Associations among global long interspersed nuclear element-1 DNA methylation, metal exposure, and chronic kidney disease.

Long interspersed nuclear element-1 (LINE-1) methylation serves as an indicator of global DNA methylation. This study explored the correlation between LINE-1 methylation and chronic kidney disease (CKD). We also evaluated whether LINE-1 methylation could modify the association between CKD and metal exposure. A total of 213 patients with clinically defined CKD, without hemodialysis and 416 age and sex matched controls were recruited. Levels of LINE-1 methylation, total urinary arsenic, blood lead, blood cadmium, and plasma selenium were assessed. The results reveal a positive association between LINE-1 methylation and CKD, with an odds ratio (OR) of 5.30 (95% confidence interval: 2.81 to 9.99). Total urinary arsenic and blood cadmium concentrations were positively related with LINE-1 methylation. This study was the first to observe that low plasma selenium, high blood cadmium, and high blood lead levels significantly and additively interact with increased LINE-1 methylation to increase the OR of CKD. Additionally, high LINE-1 methylation interacted multiplicatively with low plasma selenium to increase the OR of CKD (p < 0.001). This study highlighted the significant association between LINE-1 hypermethylation and CKD. Furthermore, the results demonstrate that LINE-1 methylation can interact with high blood cadmium or low plasma selenium to affect CKD risk.

Global DNA methylation and the association between metal exposure and chronic kidney disease.

Introduction: Prior studies indicate that exposure to metals may alter DNA methylation. Evidence also shows that global DNA methylation is associated with chronic kidney disease (CKD). This study aimed to examine the association between CKD and 5-methyl-2-deoxycytidine (5mdC, %), a marker of global DNA methylation, and to evaluate the interaction between metal exposures and 5mdC (%) on CKD. We also explored the mediation effect of 5mdC (%) on the association between metal exposures and renal function (i.e., estimated glomerular filtration rate, eGFR). Methods: A total of 218 CKD patients and 422 controls were recruited in this case-control study. 5mdC (%), concentrations of blood lead and cadmium, plasma selenium, and total urinary arsenic were measured. CKD cases were clinically defined among patients with eGFR <60 mL/min/1.73 m2 for at least 3 months and without hemodialysis. Odds ratio (OR) and 95% confidence interval (CI) were estimated by logistic regression models to examine the association between metal exposures, 5mdC (%), and CKD, adjusted for confounders. Multivariable linear regression models were used to examine associations between metal exposures, 5mdC (%), and eGFR. Results and Discussion: CKD cases compared to controls had 6.06-fold (95% CI: 3.11-11.81) higher odds of having high blood cadmium and high 5mdC (%) levels. A positive interaction on an additive scale was identified between blood cadmium and 5mdC (%) on CKD. Cases compared to controls had 4.73-fold (95% CI: 2.65-8.45) higher odds of having low plasma selenium and high 5mdC (%) levels; and a significant multiplicative interaction between plasma selenium and 5mdC (%) on CKD was observed. In addition, we found that blood lead and cadmium concentrations were positively associated, while plasma selenium concentrations were inversely associated, with 5mdC (%). The associations of blood lead and plasma selenium with eGFR were partially mediated by 5mdC (%). Our results suggest that 5mdC (%) may interact with plasma selenium and blood cadmium to influence the risk of CKD. The 5mdC (%) also potentially mediates the associations between exposure to metals and renal function.

Chronic Kidney Disease: Interaction of Adiponectin Gene Polymorphisms and Diabetes.

Adiponectin is an adipokine multipeptide hormone with insulin-sensitizing; anti-atherosclerotic; and anti-inflammatory properties. Chronic kidney disease (CKD) may be associated with low adiponectin. The adiponectin gene ADIPOQ is thought to be the only major gene responsible for plasma adiponectin levels; which are associated with diabetes and diabetic nephropathy. The purpose of this study was to investigate the association between ADIPOQ polymorphism and CKD. In addition; the combined effects of ADIPOQ polymorphism and diabetes and levels of total urinary arsenic and blood cadmium on CKD were also explored. This study included 215 CKD patients and 423 age-sex matched controls. The ADIPOQ polymorphisms were determined using the Agena Bioscience Mass ARRAY System. The levels of blood cadmium and urinary arsenic species were measured. The ADIPOQ rs182052 GA/AA genotype had a marginally lower odds ratio (OR) for CKD than the GG genotype. The OR (95% confidence interval; CI) was 16.33 (5.72-46.66) of CKD in subjects carrying the ADIPOQ rs182052 GG genotype and diabetes compared to non-diabetes subjects carrying the ADIPOQ rs182052 GA/AA genotype; the interaction term had p = 0.015; and the synergy index was 6.64 (1.81-24.36) after multivariate adjustment. A significant interaction of diabetes and ADIPOQ rs1501299 risk genotype increased the OR of CKD after multivariate adjustment with a synergy index of 0.31 (0.11-0.86) and a multiplicative interaction with p = 0.001. These results suggest that ADIPOQ rs182052 and rs1501299 risk genotypes may significantly modify the association between diabetes and CKD but not the association between total urinary arsenic and blood cadmium and CKD.

Chronic Kidney Disease: Combined Effects of Gene Polymorphisms of Tissue Inhibitors of Metalloproteinase 3, Total Urinary Arsenic, and Blood Lead Concentration.

The tissue inhibitor of metalloproteinase 3 (TIMP3) is known to be an anti-fibrotic factor. Arsenic, lead, and cadmium exposure and selenium intake may affect TIMP3 expression. The downregulation of TIMP3 expression is related to kidney fibrosis. Genotypes of TIMP3 are related to hypertension and cardiovascular diseases. Therefore, this study explored whether TIMP3 polymorphism is associated with hypertension-related chronic kidney disease (CKD). In addition, the combined effects of TIMP3 polymorphism and total urinary arsenic, blood lead and cadmium, and plasma selenium concentrations on CKD, were investigated. This was a case-control study, with 213 CKD patients and 423 age- and sex-matched controls recruited. Polymerase chain reaction-restriction fragment length polymorphism was used to determine TIMP3 gene polymorphisms. The concentrations of urinary arsenic species, plasma selenium, and blood lead and cadmium were measured. The odds ratio (OR) of CKD in the TIMP3rs9609643 GA/AA genotype was higher than that of the GG genotype at high levels of total urinary arsenic and blood lead; the OR and 95% confidence interval (CI) were 0.57 (0.31-1.05) and 0.52 (0.30-0.93), respectively, after multivariate adjustment. High blood lead levels tended to interact with the TIMP3rs9609643 GG genotype to increase the OR of CKD, and gave the highest OR (95% CI) for CKD of 5.97 (2.60-13.67). Our study supports a possible role for the TIMP3rs9609643 risk genotype combined with high total urinary arsenic or with high blood lead concentration to increase the OR of CKD.

Enhanced Risk of Osteoporotic Fracture in Patients with Sarcopenia: A National Population-Based Study in Taiwan.

Sarcopenia is a progressive and generalized skeletal muscle disorder associated with poor health outcomes in older adults. However, its association with the risk of fracture risk is yet to be clarified. Therefore, this study aimed to assess the incidence and consequence of osteoporosis-related fractures among patients with sarcopenia in Taiwan. A retrospective, population-based study on 616 patients with sarcopenia, aged >40 years, and 1232 individuals without sarcopenia was conducted to evaluate claims data from Taiwan's National Health Insurance Research Database collected in the period January 2000−December 2013. The incidence rate of osteoporosis-related fracture was 18.13 and 14.61 per 1000 person years in the patients with sarcopenia and comparison cohort, respectively. Patients with sarcopenia had a greater osteoporotic fracture risk (adjusted hazard ratio [HR] 2.11; 95% confidence interval [CI] 1.47−3.04) after correcting for possible confounding. Additionally, females showed statistically significant correlations of sarcopenia with osteoporosis-related fracture risk (HR 1.53; CI 0.83−2.8 for males and HR 2.40, CI 1.51−3.81 for females). During this retrospective study on the fracture risk in Taiwan, an adverse impact of sarcopenia was observed, which substantiates the need to work toward sarcopenia prevention and interventions to reverse fracture susceptibility in patients with sarcopenia.

Dual trajectories of loneliness and depression and their baseline correlates over a 14-year follow-up period in older adults: Results from a nationally representative sample in Taiwan.

AIMS: To explore the codevelopment between loneliness and depression in older adults, and to identify its potential baseline individual, family and extrafamilial correlates. BACKGROUND: The number of older adults around the world has steadily increased over the last decades. Later life is a particularly vulnerable life stage due to multiple unfavourable conditions, and mental health in this stage appears to become an inescapable issue. Previous research has found the cross-sectional association between loneliness and depression, but their codevelopment has been understudied. Therefore, exploring the codevelopment and its correlates has significant implications for prevention and healthcare professionals. DESIGN: A longitudinal follow-up study. METHODS: The study used nationally representative data over a 14-year follow-up period from the Taiwan Longitudinal Study on Ageing focused on Taiwanese aged 60 years and above (n = 4049). Group-based trajectory modelling, group-based dual-trajectory modelling and multinomial logistic regression were the primary analytical methods. RESULTS: We identified three distinct dual trajectories of loneliness and depression: longitudinal low-frequency lonely depressed (29.3%), longitudinal moderate-frequency lonely depressed (59.4%) and longitudinal high-frequency lonely depressed (11.3%). After considering several demographic and background characteristics, difficulty in physical functioning, number of physical symptoms and diseases, sleep quality and number of child deaths were found to be significantly associated. CONCLUSION: Across the three identified dual-trajectory groups, they all showed a stable loneliness frequency pattern over time; however, the moderate-frequency group and high-frequency group both had a trajectory of increasing depression. It seems that depression tends to change over time in a worsening direction, especially for those with a certain frequency of loneliness. Furthermore, differences in individual and family correlates were found across the groups. IMPLICATIONS FOR PRACTICE: Interventions focusing on the specific factors may help hinder coexisting loneliness and depression, and have implications for developing health promotion strategies and chronic disease care plans.