The Study on Environmental and Genetic factors of Asthma

Autor: Wang Tsu-Nai, 王姿乃
Rok vydání: 2000
Druh dokumentu: 學位論文 ; thesis
Popis: 88
This study was divided into three parts to explore the associations between asthma and environmental factors and genetic components. The first part was to estimate the contribution of indoor and outdoor air pollution to the one year prevalence of adolescent asthma after taking personal susceptibility and other potential risk factors. The second part was to explore the family aggregation of asthma and inheritance component by segregation analysis. The third part was to assess the association between asthma and the polymorphisms of three candidate genes, and to determine the involvement of the TNFa, TNFb and FceRIb genes in the genetic determination of asthma. The results were followings: （1）A large-scaled cross-sectional study was conducted among 165,173 junior high school students aged 11 to 16 yrs in Kaohsiung and Pintong areas in Taiwan, from October 1995 to June 1996. Each student and his/her parents participating in the study completed a video and a written International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire about symptoms of wheezing and allergies, passive smoking, and demographic variables. After adjusting for potential confounders, adolescents exposed to cigarette smoking (odds ratio=1.29, 95% confidence interval(CI) 1.17-1.42) and environmental tobacco smoke(ETS) (odds ratio=1.08, 95% confidence interval : 1.05-1.12) were found to have a higher risk of asthma. Total suspended particulates, nitrogen dioxide, carbon monoxide, ozone and airborne dust particles all displayed an independent association with asthma, respectively, after controlling for potential confound variables. There were no selection biases in this community-based study, which provides evidence that passive smoking and long term, high average outdoor air pollution are independent risk factors of asthma. (2) Although asthma has a significant heritable component, the mode of inheritance remains controversial. Segregation analysis for asthma was performed with and without a history of atopic diseases (dermatitis and rhinitis) after adjusting for environmental factors. To investigate whether asthma may be inherited through a major gene with two alleles, the REGD program of the SAGE package was conducted in 1,990 individuals from 227 families with at least one asthmatic children. When the variables of atopic disease and environmental factors were included in the model as covariates, the models for a two-allele gene with a recessive or codominant inheritance could not be rejected, and Akaike''s Information Criterion (AIC) was smaller (1377.13) for the recessive model than all the other models tested, assuming a major gene with a population frequency of 0.56±0.04. Under the assumptions of the applied segregation, at least one major gene exists which could be a gene involved also in allergy. However, the data suggest that a single locus gene explains only a portion of asthma cases that is related to the history of atopic diseases. We suggest that a polygenic /multifactorial (genetic and environmental factors) influence with a recessive component inheritance may be involved in the pathogenesis of asthma. （3）Asthma is a chronic disease which interact by genes and environmental factors. Some candidate genes are involved in the etiology of asthma. The study aim was to assess the association between asthma and the polymorphisms of TNFa-308, LTaNcoI and FceRIb-gly237glu. There are no differences between the asthma and non-asthma of polymorphisms of TNFa-308, LTaNcoI. The FceRIb-gly237glu mutant rate of asthma children was significantly higher than that of non-asthma children. Asthma children（
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