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TNF Polymorphisms Modify Endotoxin Exposure Associated Longitudinal Lung Function Decline
  1. Hongxi Zhang
  1. Shanghai Putuo District People’s Hospital, China
    1. Jingqing Hang
    1. Shanghai Putuo District People’s Hospital, China
      1. Xiaorong Wang
      1. Harvard School of Public Health, United States
        1. Wei Zhou
        1. Harvard School of Public Health, United States
          1. Bixiong Sun
          1. Shanghai Putuo District People’s Hospital, China
            1. Helian Dai
            1. Shanghai Putuo District People’s Hospital, China
              1. Li Su
              1. Harvard School of Public Health, United States
                1. David C Christiani (dchris{at}hohp.harvard.edu)
                1. Harvard School of Public Health, United States

                  Abstract

                  Objectives: Endotoxin exposure induces airway inflammation, hyperresponsiveness, and higher expression of tumor necrosis factor (TNF). This study was conducted to investigate whether TNF polymorphisms modify the effect of endotoxin exposure on chronic declines in lung function. Methods: Association between TNF and LTA polymorphisms, endotoxin exposure and lung function was analyzed in 263 cotton workers and 230 silk workers as a reference group, who were prospectively followed for 20-years. Multiple linear regression models were used to assess the association, with adjustment for smoking and other covariates. Results: Endotoxin exposure was associated with faster lung function decline among genotypes associated with higher TNF expression levels, with the estimates of annual FEV1 change in relation to endotoxin exposure by –2.9 ml and -6.8 ml in the G/G and G/A+AA genotypes, respectively, for the TNF polymorphism; and –2.0 ml, –4.0 ml, and -3.6 ml in A/A, A/G, and G/G genotypes, respectively, for the LTA polymorphism. When joint effects of endotoxin exposure and smoking were considered, the effect modification of TNF and LTA polymorphisms was prominent in never smokers. Conclusions: TNF and LTA polymorphisms may modify the association between occupational endotoxin exposure and longitudinal lung function decline, which was more clearly observed in never smokers among these subjects.

                  • TNF polymorphisms
                  • longitudinal changes in lung function
                  • occupational exposure to endotoxin

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