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.
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.
Authors: Shweta Choudhry; Esteban González Burchard; Luisa N Borrell; Hua Tang; Ivan Gomez; Mariam Naqvi; Sylvette Nazario; Alphonso Torres; Jesus Casal; Juan Carlos Martinez-Cruzado; Elad Ziv; Pedro C Avila; William Rodriguez-Cintron; Neil J Risch Journal: Am J Respir Crit Care Med Date: 2006-09-14 Impact factor: 21.405
Authors: Natalie C Battle; Shweta Choudhry; Hui-Ju Tsai; Celeste Eng; Gunjan Kumar; Kenneth B Beckman; Mariam Naqvi; Kelley Meade; H George Watson; Michael Lenoir; Esteban González Burchard Journal: Am J Respir Crit Care Med Date: 2007-02-15 Impact factor: 21.405
Authors: Christine L M Joseph; L Keoki Williams; Dennis R Ownby; Jacquelyn Saltzgaber; Christine C Johnson Journal: J Allergy Clin Immunol Date: 2006-02 Impact factor: 10.793
Authors: Shweta Choudhry; Max A Seibold; Luisa N Borrell; Hua Tang; Denise Serebrisky; Rocio Chapela; José R Rodriguez-Santana; Pedro C Avila; Elad Ziv; William Rodriguez-Cintron; Neil J Risch; Esteban González Burchard Journal: Proc Am Thorac Soc Date: 2007-07
Authors: Carla J Berg; Christine M Daley; Niaman Nazir; Angel Cully; Christina M Pacheco; Taneisha Buchanan; Jasjit S Ahuwalia; K Allen Greiner; Won S Choi Journal: J Health Dispar Res Pract Date: 2012-01-01