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诱导型一氧化氮合酶与哮喘严重性、血清总IgE及外周血嗜酸性粒细胞水平间的相关性研究

2007/03/09

    2007年1月，发表于Thorax上的一篇文章研究了 230个哮喘家族（包括842名哮喘患者）中诱导型一氧化氮合成酶（iNOS）基因重复多态性与哮喘表型的相关性。他们鉴定了iNOS基因四个重复序列多态性（包括启动子区的CCTTT、内含子2 的GT、内含子4的GT及内含子5的CA序列），其中内含子4的GT重复与外周血嗜酸性粒细胞水平及哮喘严重性密切相关；启动子区的CCTTT重复与血清IgE水平相关。他们的研究首次发现，内含子4的等位基因3（GT重复15次）与哮喘严重性及嗜酸性粒细胞水平密切相关；该等位基因与血清NO水平也相关联。他们还发现iNOS基因启动子重复多态性与血清IgE水平有关，启动子区为等位基因4（CCTTT重复12次）的哮喘患者，血清IgE与NO均呈现高水平表达。他们的研究结果表明，iNOS基因重复多态性与哮喘严重性、嗜酸性粒细胞水平及血清IgE水平密切相关。进而，为阐明NO在哮喘发病机制中的作用，提供了有力证据。
 
（毛辉 成都，四川大学华西医院呼吸科  610041 摘译）
(Thorax， 2007， 62: 16-22)

 

Association of inducible nitric oxide synthase with asthma severity, total serum immunoglobulin E and blood eosinophil levels

Jyotsna Batra, Tej Pratap Singh, Ulanganathan Mabalirajan, Aditi Sinha, Rajendra Prasad, and Balaram Ghosh Thorax 2007; 62: 16-22.

Background: Nitric oxide is released by immune, epithelial and endothelial cells, and plays an important part in the pathophysiology of asthma. 

Objective: To investigate the association of inducible nitric oxide synthases (iNOS) gene repeat polymorphisms with asthma. 

Methods: 230 families with asthma (842 individuals) were recruited to identify and establish the genetic association of iNOS repeats with asthma and associated phenotypes. Serum nitric oxide levels in selected individuals were measured and correlated with specific genotypes. Multiple logistic regression analysis was performed to determine the effect of age and sex. 

Results: A total of four repeats—a (CCTTT)n promoter repeat, a novel intron 2 (GT)n repeat (BV680047 [GenBank] ), an intron 4 (GT)n repeat (AFM311ZB1) and an intron 5 (CA)n repeat (D17S1878)—were identified and genotyped. A significant transmission distortion to the probands with asthma was seen for allele 3 of the AFM311ZB1 gene (p = 0.006). This allele was also found to be significantly associated with percentage blood eosinophils (p<0.001) and asthma severity (p = 0.04). Moreover, it was functionally correlated with high serum nitric oxide levels (p = 0.006). Similarly, the promoter repeat was found to be associated with serum total immunoglobulin (Ig)E (p = 0.028). Individuals carrying allele 4 of this repeat have high serum IgE (p<0.001) and nitric oxide levels (p = 0.03). 

Conclusion: This is the first study to identify the repeat polymorphisms in the iNOS gene that are associated with severity of asthma and eosinophils. The functional relevance of the associated alleles with serum nitric oxide levels was also shown. Therefore, these results could be valuable in elucidating the role of nitric oxide in asthma pathogenesis. 
 


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