Influence of Genetic Polymorphisms on the Association between Phthalate Exposure and Pulmonary Function in Elderly Koreans

phthalates;pulmonary function;genetic polymorphisms;elderly

의과대학 의학과 ;

University:서울대학교 대학원

关键词: phthalates;    pulmonary function;    genetic polymorphisms;    elderly;   

Others  :  http://s-space.snu.ac.kr/bitstream/10371/132516/1/000000004902.pdf

美国|英语

来源: Seoul National University Open Repository

【 摘 要 】

Introduction: Phthalates are prevalent environmental exposure chemical that have raised concern regarding their 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. The purpose of current study was 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 and rs769217), SOD2 (rs4880, rs2758331, and rs5746136) and MPO (rs2071409, rs7208693) were determined. Mixed effect model was used to investigate association of urinary phthalate metabolite levels with indices for pulmonary function 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 (P=0.0275) or FEF25-75 (P=0.002) after adjusting for age, number of months past after each 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 GG genotype of CAT rs769218 and CC genotype of CAT rs769217, TT genotype of SOD2 rs4880 and CC genotype of SOD2 rs2758331, AA genotype of MPO rs2071409 and GG genotype of MPO rs7208693. Having all significant genotypes in three genes compared to other combinations showed significant difference in the phthalate-pulmonary function association (p-value for interaction: 0.0176 for ∑DEHP and FEV1/FVC, 0.0663 and FEF25-75).Conclusions: In conclusion, we found urinary phthalate metabolites levels associated with decreasing pulmonary function in elderly Koreans, and suggested the effect modification of certain CAT, SOD2 and MPO polymorphisms on the phthalates-lung function association.