Mee-Ri Lee

Urinary bisphenol A concentrations are associated with abnormal liver function in the elderly: a repeated panel study

Background Bisphenol A (4,40-isopropylidenediphenol, BPA) is known to adversely affect various organs. The liver is reported to be affected by BPA in animal studies. However, there are few studies in humans on the effects of BPA on the liver. Therefore, we evaluated the relationship between urinary BPA levels and liver function in elderly subjects using repeated measurements. Methods From 2008 to 2010, a total of 560 elderly subjects residing in Seoul were each evaluated up to three times. At the first visit, demographic data, environmental exposure and lifestyle information were obtained from a systemised questionnaire. At each visit, blood and urine samples were collected and stored for analysis. Linear mixed and GLIMMIX model analyses were performed after adjusting for age, sex, Body Mass Index, alcohol consumption, urinary cotinine concentrations, exercise frequency, and low-density lipoprotein cholesterol level. Results The mean urinary BPA concentration was 1.13 μg/g creatinine. Significant relationships were observed between urinary BPA and aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transferase after adjusting for potential confounders (p<0.05). When subjects were grouped according to urinary BPA concentrations divided by the median value, higher urinary BPA concentrations were associated with increased abnormal liver function (OR 2.66; 95% CI 1.15 to 5.90). Conclusions Community-level exposure to BPA was associated with abnormal liver function in the elderly, indicating that more stringent control of BPA is necessary to protect susceptible populations.

Modification of the association of bisphenol A with abnormal liver function by polymorphisms of oxidative stress-related genes

Some studies suggested oxidative stress as a possible mechanism for the relation between exposure to bisphenol A (BPA) and liver damage. Therefore, we evaluated modification of genetic polymorphisms of cyclooxygenase 2 (COX2 or PTGS2), epoxide hydrolase 1 (EPHX1), catalase (CAT), and superoxide dismutase 2 (SOD2 or MnSOD), which are oxidative stress-related genes, on the relation between exposure to BPA and liver function in the elderly. We assessed the association of visit-to-visit variations in BPA exposure with abnormal liver function by each genotype or haplotype after controlling for age, sex, BMI, alcohol consumption, exercise, urinary cotinine levels, and low density lipoprotein cholesterol using a GLIMMIX model. A significant association of BPA with abnormal liver function was observed only in participants with COX2 GG genotype at rs5277 (odds ratio (OR)=3.04 and p=0.0231), CAT genotype at rs769218 (OR=4.16 and p=0.0356), CAT CT genotype at rs769217 (OR=4.19 and p=0.0348), SOD2 TT genotype at rs4880 (OR=2.59 and p=0.0438), or SOD2 GG genotype at rs2758331 (OR=2.57 and p=0.0457). Moreover, we also found higher OR values in participants with a pair of G-G haplotypes for COX2 (OR=2.81 and p=0.0384), G-C-A haplotype for EPHX1 (OR=4.63 and p=0.0654), A-T haplotype for CAT (OR=4.48 and p=0.0245), or T-G-A haplotype for SOD2 (OR=2.91 and p=0.0491) compared with those with the other pair of haplotypes for each gene. Furthermore, the risk score composed of 4 risky pair of haplotypes showed interactive effect with BPA on abnormal liver function (p=0.0057). Our study results suggest that genetic polymorphisms of COX2, EPHX1, CAT, and SOD2 modify the association of BPA with liver function.

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.

Association between phthalate exposure and lower lung function in an urban elderly population: A repeated-measures longitudinal study

BACKGROUND Lung function is a major predictor of morbidity and mortality. Only a few studies have explored the association between phthalate exposure and lung function. OBJECTIVE To evaluate the association between phthalate exposure and lung function in the elderly. METHODS A total of 3 repeated-measures surveys were conducted in 559 elderly individuals aged ≥60 years in Seoul, Korea, at 1-year intervals (2012-2015). During each survey, urinary mono-(2-ethyl-5-hydrohexyl) phthalate (MEHHP) (geometric mean, 15.68 μg/L), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) (11.97 μg/L), and mono-n-butyl phthalate (MnBP) (2.09 μg/L) levels were measured; moreover, lung function tests and a structured questionnaire interview were performed. We constructed linear mixed models to assess the association between urinary phthalate metabolite levels and lung function. RESULTS A doubling of creatinine-adjusted urinary phthalate metabolite levels was inversely associated with forced expiratory volume in 1 s (L) (β = -0.01, 95% confidence interval [CI]: -0.02, 0.004 for MEHHP; β = -0.02, 95% CI: -0.03, -0.01 for MEOHP; β = -0.01, 95% CI: -0.03, -0.003 for MnBP) and forced vital capacity (L) (β = -0.02, 95% CI: -0.03, -0.001 for MEHHP; β = -0.02, 95% CI: -0.03, -0.004 for MEOHP; β = -0.02, 95% CI: -0.03, -0.001 for MnBP). A doubling of creatinine-adjusted MnBP levels was associated with increased rates of annual decline in forced vital capacity (L/year) (β = -0.01, 95% CI: -0.02, -0.001). CONCLUSIONS Urinary phthalate metabolite levels were associated with lower lung function and an increased rate of decline in lung function in an elderly population.

Blood lead levels, iron metabolism gene polymorphisms and homocysteine: a gene-environment interaction study

Objectives Homocysteine has been causally associated with various adverse health outcomes. Evidence supporting the relationship between lead and homocysteine levels has been accumulating, but most prior studies have not focused on the interaction with genetic polymorphisms. Methods From a community-based prospective cohort, we analysed 386 participants (aged 41–71 years) with information regarding blood lead and plasma homocysteine levels. Blood lead levels were measured between 2001 and 2003, and plasma homocysteine levels were measured in 2007. Interactions of lead levels with 42 genotyped single-nucleotide polymorphisms (SNPs) in five genes (TF, HFE, CBS, BHMT and MTR) were assessed via a 2-degree of freedom (df) joint test and a 1-df interaction test. In secondary analyses using imputation, we further assessed 58 imputed SNPs in the TF and MTHFR genes. Results Blood lead concentrations were positively associated with plasma homocysteine levels (p=0.0276). Six SNPs in the TF and MTR genes were screened using the 2-df joint test, and among them, three SNPs in the TF gene showed interactions with lead with respect to homocysteine levels through the 1-df interaction test (p<0.0083). Seven SNPs in the MTHFR gene were associated with homocysteine levels at an α-level of 0.05, but the associations did not persist after Bonferroni correction. These SNPs did not show interactions with lead levels. Conclusions Blood lead levels were positively associated with plasma homocysteine levels measured 4-6 years later, and three SNPs in the TF gene modified the association.