CD14 tobacco gene-environment interaction modifies asthma severity and immunoglobulin E levels in 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.
Choudhry
Shweta
S
University of California-San Francisco, DNA Bank/Lung Biology Center, San Francisco General Hospital, Bldg. 30, 5th Floor, Room 3501H, 1001 Potrero Avenue, San Francisco, CA 94110, USA.
Avila
Pedro C
PC
Nazario
Sylvette
S
Ung
Ngim
N
Kho
Jennifer
J
Rodriguez-Santana
Jose R
JR
Casal
Jesus
J
Tsai
Hui-Ju
HJ
Torres
Alfonso
A
Ziv
Elad
E
Toscano
Monica
M
Sylvia
Jody Senter
JS
Alioto
Mariaelena
M
Salazar
Michael
M
Gomez
Ivan
I
Fagan
Joanne K
JK
Salas
Jorge
J
Lilly
Craig
C
Matallana
Henry
H
Castro
Richard A
RA
Selman
Moises
M
Weiss
Scott T
ST
Ford
Jean G
JG
Drazen
Jeffrey M
JM
Rodriguez-Cintron
William
W
Chapela
Rocio
R
Silverman
Edwin K
EK
Burchard
Esteban González
EG
D000293:Adolescent; D001249:Asthma / Q000188:drug therapy / Q000208:ethnology / Q000235:genetics / Q000503:physiopathology*; D001993:Bronchodilator Agents / Q000627:therapeutic use; D002648:Child; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006630:Hispanic or Latino; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood*; D015810:Linkage Disequilibrium; D018950:Lipopolysaccharide Receptors / Q000235:genetics*; D008168:Lung / Q000503:physiopathology; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012720:Severity of Illness Index; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
D001993:Bronchodilator Agents; D018950:Lipopolysaccharide Receptors; D014028:Tobacco Smoke Pollution; D007073:Immunoglobulin E