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Published ahead of print on May 5, 2005, doi:10.1164/rccm.200409-1232OC

Am. J. Respir. Crit. Care Med., Volume 172, Number 2, July 2005, 173-182

A more recent version of this article appeared on July 15, 2005
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Submitted on September 17, 2004
Accepted on April 21, 2005

CD14-Tobacco Gene-Environment Interaction Modify Asthma Severity and IgE Levels in Latino Asthmatics

Shweta Choudhry1, Pedro C Avila2, Sylvette Nazario3, Ngim Ung1, Jennifer Kho1, Jose R Rodriguez-Santana4, Jesus Casal3, Hui-Ju Tsai1, Alfonso Torres3, Elad Ziv2, Monica Toscano1, Jody Senter Sylvia5, MariaElena Alioto2, Michael Salazar1, Ivan Gomez3, Joanne K Fagan6, Jorge Salas7, Craig Lilly5, Henry Matallana1, and Esteban Gonzalez Burchard1*

1 University of California, San Francisco, San Francisco, CA, USA; Lung Biology Center, San Francisco General Hospital, San Francisco, CA, USA, 2 University of California, San Francisco, San Francisco, CA, USA, 3 San Juan VAMC, University of Puerto Rico School of Medicine, San Juan, PR, Puerto Rico, 4 Pediatric Pulmonary Program of San Juan, San Juan, PR, Puerto Rico, 5 Brigham and Women's Hospital, Boston, MA, USA, 6 The Harlem Lung Center, Harlem Hospital and Columbia University, New York, NY, USA, 7 Instituto Nacional de Enfermedades Respiratorias (INER), Mexico City, Distrito Federal, Mexico

* To whom correspondence should be addressed. E-mail: esteban.burchard{at}ucsf.edu.

Background: A recent family-based genome-wide screen revealed linkage between the 5q31 region and the diagnosis of asthma, but only in those exposed to environmental tobacco smoke (ETS). Among the candidate genes in this region is CD14. Methods: To determine whether polymorphisms in the CD14 gene are related to this gene-by-environment interaction in Latinos, we used both family-based and cross-sectional cohort analysis to test for interactions between CD14 genotypes/haplotypes, exposure to ETS and asthma-related phenotypes in 659 Mexican and Puerto Rican families. Results: We identified 21 SNPs in CD14 gene by sequencing 72 Puerto Rican, Mexican and African American asthmatics. Three SNPs -810, -159 and +1437 were further genotyped in asthmatic families. Among all asthmatic subjects exposed to ETS, without regard to ethnicity, CD14 +1437 genotypes were associated with asthma severity. SNP+1437 GG or GC genotypes were significantly associated with lower baseline FEV1 using both family-based (p=0.0009) and cross-sectional cohort (p=0.03) analyses. Asthmatic subjects with the GG or GC genotypes who were exposed to ETS had mean baseline FEV1 (% predicted) values 8.6% lower than subjects not exposed to ETS (p =0.03). As previously observed in Caucasians, we found an interaction between plasma IgE levels, SNP -159 genotypes, and ETS exposure (p = 0.0002). The lowest IgE levels were in those subjects with the TT genotype and who were exposed to ETS regardless of ethnicity.
Key words: Gene-Environment Interaction, CD14, Tobacco, Asthma Genetics, IgE




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