Yoon-Hyeong Choi

eNOS gene polymorphisms modify the association of PM10 with oxidative stress

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 PM(10) 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 PM(10) on the level of oxidative stress biomarker and their modification by genotypes. PM(10) showed apparent positive effect on MDA level after adjusting for age, sex, BMI, cotinine level, temperature, dew point, levels of SO(2), O(3), NO(2), and CO, and season (p=0.0133). Moreover, the association of PM(10) 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 PM(10) affect oxidative stress in the elderly and eNOS genotype affect the oxidative stress level in regard of exposure to PM(10).

CYP1A1 genetic polymorphism and polycyclic aromatic hydrocarbons on pulmonary function in the elderly: haplotype-based approach for gene-environment interaction.

Lung function may be impaired by environmental pollutants not only acting alone, but working with genetic factors as well. Few epidemiologic studies have been conducted to explore the interplay of polycyclic aromatic hydrocarbons (PAHs) exposure and genetic polymorphism on lung function in the elderly. For genetic polymorphism, haplotype is considered a more informative unit than single nucleotide polymorphism markers. Therefore, we examined the role of haplotype based-CYP1A1 polymorphism in the effect of PAHs exposure on lung function in 422 participants from a community-based panel of elderly adults in Seoul, Korea. Linear mixed effect models were fit to evaluate the association of PAH exposure markers (urinary 1-hydroxypyrene and 2-naphthol) with FVC, FEV₁, FEV₁/FVC, and FEF₂₅₋₇₅, and then the interaction with CYP1A1 haplotype constructed from three single nucleotide polymorphisms of the gene (rs4646421/rs4646422/rs1048943). Urinary 1-hydroxypyrene levels were inversely associated with FEV₁/FVC (p<0.05), whereas urinary 2-naphthol levels failed to show associations with lung function. Urinary 1-hydroxypyrene was significantly associated with decrease in FEV₁/FVC among participants with rs4646421 variants (CT+TT), rs4646422 wild-type (GG), and rs1048943 wild-type (AA). At least one TGA haplotype predicted a 0.88% (95% confidence interval, 0.31-1.45%) reduction in FEV₁/FVC with an interquartile range increase in 1-hydroxypyrene, whereas no relationship was observed in participants without TGA haplotype (p for interaction=0.045). Similar patterns were also observed in FEF₂₅₋₇₅. We did not find any main effects of CYP1A1 genetic polymorphisms on lung functions. Our findings suggest that PAH exposure producing 1-hydroxypyrene as a metabolite compromises lung function in the elderly, and that haplotype-based CYP1A1 polymorphism modifies the risk.

Urinary benzene metabolite and insulin resistance in elderly adults.

BACKGROUNDnBenzene is a volatile organic compound present in traffic-related and indoor air pollution. It is of particular concern since it is known to induce oxidative stress, which can affect insulin resistance (IR). We therefore examined the association between exposure to environmental benzene and IR in the elderly.nnnSTUDY DESIGNnBetween 2008 and 2010, benzene metabolite levels (urinary trans,trans-muconic acid (t,t-MA)) and homeostatic model assessment index (HOMA-IR) were repeatedly measured in 505 adults aged ≥60 years. Linear mixed-effect models and marginal logistic models were used to evaluate associations of t,t-MA concentration with HOMA-IR score and elevated IR, defined as HOMA-IR ≥2.6.nnnRESULTSnAfter adjustment for sociodemographic and behavioral factors, environmental co-exposures, and metabolic conditions, quartile levels of urinary t,t-MA demonstrated a dose-dependent association with elevated IR (p-trend<0.001) and the level of oxidative stress estimated by urinary malondialdehyde (p-trend<0.001). As compared to the lowest quartile, the upper quartiles of t,t-MA (t,t-MA concentration >0.017mg/g CR) were associated with elevated IR [odds ratio=Q2: 2.00 (95% confidence interval (CI): 1.16-3.46); Q3: 3.33 (95% CI: 1.90-5.84); Q4: 2.07 (95% CI: 1.02-4.22)].nnnCONCLUSIONnUrinary benzene at levels currently observed in the urban elderly population is associated with IR, independent of traditional risk factors. Reduction of community-level exposure to benzene is therefore important for the effective prevention of IR in older adults.

Association of urinary 3-phenoxybenzoic acid levels with self-reported depression symptoms in a rural elderly population in Asan, South Korea.

Objectives: This study aimed to evaluate the association between presence of depression symptoms and the exposure level to insecticides among aged population in rural area, determined via measured levels of urinary 3-phenoxybenzoic acid (3-PBA), after controlling for socioeconomic confounding factors. Methods: Using a cross-sectional study design, we randomly recruited participants for our study (161 male and 239 female) from rural areas of Asan, Chungnam, Korea. Environmental risk factor exposure was assessed using a questionnaire, and gas chromatography- mass spectrometry was used to analyze urinary 3-PBA levels. We used a logistic regression analysis to assess the association of urinary 3-PBA levels with the presence of self-reported depression symptoms. Results: After controlling for creatinine levels, the median (interquartile range) concentration of 3-PBA was approximately 1.5 times (p<0.05) higher among female (1.54 [0.90 to 2.35]) μg/g) than among male (1.06 [0.64 to 1.81] μg/g). Our study found that among female participants, the unit increase in 3-PBA levels exhibited a likely positive association (odds ratio, 1.12; 95% confidence interval, 1.00 to 1.25) with an increased risk of presence of self-reported depression symptoms, after adjusting for socioeconomic insurance type, daily physical condition, marital status, smoking status, and age. Conclusions: Given our finding of a potential association between the presence of selfreported depression symptoms and 3-PBA levels, precautions should be considered to minimize exposure to insecticides and thus protect the health of aged residents in rural areas.