Exposure to environmental tobacco smoke, human E-cadherin C-160A polymorphism, and childhood asthma.
BACKGROUND
Environmental tobacco smoke (ETS) is a risk factor for asthma. Importantly, cigarette smoke can decrease the adherence of epithelial cells and increase detachment. The adhesion molecule E-cadherin (CDH1) has an essential role in the formation of epithelial junction. Turnover of the extracellular matrix, which is characterized by airway remodeling, depends on the imbalance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinase (TIMPs).


OBJECTIVE
To evaluate the effects of ETS exposure and CDH1, MMP-3, and TIMP-1 genetic polymorphisms on childhood asthma.


METHODS
The CDH1 C-160A, MMP-3 -1171, and TIMP-1 T372C genotypes were identified by polymerase chain reaction in 299 asthmatic children and 383 healthy controls.


RESULTS
More ETS exposure (>5 vs 0 cigarettes/day; odds ratio [OR], 1.45; 95% confidence interval [CI], 1.05-2.01) and the presence of CDH1 AA/CA genotypes (OR, 1.53; 95% CI, 1.08-2.17) were associated with childhood asthma. Compared with children with less ETS exposure (0-5 cigarettes/day) and the CDH1 CC genotype, those with less ETS exposure and the CDH1 AA/CA genotypes and those with more ETS exposure and the CDH1 CC genotype had a moderate risk of asthma. The greatest risk for asthma was in children with more ETS exposure and the CDH1 AA/CA genotypes (OR, 3.03; 95% CI, 1.81-5.06), and this interaction between CDH1 polymorphism and ETS exposure was significant. In addition, asthma cases with more ETS exposure or the CDH1 AA/CA genotypes had obviously increased eosinophil counts.


CONCLUSIONS
Susceptible CDH1 genotypes might modulate the development of asthma, especially for children exposed to ETS.
Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics, Tungs' Taichung Metroharbor Hospital, Taichung, Taiwan; Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; Department of Rehabilitation, Jen-Teh Junior College of Medicine, Nursing, and Management, Miaoli County, Taiwan.
Ming-Fuu
MF
Wang
Sheng-Hung
SH
Kuo
Chun-Huang
CH
Huang
Yi-Ju
YJ
Chen
Shin-Hua
SH
Lin
Chiung-Ju
CJ
Lee
Ko-Huang
KH
Lue
Shao-Chun
SC
Wu
Chung-Yen
CY
Cho
Ruey-Hong
RH
Wong
D015703:Antigens, CD; D001249:Asthma / Q000453:epidemiology / Q000235:genetics*; D015820:Cadherins / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D004781:Environmental Exposure / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000235:genetics; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D013624:Taiwan / Q000453:epidemiology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D014028:Tobacco Smoke Pollution; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3