestry.
Periodical: Journal of Allergy and Clinical Immunology			Index Medicus:
Authors: Yang, Burchard, Choudhry, Johnson, Ownby, Favro, Chen, Akana, Ha, Kwok, Krajenta, Havstad,				ART
Yr: 2008	Vol: 122	Nbr: 4	Abs:	Pg: 820-827

Comparing genetic ancestry and self-described race in African American born in the United States and in Africa
Periodical: Cancer Epidemiology Biomarkers and Prevention			Index Medicus:
Authors: Yeager R, Avila-Bront A, Abdul K, Nolan P, Grann V, Birchette M, Choudhry S, Burchard E, B				ART
Yr: 2008	Vol:	Nbr: 17	Abs:	Pg: 1329-1338

Genetic ancestry in lung-function predictions.
Periodical: New England Journal of Medicine			Index Medicus:
Authors: Kumar R, Seibold MA, Aldrich MC, Williams LK, Reiner AP, Colangelo L, Galanter J, Gignoux				ART
Yr: 2010	Vol: 363	Nbr: 4	Abs:	Pg: 321-30

GSNO reductase and beta2-adrenergic receptor gene-gene interaction: bronchodilator responsiveness to albuterol.
Periodical: Pharmacogenetics and Genomics			Index Medicus:
Authors: Choudhry S, Que LG, Yang Z, Liu L, Eng C, Kim SO, Kumar G, Thyne S, Chapela R, Rodriquez-S				ART
Yr: 2010	Vol: 20	Nbr: 6	Abs:	Pg: 351-8

The role of LTA4H and ALOX5AP genes in the risk for asthma in Latinos.
Periodical: Clinical and Experimental Allergy			Index Medicus:
Authors: Via M, De Giacomo A, Corvol H, Eng C, Seibold MA, Gillett C, Galanter J, Sen S, Tcheurekdj				ART
Yr: 2010	Vol: 40	Nbr: 4	Abs:	Pg: 582-9

Ancestry-related assortative mating in Latino populations.
Periodical: Genome Biology			Index Medicus:
Authors: Risch N, Choudhry S, Via M, Basu A, Sebro R, Eng C, Beckman K, Thyne S, Capela R, Rodrigue				ART
Yr: 2009	Vol: 10	Nbr: 11	Abs:	Pg: R132

Genetic ancestry modifies pharmacogenetic gene-gene interaction for asthma.
Periodical: Pharmacogenetics and Genomics			Index Medicus:
Authors: Corvol H, De Giacomo A, Eng C, Seibold M, Ziv E, Chapela R, Rodriguez-Santana JR, Rodrigue				ART
Yr: 2009	Vol: 19	Nbr: 7	Abs:	Pg: 489-96

Genome-wide screen for asthma in Puerto Ricans: evidence for assocation with 5q23 region
Periodical: Human Genetics			Index Medicus:
Authors: Choudhry, S., Taub, M., Mei, R., Rodriquez-Santana, J., Rodriguez-Cintron, W., Shriver, M.				ART
Yr: 2008	Vol: 123	Nbr:	Abs:	Pg: 455-68

ORMDL3 gene is associated with asthma in three ethnically diverse populations
Periodical: American Journal of Respiratory and Critical Care Medicine			Index Medicus:
Authors: Galanter, J. Choudhry, S., Eng, C., Nazario, S., Rodriquez-Santana, J.R., Casal, J., Torre				ART
Yr: 2208	Vol: 177	Nbr:	Abs:	Pg: 1194-2000

Ethinic-specific differences in broncholdilator responsiveness among African-American, Puerto Ricans, Mexican-Americans with asthma
Periodical: Journal of Asthma			Index Medicus:
Authors: Naqvi, M., Thyne, S., Choundry, S., Tsai, H.J., Navarro, D., Castro, R.A., Nazario, S., Ro				ART
Yr: 2007	Vol: 44	Nbr:	Abs:	Pg: 639-48

Asssociation between IgE levels and asthma severity among African-American, Mexican, and Puerto Ricans, patients with asthma
Periodical: Journal of Allergy and Clinical Immunology			Index Medicus:
Authors: Naqvi, M., Choundry, S., Tsai, H.J., Thyne, S., Navarro, D., Rodriquez-Santana, J.R., Casa				ART
Yr: 2007	Vol: 120	Nbr:	Abs:	Pg: 137-43

Genetic ancestry and risk of breast cancer among US Latinas.
Periodical: Cancer Research			Index Medicus:
Authors: Fejerman L, John E, Huatsman S, Beckman K, Choudhry S, Perez-Stable E, Burchard E, Ziv E				ART
Yr: 2008	Vol: 68	Nbr: 23	Abs:	Pg: 9723-9728

Differences in allergic sensitization by self-reported race and genetic ancestry.
Periodical: Journal of Allergy and Clinical Immunology			Index Medicus:
Authors: Yang, Burchard, Choudhry, Johnson, Ownby, Favro, Chen, Akana, Ha, Kwok, Krajenta, Havstad,				ART
Yr: 2008	Vol: 122	Nbr: 4	Abs:	Pg: 820-827

Comparing genetic ancestry and self-described race in African American born in the United States and in Africa
Periodical: Cancer Epidemiology Biomarkers and Prevention			Index Medicus:
Authors: Yeager R, Avila-Bront A, Abdul K, Nolan P, Grann V, Birchette M, Choudhry S, Burchard E, B				ART
Yr: 2008	Vol:	Nbr: 17	Abs:	Pg: 1329-1338

Genetic ancestry in lung-function predictions.
Periodical: New England Journal of Medicine			Index Medicus:
Authors: Kumar R, Seibold MA, Aldrich MC, Williams LK, Reiner AP, Colangelo L, Galanter J, Gignoux				ART
Yr: 2010	Vol: 363	Nbr: 4	Abs:	Pg: 321-30

GSNO reductase and beta2-adrenergic receptor gene-gene interaction: bronchodilator responsiveness to albuterol.
Periodical: Pharmacogenetics and Genomics			Index Medicus:
Authors: Choudhry S, Que LG, Yang Z, Liu L, Eng C, Kim SO, Kumar G, Thyne S, Chapela R, Rodriquez-S				ART
Yr: 2010	Vol: 20	Nbr: 6	Abs:	Pg: 351-8

The role of LTA4H and ALOX5AP genes in the risk for asthma in Latinos.
Periodical: Clinical and Experimental Allergy			Index Medicus:
Authors: Via M, De Giacomo A, Corvol H, Eng C, Seibold MA, Gillett C, Galanter J, Sen S, Tcheurekdj				ART
Yr: 2010	Vol: 40	Nbr: 4	Abs:	Pg: 582-9

Ancestry-related assortative mating in Latino populations.
Periodical: Genome Biology			Index Medicus:
Authors: Risch N, Choudhry S, Via M, Basu A, Sebro R, Eng C, Beckman K, Thyne S, Capela R, Rodrigue				ART
Yr: 2009	Vol: 10	Nbr: 11	Abs:	Pg: R132

Genetic ancestry modifies pharmacogenetic gene-gene interaction for asthma.
Periodical: Pharmacogenetics and Genomics			Index Medicus:
Authors: Corvol H, De Giacomo A, Eng C, Seibold M, Ziv E, Chapela R, Rodriguez-Santana JR, Rodrigue				ART
Yr: 2009	Vol: 19	Nbr: 7	Abs:	Pg: 489-96