50 research outputs found

    Genome-wide association study on serum alkaline phosphatase levels in a Chinese population

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    Background: Serum alkaline phosphatase (ALP) is a complex phenotype influenced by both genetic and environmental factors. Recent Genome-Wide Association Studies (GWAS) have identified several loci affecting ALP levels; however, such studies in Chinese populations are limited. We performed a GWAS analyzing the association between 658,288 autosomal SNPs and serum ALP in 1,461 subjects, and replicated the top SNPs in an additional 8,830 healthy Chinese Han individuals. The interactions between significant locus and environmental factors on serum ALP levels were further investigated. Results: The association between ABO locus and serum ALP levels was replicated (P = 2.50 × 10-21, 1.12 × 10-56 and 2.82 × 10-27 for SNP rs8176720, rs651007 and rs7025162 on ABO locus, respectively). SNP rs651007 accounted for 2.15% of the total variance of serum ALP levels independently of the other 2 SNPs. When comparing our findings with previously published studies, ethnic differences were observed across populations. A significant interaction between ABO rs651007 and overweight and obesity was observed (FDR for interaction was 0.036); for individuals with GG genotype, those with normal weight and those who were overweight or obese have similar serum ALP concentrations; minor allele A of rs651007 remarkably reduced serum ALP levels, but this effect was attenuated in overweight and obese individuals. Conclusions: Our findings indicate that ABO locus is a major determinant for serum ALP levels in Chinese Han population. Overweight and obesity modifies the effect of ABO locus on serum ALP concentrations

    The 5p15.33 Locus Is Associated with Risk of Lung Adenocarcinoma in Never-Smoking Females in Asia

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    Genome-wide association studies of lung cancer reported in populations of European background have identified three regions on chromosomes 5p15.33, 6p21.33, and 15q25 that have achieved genome-wide significance with p-values of 10−7 or lower. These studies have been performed primarily in cigarette smokers, raising the possibility that the observed associations could be related to tobacco use, lung carcinogenesis, or both. Since most women in Asia do not smoke, we conducted a genome-wide association study of lung adenocarcinoma in never-smoking females (584 cases, 585 controls) among Han Chinese in Taiwan and found that the most significant association was for rs2736100 on chromosome 5p15.33 (p = 1.30×10−11). This finding was independently replicated in seven studies from East Asia totaling 1,164 lung adenocarcinomas and 1,736 controls (p = 5.38×10−11). A pooled analysis achieved genome-wide significance for rs2736100. This SNP marker localizes to the CLPTM1L-TERT locus on chromosome 5p15.33 (p = 2.60×10−20, allelic risk = 1.54, 95% Confidence Interval (CI) 1.41–1.68). Risks for heterozygote and homozygote carriers of the minor allele were 1.62 (95% CI; 1.40–1.87), and 2.35 (95% CI: 1.95–2.83), respectively. In summary, our results show that genetic variation in the CLPTM1L-TERT locus of chromosome 5p15.33 is directly associated with the risk of lung cancer, most notably adenocarcinoma

    Association of plasma IL-6 and Hsp70 with HRV at different levels of PAHs metabolites.

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    Exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with reduced heart rate variability (HRV), a strong predictor of cardiovascular diseases, but the mechanism is not well understood.We hypothesized that PAHs might induce systemic inflammation and stress response, contributing to altered cardiac autonomic function.HRV indices were measured using a 3-channel digital Holter monitor in 800 coke oven workers. Plasma levels of interleukin-6 (IL-6) and heat shock protein 70 (Hsp70) were determined using ELISA. Twelve urinary PAHs metabolites (OH-PAHs) were measured by gas chromatography-mass spectrometry.We found that significant dose-dependent relationships between four urinary OH-PAHs and IL-6 (all Ptrend<0.05); and an increase in quartiles of IL-6 was significantly associated with a decrease in total power (TP) and low frequency (LF) (Ptrend = 0.014 and 0.006, respectively). In particular, elevated IL-6 was associated in a dose-dependent manner with decreased TP and LF in the high-PAHs metabolites groups (all Ptrend<0.05), but not in the low-PAHs metabolites groups. No significant association between Hsp70 and HRV in total population was found after multivariate adjustment. However, increased Hsp70 was significantly associated with elevated standard deviation of NN intervals (SDNN), TP and LF in the low-PAHs metabolites groups (all Ptrend<0.05). We also observed that both IL-6 and Hsp70 significantly interacted with multiple PAHs metabolites in relation to HRV.In coke oven workers, increased IL-6 was associated with a dose-response decreased HRV in the high-PAHs metabolites groups, whereas increase of Hsp70 can result in significant dose-related increase in HRV in the low-PAHs metabolites groups

    Atomistic and Coarse-Grained Molecular Dynamics Simulation of a Cross-Linked Sulfonated Poly(1,3-cyclohexadiene)-Based Proton Exchange Membrane

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    Atomistic and coarse-grained (CG) molecular dynamics (MD) simulations were conducted for a cross-linked and sulfonated poly­(1,3-cyclohexadiene) (xsPCHD) hydrated membrane with λ­(H<sub>2</sub>O/HSO<sub>3</sub>) = 10 and 20. From the atomistic level simulation results, nonbonded pair correlation functions (PCFs) of water–water, water–H<sub>3</sub>O<sup>+</sup> ion, H<sub>3</sub>O<sup>+</sup>–H<sub>3</sub>O<sup>+</sup>, polymer–water, and polymer–H<sub>3</sub>O<sup>+</sup> ion pairs were obtained and studied. The water self-diffusivity and H<sub>3</sub>O<sup>+</sup> vehicular self-diffusivity were also obtained. Membrane structure was further studied at CG level using a multiscale modeling procedure. Nonbonded PCFs of polymer–polymer pairs were obtained from atomistic simulation of hydrated membrane with λ = 10 and 20. Two sets of CG nonbonded potentials were then parametrized to the PCFs using the iterative Boltzmann inversion (IBI) method. The CGMD simulations of xsPCHD chains using potentials from above method satisfactorily reproduced the polymer–polymer PCFs from atomistic MD simulation of hydrated membrane system at each hydration level. The transferability of above two set of CG potentials was further tested through CGMD simulation of hydrated membrane at an intermediate hydration level (λ = 15). Limited transferability was observed, presumably due to the use of an implicit solvent. Using an analytical theory, proton conductivity was calculated and compared with that from experimental measurement under similar conditions. Good agreement was obtained using inputs from both atomistic and CG simulation. This study provides a molecular level understanding of relationship between membrane structure and water and H<sub>3</sub>O<sup>+</sup> ion transport in the xsPCHD membrane

    Hematological Effects and Benchmark Doses of Long-Term Co-Exposure to Benzene, Toluene, and Xylenes in a Follow-Up Study on Petrochemical Workers

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    Benzene, toluene, and xylenes (BTX) commonly co-exist. Exposure to individual components and BTX-rich mixtures can induce hematological effects. However, the hematological effects of long-term exposure to BTX are still unclear, and respective reference levels based on empirical evidence should be developed. We conducted a follow-up study in BTX-exposed petrochemical workers. Long-term exposure levels were quantified by measuring cumulative exposure (CE). Generalized weighted quantile sum (WQS) regression models and Benchmark Dose (BMD) Software were used to evaluate their combined effects and calculate their BMDs, respectively. Many hematologic parameters were significantly decreased at the four-year follow-up (p 0.010, Ptrend Pinteraction Ptrend for WQS indices 3 × year, respectively. Our study demonstrated the hematological effects of long-term BTX co-exposure and developed 8h-RELs of about 0.01 ppm based on their hematological effects