Publications

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 FEV1 (% 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 ETS, which affects pulmonary function and IgE levels among Latinos with asthma.

The last century experienced remarkable advances in the classification, diagnosis, and understanding of the pathogenesis of the interstitial lung diseases. Technological advances, particularly physiologic testing, lung imaging studies, bronchoalveolar lavage, surgical lung biopsy, and histopathologic assessment, improved our understanding of these entities. In particular, the advent of high-resolution computed tomography, the narrowed pathologic definition of usual interstitial pneumonia, and recognition of the prognostic importance of separating usual interstitial pneumonia from other idiopathic interstitial pneumonia patterns have profoundly changed the approach to these processes. Most recently, genetic medicine, the use of new technologies (e.g., microarrays, mass spectroscopic analysis of proteins, and laser capture microdissection), and the development of animal models have had a major impact on understanding the pathogenesis and potential molecular targets for interfering with fibrogenesis. This article highlights some of the advances and changes in clinical practice that took place in the management of patients with interstitial lung diseases over the last century.