Influence of genetic polymorphisms on the association between phthalate exposure and pulmonary function in the elderly.

BACKGROUND: Phthalates are prevalent environmental exposure chemicals with rising concern on various health effects, including pulmonary function. Meanwhile, elderly people are more susceptible to environmental exposure, and their decreasing lung function is an important health issue. OBJECTIVES: To investigate the association between urinary phthalate metabolite levels and indices for pulmonary function, and evaluate effect modification by genetic polymorphisms of oxidative-stress related genes, catalase (CAT), superoxide dismutase (SOD2), and myeloperoxidase (MPO) in elderly Koreans. METHODS: We conducted a panel study on 418 individuals over 60 years old in Seoul, Korea, and repeatedly measured urinary phthalate metabolite levels and ran pulmonary function tests. Genetic polymorphisms of CAT (rs769218, rs769217), SOD2 (rs4880, rs2758331, rs5746136) and MPO (rs2071409, rs7208693) were determined. Mixed effect model was used to investigate association of phthalate levels with pulmonary function indices and to examine the effect of CAT, SOD2 and MPO polymorphisms on the association. RESULTS: Inverse association was demonstrated between sum of mono-(2-ethyl-5-hydroxyhexyl) phthalate and mono-(2-ethyl-5-oxohexyl) phthalate (∑DEHP) levels and FEV1/FVC (ß=-0.632, p=0.0275) or FEF25-75 (ß=-0.077, p=0.025) after adjusting for age, months after previous measurements, sex, body mass index, cotinine, mean temperature and dew point. The effect of ∑DEHP on lung function was significant only in subjects with certain genotypes, and having all significant genotypes in three genes showed significant difference in the phthalate-pulmonary function association (FEV1/FVC: ß=-2.169, p=0.0032; FEF25-75: ß=-0.155, p=0.0103), while other combinations showed less estimate size without any significance. CONCLUSIONS: Urinary phthalate metabolites levels are associated with decreasing pulmonary function in elderly Koreans, and effect modification of certain CAT, SOD2 and MPO polymorphisms on the association is suggested.