Genetic associations with coronary heart disease: Meta-analyses of 12 candidate genetic variants

Aims

The aim of this study was to evaluate the combined contribution of 12 genetic variants to the risk of coronary heart disease (CHD).

Methods

Through a comprehensive literature search for genetic variants involved in the CHD association study, we harvested a total of 10 genes (12 variants) for the current meta-analyses. These genes consisted of GPX1 (rs1050450), PPARD (rs2016520), ALOX15 (rs34210653), SELPLG (rs2228315), FCGR2A (rs1801274), CCL5 (rs2107538), CYP1A1 (rs4646903), TP53 (rs1042522), CX37 (rs1764391), and PECAM1 (rs668, rs12953, and rs1131012).

Results

A total of 45 studies among 23,314 cases and 28,430 controls were retrieved for the meta-analyses of 12 genetic variants. The results showed a significant association between the GPX1 rs1050450 polymorphism and CHD (odd ratio (OR) = 1.61, 95% confidence interval (CI) = 1.25–2.07, P = 0.0002). Other meta-analyses of the rest 11 variants suggested a lack of association with the risk of CHD.

Conclusion

Our results confirmed that GPX1 rs1050450 was associated with susceptibility to CHD in Chinese and Indian populations.     

Intraspecific molecular phylogeny and phylogeography of the Meriones meridianus (Rodentia: Cricetidae) complex in northern China reflect the processes of desertification and the Tianshan Mountains uplift

The phylogeographical patterns and demographic history of mitochondrial DNA (cytochrome b, N = 327; D‐loop, N = 252) and nuclear DNA (IRBP gene, N = 235) haplotypes were studied for the Meriones meridianus complex in northern China, a desert‐dwelling gerbil species complex. The phylogenetic analyses, which were performed on the separate and combined (mitochondrial + nuclear) datasets, revealed two divergent clades (Clade A and Clade B) corresponding to distinct geographical regions. Clade A contained the haplotypes found mostly in individuals from the Tianshan Mountains area. Clade B contained haplotypes from populations located in other deserts in northern China. The divergence times indicated that the history of the M. meridianus complex was influenced by the uplift of the Tianshan Mountains and climate‐induced habitat fluctuations. In the Pleistocene, the expansion of forests and grasslands during interglacial period led to the isolation of the M. meridianus complex, which preferred to inhabit deserts. Hence, long geological isolation and the M. meridianus complex adaptation to local ecological conditions led to its genetic divergence. Clade A had long‐lasting demographic stability, most likely because the populations of this clade remained in a stable desert environment for a long time. However, the extension of other deserts and disappearance of palaeolakes during the last glacial period resulted in demographic expansion of Clade B. Furthermore, our genetic data indicated that two subspecies may exist within the M. meridianus complex. © 2013 The Linnean Society of London, Biological Journal of the Linnean Society, 2013, 110 , 362–383.     

Evaluation of Antibody-Dependent Enhancement of SARS-CoV Infection in Rhesus Macaques Immunized with an Inactivated SARS-CoV Vaccine

正Dear Editor,In 2003,severe acute respiratory syndrome coronavirus(SARS-CoV)emerged in Guangdong Province,China,infected more than 8000 individuals,and resulted in a 10%mortality rate(Rota et al.2003).Later,in 2012,a novel CoV,Middle East respiratory syndrome coronavirus(MERS-CoV),was isolated from the sputum of a man in Saudi Arabia(Perl et al.2014).Notably,MERS-CoV     

Effects of patient-controlled analgesia with hydromorphone or sufentanil on postoperative pulmonary complications in patients undergoing thoracic surgery: a quasi-experimental study

Objective

To compare the analgesic effects of patient-controlled intravenous analgesia (PCA) with hydromorphone and sufentanil after thoracic surgery on postoperative pulmonary complications (PPCs).

Methods

A total of 142 patients who were scheduled for thoracic surgery were randomly allocated to receive PCA with hydromorphone (group A: experimental group): hydromorphone 0.2?mg/kg?+?dezocine 0.5?mg/kg?+?ramosetron 0.6?mg diluted with normal saline to 200?mL; or with sufentanil (group B: control group): sufentanil 3.0μg/kg?+?dezocine 0.5?mg/kg?+?ramosetron 0.6?mg diluted with normal saline to 200?mL. The parameters of intravenous analgesia pump were set as background dose 4?ml/h, PCA dose 1?mL, locking time 15?min. Pain NRS (numerical rating scale), Ramsay sedation score, nausea or vomiting score were evaluated at 0?h, 6?h, 12?h, 24?h, 48?h after operation. The cases of PPCs (atelectasis, pulmonary infection, respiratory failure), CRP (C-reaction protein) and inflammatory cells (white cell count and percentage of neutrophils) and blood gas analysis at 12?h after operation, length of ICU and postoperative stay were recorded for each patient.

Results

Data of 136 patients were analyzed. Compared with group B (4[IQR:2,2]), the pain NRS in group A (2[IQR:4,4]) was significantly lower at 6?h after operation (P?=?0.000). The CRP in group A (69.79?±?32.13?mg/L) were lower than group B (76.76?±?43.42?mg/L) after operation, but the difference was not significant (P?=?0.427). No difference of nausea or vomiting was found between group A (7.3%) and group B (5.8%) postoperatively (P?=?0.999). The PPCs were happened in 11 patients in group A (16.2%) and 22 patients in group B (32.4%) and the difference between two groups was significant (P?=?0.027). Seven patients in group A (10.3%) and eighteen patients in group B (26.5%) had clinical evidence of pneumonia and the difference between two groups was significant (P?=?0.014). The length of ICU and postoperative stay in group A were 2.73?h and 1.82?days less than group B respectively but the differences were not significant (P?=?0.234, P?=?0.186 respectively).

Conclusion

Compared with sufentanil, hydromorphone may provide better postoperative analgesic effect with less pulmonary complications for patients undergoing thoracic surgery, and it may accelerate patients’ rehabilitation.

Trial registration

Randomized Controlled Trials ChiCTR1800014282c. Registered 3 January 2018.

     

Transcriptome Analysis Reveals Candidate Genes Involved in Anthocyanin Biosynthesis in Flowers of the Pagoda Tree (Sophora japonica L.)

Journal of Plant Growth Regulation - The flowers of pagoda tree (Sophora japonica L.) are white, which limited its ornamental value and caused few researches on its flower color and anthocyanin...     

Comparative analysis of the gut microbiota composition between two sea snakes,Hydrophis curtus,and Hydrophis cyanocinctus

Coral Reefs - Gut microbiota plays an important role in host nutrition, metabolism, immune, and homeostasis. Although there has been extensive research on gut microbiota over the past decade, few...     

APP Regulates NGF Receptor Trafficking and NGF-Mediated Neuronal Differentiation and Survival

β-amyloid precursor protein (APP) is a key factor in Alzheimer''s disease (AD) but its physiological function is largely undetermined. APP has been found to regulate retrograde transport of nerve growth factor (NGF), which plays a crucial role in mediating neuronal survival and differentiation. Herein, we reveal the mechanism underlying APP-mediated NGF trafficking, by demonstrating a direct interaction between APP and the two NGF receptors, TrkA and p75NTR. Downregulation of APP leads to reduced cell surface levels of TrkA/p75NTR and increased endocytosis of TrkA/p75NTR and NGF. In addition, APP-deficient cells manifest defects in neurite outgrowth and are more susceptible to Aβ-induced neuronal death at physiological levels of NGF. However, APP-deficient cells show better responses to NGF-stimulated differentiation and survival than control cells. This may be attributed to increased receptor endocytosis and enhanced activation of Akt and MAPK upon NGF stimulation in APP-deficient cells. Together, our results suggest that APP mediates endocytosis of NGF receptors through direct interaction, thereby regulating endocytosis of NGF and NGF-induced downstream signaling pathways for neuronal survival and differentiation.     

Liver-specific inactivation of the abetalipoproteinemia gene completely abrogates very low density lipoprotein/low density lipoprotein production in a viable conditional knockout mouse

Conventional knockout of the microsomal triglyceride transfer protein large subunit (lMTP) gene is embryonic lethal in the homozygous state in mice. We have produced a conditional lMTP knockout mouse by inserting loxP sequences flanking exons 5 and 6 by gene targeting. Homozygous floxed mice were born live with normal plasma lipids. Intravenous injection of an adenovirus harboring Cre recombinase (AdCre1) produced deletion of exons 5 and 6 and disappearance of lMTP mRNA and immunoreactive protein in a liver-specific manner. There was also disappearance of plasma apolipoprotein (apo) B-100 and marked reduction in apoB-48 levels. Wild-type mice showed no response, and heterozygous mice, an intermediate response, to AdCre1. Wild-type mice doubled their plasma cholesterol level following a high cholesterol diet. This hypercholesterolemia was abolished in AdCre1-treated lMTP-/- mice, the result of a complete absence of very low/intermediate/low density lipoproteins and a slight reduction in high density lipoprotein. Heterozygous mice showed an intermediate lipoprotein phenotype. The rate of accumulation of plasma triglyceride following Triton WR1339 treatment in lMTP-/- mice was <10% that in wild-type animals, indicating a failure of triglyceride-rich lipoprotein production. Pulse-chase experiments using hepatocytes isolated from wild-type and lMTP-/- mice revealed a failure of apoB secretion in lMTP-/- animals. Therefore, the liver-specific inactivation of the lMTP gene completely abrogates apoB-100 and very low/intermediate/low density lipoprotein production. These conditional knockout mice are a useful in vivo model for studying the role of MTP in apoB biosynthesis and the biogenesis of apoB-containing lipoproteins.     

Fe binding properties of two soybean (Glycine max L.) LEA4 proteins associated with antioxidant activity

Late embryogenesis abundant (LEA) group 4 (LEA4) proteins play an important role in the water stress tolerance of plants. Although they have been hypothesized to stabilize macromolecules in stressed cells, the protective functions and mechanisms of LEA4 proteins are still not clear. In this study, the metal binding properties of two related soybean LEA4 proteins, GmPM1 and GmPM9, were tested using immobilized metal ion affinity chromatography (IMAC). The metal ions Fe(3+), Ni(2+), Cu(2+) and Zn(2+) were observed to bind these two proteins, while Ca(2+), Mg(2+) or Mn(2+) did not. Results from isothermal titration calorimetry (ITC) indicated that the binding affinity of GmPM1 for Fe(3+) was stronger than that of GmPM9. Hydroxyl radicals generated by the Fe(3+)/H(2)O(2) system were scavenged by both GmPM1 and GmPM9 in the absence or the presence of high ionic conditions (100 mM NaCl), although the scavenging activity of GmPM1 was significantly greater than that of GmPM9. These results suggest that GmPM1 and GmPM9 are metal-binding proteins which may function in reducing oxidative damage induced by abiotic stress in plants.