ACE, CD14, IL4基因多型性與台灣過敏疾病關聯性之研究

Abstract

Atopic disease including allergic rhinitis and asthma, are common in the world and Taiwan. The disease are genally considered to be caused by interaction of genetic and environmental factors. In recent years, studies about genetic factor, including positional cloning, candidate gene studies and polymorphisn of candidate genes are published. But most of the study are reported by other countries. So the aim of our study was to investigate the relationship of candidate genes polymorphism and atopic disease in Taiwan. Angiotensin-converting enzyme (ACE) play a key role in the metabolism of angiotensin II and inactivation of bradykinins and tachykinins, which are potent bronchoconstrictors and mediators of airway inflammation seperatively. An insertion-deletion (I/D) polymorphism on intron 16 of ACE gene has been reported to be associated with atopic disease from other countries. CD14, a receptor of lipopolysaccharides, play a role in the polarization of naive T cell to Th1 or Th2. C -159T single nucleotide polymorphism on CD14 gene promoter region has been reported to be associated with atopic disease from other countries. IL-4 is related to IgE production and other allergic reaction. IL-4 gene intron-2 70bp repeats polymorphism has been shown to be associated with serum IL-4 level, but it’s relationship to atopic disease are not reported now. Our study will investigate the relationship of the three genetic polymorphism and atopic disease in Taiwan. We randomly select 108 children, 54 with allergic rhinitis symptom, 54 with allergic rhinitis combined asthma, as atopic children group; 38 atopic disease families including 47 adults and 49 children, as atopic disease group. Then select 96 healthy children as control group. ACE and IL-4 genotype were determined by PCR. CD14 genotype was determined by PCR and restriction analysis by Ava II. Lung function in atopic disease children was assessed by spirometry. Pharmacia cap system were performed to measure serum total IgE levels and and six commom allergen specific IgE levels. Serum eosinophil count also checked. Then we investigate the frequencies of the genotypes and alleles between study group and control group, and in different conditions. The relationship of genotype and IgE, eosinophil, lung function data also evaluated. In ACE gene polymorphism, the frequency of DD genotype was hgher in “allergic rhinitis combined asthma” children than control children ( p = 0.008). But there was no difference in the frequency of DD genotype between “only allergic rhinitis children” and control children ( p = 0.374). We also found that in Taiwaness asthma children, the rate of D allele are lower (35%) than that in Chinese asthma children (51%). Total IgE level, eosinophil count, lung function did not differe between ACE genotypes. In CD14 and IL-4 gene polymorphism, the genotype distribution was not different between atopic children group and control group. Total IgE level, eosinophil count, lung function still did not differe between genotypes. In atopic disease family, the genotype distribution of the three genetic polymorphism was not different between “with atopic symptom members” and “without atopic symptom members”. In conclusion, the result suggested that DD allele of ACE genotype was significantly associated with “allergic rhinitis combined asthma children”, but not “allergic rhinitis only children”. ACE I/D polymorphism is not related to lung function, serum total IgE level and eosinophil count. Both CD14 C/T polymorphism and IL-4 intron 2 70bp repeats polymorphism are not relate to atopic disease in Taiwaness.