CD14 tobacco gene-environment interaction modifies asthma severity and immunoglobulin E levels in Latinos with asthma

Shweta Choudhry, Pedro C. Avila, Sylvette Nazario, Ngim Ung, Jennifer Kho, Jose R. Rodriguez-Santana, Jesus Casal, Hui Ju Tsai, Alfonso Torres, Elad Ziv, Monica Toscano, Jody Senter Sylvia, Maria Elena Alioto, Michael Salazar, Ivan Gomez, Joanne K. Fagan, Jorge Salas, Craig Lilly, Henry Matallana, Richard A. CastroMoises Selman, Scott T. Weiss, Jean G. Ford, Jeffrey M. Drazen, William Rodriguez-Cintron, Rocio Chapela, Edwin K. Silverman, Esteban González Burchard

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)173-182
Number of pages10
JournalAmerican journal of respiratory and critical care medicine
Volume172
Issue number2
DOIs
StatePublished - Jul 15 2005

Keywords

  • Asthma genetics
  • CD14
  • Gene-environment interaction
  • IgE
  • Latinos
  • Tobacco

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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