TY - JOUR
T1 - CD14 tobacco gene-environment interaction modifies asthma severity and immunoglobulin E levels in Latinos with asthma
AU - Choudhry, Shweta
AU - Avila, Pedro C.
AU - Nazario, Sylvette
AU - Ung, Ngim
AU - Kho, Jennifer
AU - Rodriguez-Santana, Jose R.
AU - Casal, Jesus
AU - Tsai, Hui Ju
AU - Torres, Alfonso
AU - Ziv, Elad
AU - Toscano, Monica
AU - Sylvia, Jody Senter
AU - Alioto, Maria Elena
AU - Salazar, Michael
AU - Gomez, Ivan
AU - Fagan, Joanne K.
AU - Salas, Jorge
AU - Lilly, Craig
AU - Matallana, Henry
AU - Castro, Richard A.
AU - Selman, Moises
AU - Weiss, Scott T.
AU - Ford, Jean G.
AU - Drazen, Jeffrey M.
AU - Rodriguez-Cintron, William
AU - Chapela, Rocio
AU - Silverman, Edwin K.
AU - Burchard, Esteban González
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2005/7/15
Y1 - 2005/7/15
N2 - Background: A recent family-based genomewide 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 single nucleotide polymorphisms (SNPs) in the CD14 gene by sequencing 72 Puerto Ricans, Mexicans, and African Americans with asthma. Three SNPs, -810, -159, and +1437, were further genotyped in families with asthma. Among all subjects with asthma 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. Subjects with asthma with the GG or GC genotypes who were exposed to ETS had mean baseline FEV 1 (% predicted) values 8.6% lower than subjects not exposed to ETS (p = 0.03). As previously observed in whites, 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. Conclusions: Our data suggest a gene-by-environment interaction between CD14 genotypes and ETS1 which affects pulmonary function and IgE levels among Latinos with asthma.
AB - Background: A recent family-based genomewide 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 single nucleotide polymorphisms (SNPs) in the CD14 gene by sequencing 72 Puerto Ricans, Mexicans, and African Americans with asthma. Three SNPs, -810, -159, and +1437, were further genotyped in families with asthma. Among all subjects with asthma 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. Subjects with asthma with the GG or GC genotypes who were exposed to ETS had mean baseline FEV 1 (% predicted) values 8.6% lower than subjects not exposed to ETS (p = 0.03). As previously observed in whites, 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. Conclusions: Our data suggest a gene-by-environment interaction between CD14 genotypes and ETS1 which affects pulmonary function and IgE levels among Latinos with asthma.
KW - Asthma genetics
KW - CD14
KW - Gene-environment interaction
KW - IgE
KW - Latinos
KW - Tobacco
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U2 - 10.1164/rccm.200409-1232OC
DO - 10.1164/rccm.200409-1232OC
M3 - Article
C2 - 15879416
AN - SCOPUS:22144450345
SN - 1073-449X
VL - 172
SP - 173
EP - 182
JO - American journal of respiratory and critical care medicine
JF - American journal of respiratory and critical care medicine
IS - 2
ER -