Effects of Polymorphic Variations in Tumor Necrosis Factor Alpha and Occupational Exposure to Grain Dust on Longitudinal Decline in Pulmonary Function

ABSTRACT

Background:Longitudinal declines in pulmonary function are associated with individuals experiencing occupational exposure to organic dusts in combination with lifestyle factors such as cigarette smoking and with genetic factors, and interactions between these factors. Objective:To investigate the relationship between polymorphism of genes encoding Tumor Necrosis Factor Alpha (TNF-α) and longitudinal lung function decline in grain workers exposed to grain dust. Method:Male grain handlers who participated in the Saskatchewan Grain Workers Surveillance Program from 2002 through 2005 provided demographic, occupational, lifestyle, and respiratory symptoms information as well as pulmonary function measurements and DNA for genotyping. Marginal models using the generalized estimating equations approach were fitted by using a SAS PROC GENMOD to predict the annual decline in Forced Expired Volume in one second (FEV₁) and Forced Vital Capacity (FVC). Results:Smoking intensity contributed to the decline in FEV_1.Among ∗1/∗1 homozygotes and ∗1/∗2 heterozygotes, grain workers with <10 years in the grain industry had significantly lower FEV₁declines compared to those of the other two exposure groups (>10 and ≤20 years, and >20 years in the grain industry). The annual declines in FEV₁for grain workers who were either ∗1/∗1 homozygote or ∗1/∗2 heterozygote and had been in the grain industry for <10 years were lower by comparison to those of grain workers who were ∗2/∗2 genotype and had been in the industry for <10 years. Conclusion:This research demonstrates that years in the grain industry is an effect modifier between TNF-α 308 genotype and longitudinal decline in FEV₁in male subjects exposed to grain dust.

KEYWORDS:

• Grain dust
• longitudinal decline
• pulmonary function
• TNF-α