Prospective findings from the Dongfeng-Tongji cohort: Exposure to various metals, the expression of microRNA-4286, and the incidence of acute coronary syndrome.

Mounting evidence suggests that metal/metalloid exposure is related to the adverse health effects. Our prior investigation revealed a positive relation between the plasma level of microRNA-4286 (miR-4286) and an increased risk of developing acute coronary syndrome (ACS). However, it is a lack of studies evaluating the connection between metal/metalloid exposure and miRNA expression on ACS. In the prospective Dongfeng-Tongji cohort, we performed a nested case-control study. A total of 480 ACS and 480 controls were carefully selected based on similar age, sex, and blood collection time. Using inductively coupled plasma mass spectrometry, we assessed the plasma concentrations of 24 different metals. Quantitative real-time polymerase chain reaction was used to analyze the plasma miR-4286. We examined the relations of plasma metals with miR-4286 levels, the incidence of ACS, and the potential interactions. Using the multivariate conditional logistic regression models, we observed that the adjusted odds ratios (95% confidence intervals [CI]) for incident ACS were 1.79 (1.03, 3.12; P-trend = 0.03), 0.60 (0.41, 0.87; P-trend = 0.008), and 0.66 (0.46, 0.93; P-trend = 0.02), when comparing the extreme tertiles of aluminum, rubidium, and selenium, respectively. There was a relation between the concentration of rubidium in plasma and a decrease in the level of plasma miR-4286 (percent difference [95% CI]: -13.36% [-22.74%, -2.83%]; P-trend = 0.01). Both multiplicative (P interaction = 0.009) and additive interactions (relative excess risk due to interaction [95% CI]: 0.82 [0.59, 1.06]) were noted in our observation regarding the relationship between plasma aluminum and miR-4286 in incident ACS. The findings indicated that plasma aluminum was positively while plasma rubidium and selenium were negatively linked to an increased risk of developing ACS. Plasma aluminum exposure and plasma miR-4286 expression might synergistically affect the incident ACS risk. Controlling aluminum exposure was important for ACS prevention, especially for individuals with high expression of plasma miR-4286.

Associations of Plasma Metabolites With Risks of Incident Stroke and Its Subtypes in Chinese Adults.

BACKGROUND: Metabolomics studies have identified various metabolic markers associated with stroke risk, yet much uncertainty persists regarding heterogeneity in these associations between different stroke subtypes. We aimed to examine metabolic profiles associated with incident stroke and its subtypes in Chinese adults. METHODS AND RESULTS: We performed a nested case-control study within the Dongfeng-Tongji cohort, including 1029 and 266 incident cases of ischemic stroke (IS) and hemorrhagic stroke (HS), respectively, with a mean follow-up period of 6.1±2.3 years. Fifty-five metabolites in fasting plasma were measured by ultra-high-performance liquid chromatography-mass spectrometry. We examined the associations of metabolites with the risks of total stroke, IS, and HS, with a focus on the comparison of associations of plasma metabolite with IS and HS, using conditional logistic regression. We found that increased levels of asymmetrical/symmetrical dimethylarginine and glutamate were significantly associated with elevated risk of total stroke (odds ratios and 95%, 1.20 [1.08-1.34] and 1.22 [1.09-1.36], respectively; both Benjamini-Hochberg-adjusted P <0.05). When examining stroke subtypes, asymmetrical/symmetrical dimethylarginine was nominally associated with both IS and HS (odds ratios [95% CIs]: 1.16 [1.03-1.31] and 1.39 [1.07-1.81], respectively), while glutamate was associated with only IS (odds ratios [95% CI]: 1.26 [1.11-1.43]). The associations of glutamate with IS risk were significantly stronger among participants with hypertension and diabetes than among those without these diseases (both P for interaction <0.05). CONCLUSIONS: This study validated the positive associations of asymmetrical/symmetrical dimethylarginine and glutamate with stroke risk, mainly that of IS, in a Chinese population, and revealed a novel unanimous association of with both IS and HS. Our findings provided potential intervention targets for stroke prevention.

Particulate matter pollution, polygenic risk score and mosaic loss of chromosome Y in middle-aged and older men from the Dongfeng-Tongji cohort study.

Mosaic loss of chromosome Y (mLOY) is the most common somatic alteration as men aging and may reflect genome instability. PM exposure is a major health concern worldwide, but its effects with genetic factors on mLOY has never been investigated. Here we explored the associations of PM2.5 and PM10 exposure with mLOY of 10,158 males measured via signal intensity of 2186 probes in male-specific chromosome-Y region from Illumina array data. The interactive and joint effects of PM2.5 and PM10 with genetic factors and smoking on mLOY were further evaluated. Compared with the lowest tertiles of PM2.5 levels in each exposure window, the highest tertiles in the same day, 7-, 14-, 21-, and 28-day showed a 0.005, 0.006, 0.007, 0.007, and 0.006 decrease in mLRR-Y, respectively (all P < 0.05), with adjustment for age, BMI, smoking pack-years, alcohol drinking status, physical activity, education levels, season of blood draw, and experimental batch. Such adverse effects were also observed in PM10-mLOY associations. Moreover, the unweighted and weighted PRS presented significant negative associations with mLRR-Y (both P < 0.001). Participants with high PRS and high PM2.5 or PM10 exposure in the 28-day separately showed a 0.018 or 0.019 lower mLRR-Y level [ß (95 %CI) = -0.018 (-0.023, -0.012) and - 0.019 (-0.025, -0.014), respectively, both P < 0.001], when compared to those with low PRS and low PM2.5 or PM10 exposure. We also observed joint effects of PM with smoking on exacerbated mLOY. This large study is the first to elucidate the impacts of PM2.5 exposure on mLOY, and provides key evidence regarding the interactive and joint effects of PM with genetic factors on mLOY, which may promote understanding of mLOY development, further modifying and increasing healthy aging in males.