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eNOS gene polymorphisms modify the association of PM10 with oxidative stress
Authors:Jin Hee Kim  Yoon-Hyeong Choi  Sanghyuk Bae  Hye-Yin Park  Yun-Chul Hong
Affiliation:1. Institute of Environmental Medicine, Seoul National University Medical Research Center, Seoul 110-799, Republic of Korea;2. Department of Preventive Medicine, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea
Abstract:Previous studies have suggested that air pollution increases various health outcomes through oxidative stress and oxidative stress-related genes modify the relationship between air pollution and health outcomes. Therefore, we evaluated the effect of PM10 on the levels of malondialdehyde (MDA), oxidative stress biomarker, and the effect modification by genetic polymorphisms of eNOS, oxidative stress-related gene, in the 560 Korean elderly. We obtained urine samples repeatedly from participants during five medical examinations between 2008 and 2010 and all ambient air pollutant concentration data from the Korea National Institute of Environmental Research air quality monitoring system. We measured urinary levels of MDA to assess oxidative stress and genotyped eNOS (rs1799983, rs2853796, and rs7830). Mixed-effect model was used to estimate the effect of PM10 on the level of oxidative stress biomarker and their modification by genotypes. PM10 showed apparent positive effect on MDA level after adjusting for age, sex, BMI, cotinine level, temperature, dew point, levels of SO2, O3, NO2, and CO, and season (p = 0.0133). Moreover, the association of PM10 with MDA was found only in participants with eNOS GG genotype for rs1799983 (p = 0.0107), TT genotype for rs2853796 (p = 0.0289), or GT genotype for rs7830 (p = 0.0158) and in participants with a set of risky haplotypes (GTT, GTG, GGT, and TGT) (p = 0.0093). Our results suggest that PM10 affect oxidative stress in the elderly and eNOS genotype affect the oxidative stress level in regard of exposure to PM10.
Keywords:PM10, particulate matter less than 10   μm   MDA, malondialdehyde   eNOS, endothelial nitric oxide synthase   KEEPs, Korean Elderly Environmental Panel study   PCR, polymerase chain reaction   LD, linkage disequilibrium   D&prime  , relative disequilibrium   HWE, Hardy&ndash  Weinberg equilibrium   BMI, body mass index   IQR, inter-quartile range
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