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1.
Lingjun Zhu Mulong Du Dongying Gu Lan Ma Haiyan Chu Na Tong Jinfei Chen Zhengdong Zhang Meilin Wang 《PloS one》2013,8(3)
Background
A recent genome-wide association study has identified a new genetic variant rs7758229 in SLC22A3 for colorectal cancer susceptibility in a Japanese population, but it is unknown whether this newly identified variant is associated with colorectal cancer in other populations, including the Chinese population.Methods
We examined the associations between rs7758229 and colorectal cancer risk among 1,147 cases and 1,203 controls matched by age and sex. Logistic regression model was used to assess the associations.Results
No significant association was found between rs7758229 and colorectal cancer risk (OR = 0.95, 95%CI = 0.84–1.09, P = 0.463). Similar results were observed in the stratification of tumor location (OR = 0.94, 95%CI = 0.80–1.11, P = 0.481 for colon cancer, and OR = 0.96, 95%CI = 0.82–1.13, P = 0.621 for rectum cancer).Conclusions
Our findings did not support an association between rs7758229 in 6q26-q27 and the risk of colorectal cancer in a Chinese population. 相似文献2.
Yan-yan Li Zhi-jian Yang Chuan-wei Zhou Xiang-ming Wang Yun Qian Jian Xu Bei Wang Jun Wu 《PloS one》2013,8(4)
Background
Although adiponectin −11377CG gene polymorphism is implied to be associated with increased type 2 diabetes mellitus (T2DM) risk, results of individual studies are inconsistent.Objective and Methods
A meta-analysis consisting of 12 individual studies, including a total of 6425 participants, was carried out in order to investigate the association of adiponectin −11377CG gene polymorphism with T2DM. The pooled odds ratio (OR) and its corresponding confidence interval (CI) at 95% were assessed through the random- or fixed- effect model.Results
A significant relationship was observed between adiponectin −11377CG gene polymorphism and T2DM under allelic (OR: 1.150, 95% CI: 1.060 to 1.250, P = 0.001), recessive (OR: 1.450, 95% CI: 1.180–1.770, P = 0.0004), dominant (OR: 1.071, 95% CI: 1.013–1.131, P = 0.015), additive (OR: 1.280, 95% CI: 1.090–1.510, P = 0.002), and homozygous genetic models (OR: 1.620, 95% CI: 1.310–1.990, P<0.00001). No significant association was found between them under the heterozygous genetic model (OR: 1.640, 95% CI: 0.850–3.170, P = 0.140).Conclusions
Adiponectin −11377CG gene polymorphism was significantly associated with T2DM risk susceptibility. G allele carriers are predisposed to T2DM risk. 相似文献3.
Hong-Qi Fan Wei Tang Zhi-Xiao Wang Su-Juan Wang Yue-Hua Qin Qi Fu Yuan Gao Min Sun Mei Zhang Hong-Wen Zhou Tao Yang 《PloS one》2013,8(7)
Objective
To examine whether serum uric acid (SUA) is associated with 2-hour postload glucose (2-h PG) in Chinese with impaired fasting plasma glucose (IFG) and/or HbA1c (IA1C).Research Design and Methods
Anthropometric and biochemical examinations, such as SUA concentration, were performed in 3763 individuals from all the villages in Baqiao County, China. A 75-g oral glucose tolerance test (OGTT) was conducted in 1197 Chinese with prediabetes as having IFG (110≤ fasting plasma glucose [FPG] <126 mg/dl and HbA1c <6.5%), IA1C (5.7% ≤ HbA1c <6.5% and FPG <126 mg/dl), or both.Results
The present study included 1197 participants with IFG and/or IA1C (mean age 56.5±10.3 years; 50.6% men). In multivariate linear regression, after adjustment for gender, age, smoking and drinking, body mass index (BMI), systolic and diastolic blood pressure (SBP, DBP), lipid profiles, logarithmic transformed C-reactive protein (log-CRP), estimated glomerular filtration rate (e-GFR), FPG and HbA1c, with a 1-mg/dl increment of SUA, 2-h PG increased by 5.04±0.72 (P<0.001), 3.06±1.08 (P = 0.001), 5.40±1.26 (P<0.001), and 2.34±2.16 mg/dl (P = 0.056) in all participants, in participants with normal glucose tolerance (NGT), with impaired glucose tolerance (IGT), and with 2-h newly diagnosed diabetes (2-h NDM, with 2-h PG ≥200 mg/dl), respectively. In both men and women, 2-h PG increased progressively and significantly from the lower to the upper SUA tertiles (P<0.001). Moreover, in multivariate logistic regression, 1-standard deviation (SD; 1.53 mg/dl) increment of SUA was significantly associated with a 36% higher risk for 2-h NDM (Odds ratio [CI 95%]: 1.36 [1.09–1.99]; P = 0.03).Conclusions
SUA is significantly associated with 2-h PG in Chinese with IFG and/or IA1C. 相似文献4.
Background
Aldosterone synthase (CYP11B2) T-344C gene polymorphism was found to be correlated with atrial fibrillation (AF) risk. However, the results of individual studies remain conflicting.Objective and methods
A meta-analysis including 2,758 subjects from six individual studies was performed to explore the correlation between CYP11B2 T-344C gene polymorphisms and AF. The pooled odds ratios (ORs) and their corresponding 95% confidence intervals (95% CIs) were evaluated by the fixed– or random–effects model.Results
A significant relationship between CYP11B2 T-344C gene polymorphism and AF was found under allelic (OR: 1.26, 95% CI: 1.11–1.42, P = 0.0002), recessive (OR: 1.99, 95% CI: 1.26–3.14, P = 0.003), dominant (OR: 0.903, 95% CI: 0.820–0.994, P = 0.036), homozygous (OR: 1.356, 95% CI: 1.130–1.628, P = 0.001), and additive (OR: 1.153, 95% CI: 1.070–1.243, P = 1.0×10−10) genetic models. No significant association between CYP11B2 T-344C gene polymorphism and AF was found under the heterozygous genetic model (OR: 1.040, 95% CI: 0.956–1.131, P = 0.361).Conclusions
A significant association was found between CYP11B2 T-344C gene polymorphism and AF risk. Individuals with the C allele of CYP11B2 T-344C gene polymorphism have higher risk for AF. 相似文献5.
Ole De Backer Samer Arnous Jacob L?nborg Matthew Brooks Luigi Biasco Anders J?nsson Olaf W. Franzen Lars S?ndergaard 《PloS one》2014,9(12)
Introduction
Preoperative anemia is common in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation (TAVI) and has been linked to a poorer outcome – including a higher 1-year mortality. The aim of this study was to investigate the impact of successful TAVI on baseline anemia.Methods
A total of 253 patients who survived at least 1 year following TAVI were included in this study. The prevalence, predictors and clinical outcome of hemoglobin (Hb)-recovery were assessed.Results
The prevalence of baseline anemia was 49% (n = 124) – recovery from anemia occurred in 40% of the anemic patients (n = 49) at 1 year after TAVI with an increase in mean Hb-level of 1.35 g/dL from baseline. This increase was not related to an improvement in renal function. At multivariate analysis, a high peak gradient (OR 4.82, P = 0.003) was shown to be an independent predictor for Hb-recovery, while blood transfusion (OR 0.31, P = 0.038) and chronic kidney disease (CKD, OR 0.33, P = 0.043) were identified as negative predictors at, respectively, one and two years after TAVI. When compared to patients without baseline anemia, those anemic patients with Hb-recovery had a similar functional improvement (OR 0.98, P = 0.975), whereas those without Hb-recovery had a significantly lower likelihood of functional improvement with ≧2 NYHA classes (OR 0.49, P = 0.034) and a higher likelihood of re-hospitalization within the first year after TAVI (OR 1.91, P = 0.024).Conclusion
Recovery from anemia occurs in 40% of anemic patients at 1 year after TAVI – mainly in those with a high gradient and without CKD. Blood transfusion was found to have a transient adverse effect on this Hb-recovery. Finally, anemic patients without Hb-recovery experience less functional improvement and have a higher re-hospitalization rate within the first year after TAVI. 相似文献6.
Purpose
To examine characteristics of ocular hypertensive subjects and potential associations with estimated cerebrospinal fluid pressure (estCSFP).Methods
The population-based Beijing Eye Study 2011 included 3468 individuals with a mean age of 64.6±9.8 years. Ocular hypertension was defined as intraocular pressure (IOP) >21 mmHg, normal optic nerve head appearance and normal retinal nerve fiber layer thickness. IOP was corrected for its dependence on central corneal thickness (CCT) and corneal curvature radius. Estimated CSFP was calculated as CSFP [mmHg] = 0.44×Body Mass Index [kg/m2]+0.16×Diastolic Blood Pressure [mmHg]−0.18×Age [Years]−1.91. Estimated trans-lamina cribrosa pressure difference (estTLCPD) was IOP–estCSFP.Results
EstCSFP (10.5±3.6 mmHg versus 9.0±3.7 mmHg; P = 0.003) and estTLCPD (12.0±4.4 mmHg versus 5.4±3.8 mmHg; P<0.001) were higher in the ocular hypertensive group than in the normotensive group. In binary regression analysis, ocular hypertension was associated with increased estCSFP (P = 0.03; odds ratio (OR): 1.08; 95% confidence interval (CI): 1.01, 1.17) after adjusting for prevalence of arterial hypertension (P = 0.07; OR: 1.79; 95%CI: 0.96, 3.34), retinal nerve fiber layer thickness (P = 0.03; OR: 0.97; 95%CI: 0.95, 0.997) and blood glucose concentration (P = 0.006; OR: 1.17; 95%CI: 1.04, 1.30).Conclusions
Ocular hypertensive subjects (with IOP correction for CCT and corneal curvature) as compared to ocular normotensive subjects had a significantly higher estCSFP in univariate analysis and in multivariate analysis. Despite of a higher estCSFP, estTLCPD was still markedly higher in ocular hypertensive eyes than in ocular normotensive eyes. 相似文献7.
Martin Friedrichsen Pernille Poulsen J?rgen Wojtaszewski Peter Riis Hansen Allan Vaag Henrik Berg Rasmussen 《PloS one》2013,8(2)
Context and Aims
Carboxylesterase 1 (CES1) appears to play an important role in the control of the metabolism of triglycerides and cholesterol in adipocytes and other cell types including hepatocytes. Therefore, it is relevant to gain insights into the genetic versus non-genetic mechanisms involved in the control of CES1 mRNA expression. Here, we investigated CES1 mRNA expression level in adipose tissue and its association with measures of adiposity and metabolic function in a population of elderly twins. Furthermore, the heritability of CES1 mRNA expression level in adipose tissue and the effect of CES1 gene duplication were assessed.Methodology
A total of 295 monozygotic and dizygotic twin subjects (62–83 years) with (n = 48) or without (n = 247) type 2 diabetes mellitus were enrolled in the study. They were subjected to a standard oral glucose tolerance test and excision of abdominal subcutaneous fat biopsies during the fasting state. Levels of CES1 mRNA and copy number of the gene were assessed by quantitative PCR.Results
CES1 mRNA expression level in adipose tissue was positively associated with body-mass index (P<0.001), homeostasis model assessment-insulin resistance (P = 0.003) and level of fasting glucose (P = 0.002), insulin (P = 0.006), and triglycerides (P = 0.003). The heritability for the expression of CES1 mRNA in adipose tissue was high. CES1 gene duplication was positively associated with insulin sensitivity (P = 0.05) as well as glucose tolerance (P = 0.03) and negatively associated with homeostasis model assessment-insulin resistance (P = 0.02). Duplication of CES1 was not linked to mRNA level of this gene (P = 0.63).Conclusion
CES1 mRNA in adipose tissue appears to be under strong genetic control and was associated with measures of metabolic function raising the possibility of a potential role of this enzyme in the development of type 2 diabetes mellitus. Further studies are needed to understand the potential effect of CES1 gene duplication on adipocyte and whole-body metabolic functions. 相似文献8.
Background
The benefit of corticosteroids in community-acquired pneumonia (CAP) remains controversial. We did a meta-analysis to include all the randomized controlled trials (RCTs) which used corticosteroids as adjunctive therapy, to examine the benefits and risks of corticosteroids in the treatment of CAP in adults.Methods
Databases including Pubmed, EMBASE, the Cochrane controlled trials register, and Google Scholar were searched to find relevant trials. Randomized and quasi-randomized trials of corticosteroids treatment in adult patients with CAP were included. Effects on primary outcome (mortality) and secondary outcomes (adverse events) were accessed in this meta-analysis.Results
Nine trials involving 1001 patients were included. Use of corticosteroids did not significantly reduce mortality (Peto odds ratio [OR] 0.62, 95% confidence interval [CI] 0.37–1.04; P = 0.07). In the subgroup analysis by the severity, a survival benefit was found among severe CAP patients (Peto OR 0.26, 95% CI 0.11–0.64; P = 0.003). In subgroup analysis by duration of corticosteroids treatment, significant reduced mortality was found among patients with prolonged corticosteroids treatment (Peto OR 0.51, 95% CI 0.26–0.97; P = 0.04; I 2 = 37%). Corticosteroids increased the risk of hyperglycemia (Peto OR 2.64, 95% CI 1.68–4.15; P<0.0001), but without increasing the risk of gastroduodenal bleeding (Peto OR 1.67, 95% CI 0.41–6.80; P = 0.47) and superinfection (Peto OR 1.36, 95% CI 0.65–2.84; P = 0.41).Conclusion
Results from this meta-analysis did not suggest a benefit for corticosteroids treatment in patients with CAP. However, the use of corticosteroids was associated with improved mortality in severe CAP. In addition, prolonged corticosteroids therapy suggested a beneficial effect on mortality. These results should be confirmed by future adequately powered randomized trials. 相似文献9.
Camilla Stephens Miguel-ángel López-Nevot Francisco Ruiz-Cabello Eugenia Ulzurrun Germán Soriano Manuel Romero-Gómez Antonia Moreno-Casares M. Isabel Lucena Raúl J. Andrade 《PloS one》2013,8(7)
Background and Aim
The genotype-phenotype interaction in drug-induced liver injury (DILI) is a subject of growing interest. Previous studies have linked amoxicillin-clavulanate (AC) hepatotoxicity susceptibility to specific HLA alleles. In this study we aimed to examine potential associations between HLA class I and II alleles and AC DILI with regards to phenotypic characteristics, severity and time to onset in Spanish AC hepatotoxicity cases.Methods
High resolution genotyping of HLA loci A, B, C, DRB1 and DQB1 was performed in 75 AC DILI cases and 885 controls.Results
The distributions of class I alleles A*3002 (P/Pc = 2.6E-6/5E-5, OR 6.7) and B*1801 (P/Pc = 0.008/0.22, OR 2.9) were more frequently found in hepatocellular injury cases compared to controls. In addition, the presence of the class II allele combination DRB1*1501-DQB1*0602 (P/Pc = 5.1E-4/0.014, OR 3.0) was significantly increased in cholestatic/mixed cases. The A*3002 and/or B*1801 carriers were found to be younger (54 vs 65 years, P = 0.019) and were more frequently hospitalized than the DRB1*1501-DQB1*0602 carriers. No additional alleles outside those associated with liver injury patterns were found to affect potential severity as measured by Hy’s Law criteria. The phenotype frequencies of B*1801 (P/Pc = 0.015/0.42, OR 5.2) and DRB1*0301-DQB1*0201 (P/Pc = 0.0026/0.07, OR 15) were increased in AC DILI cases with delayed onset compared to those corresponding to patients without delayed onset, while the opposite applied to DRB1*1302-DQB1*0604 (P/Pc = 0.005/0.13, OR 0.07).Conclusions
HLA class I and II alleles influence the AC DILI signature with regards to phenotypic expression, latency presentation and severity in Spanish patients. 相似文献10.
Izabela Chojnicka Krzysztof Gajos Katarzyna Strawa Gra?yna Broda Sylwia Fudalej Marcin Fudalej Piotr Stawiński Aleksandra Pawlak Pawe? Krajewski Marcin Wojnar Rafa? P?oski 《PloS one》2013,8(2)
Background
rs6943555 in AUTS2 has been shown to modulate ethanol consumption. We hypothesized that rs6943555 might be associated with completed suicide.Methods
We genotyped rs6943555 in 625 completed suicides and 3861 controls using real-time TaqMan Allelic Discrimination Assay. All individuals were Polish Caucasians.Results
We detected an association between suicide and rs6943555 A allele (OR = 1.17, P = 0.018 for allelic comparison, OR = 1.24, P = 0.013 for dominant, and OR = 1.18, P = 0.020 for co-dominant model of inheritance). The association remained significant after adjusting for age and gender (co-dominant: P = 0.002 and dominant model: P = 0.001). After stratifying suicides according to blood ethanol concentration (BAC≤ 20 mg/dl and BAC > 20 mg/dl) the association remained significant only for cases who committed suicide under influence of alcohol (co-dominant: OR = 1.37, P = 0.004 and dominant model: OR = 1.45, P = 0.006). To validate this finding we genotyped another cohort of 132 cases. We reproduced the association between rs6943555 A allele and suicide under influence of ethanol (allelic comparison: OR = 1.55, P = 0.023; co-dominant : OR = 1.54, P = 0.031; dominant model: OR = 1.84, P = 0.015). Analyzing pooled suicides with BAC >20 mg/dl (N = 300) we found the association of rs6943555 A allele not only vs. controls (allelic OR = 1.41, P = 0.00029) but also vs. cases with BAC ≤ 20 mg/dl (N = 449, allelic OR = 1.33, P = 0.019).Conclusions
In our study rs6943555 A allele is associated with suicide committed after drinking ethanol shortly before death. The rs6943555 A allele may be linked to adverse emotional reaction to ethanol, which could explain the association with lower consumption in general population as well as the predisposition to suicide under influence of ethanol. 相似文献11.
James Whitehorn Tran Nguyen Bich Chau Nguyen Minh Nguyet Duong Thi Hue Kien Nguyen Than Ha Quyen Dinh The Trung Junxiong Pang Bridget Wills Nguyen Van Vinh Chau Jeremy Farrar Martin L. Hibberd Chiea Chuen Khor Cameron P. Simmons 《PloS one》2013,8(3)
Background
A recent genome-wide association study (GWAS) identified susceptibility loci for dengue shock syndrome (DSS) at MICB rs3132468 and PLCE1 rs3740360. The aim of this study was to define the extent to which MICB (rs3132468) and PLCE1 (rs3740360) were associated with less severe clinical phenotypes of pediatric and adult dengue.Methods
3961 laboratory-confirmed dengue cases and 5968 controls were genotyped at MICB rs3132468 and PLCE1 rs3740360. Per-allele odds ratios (OR) with 95% confidence intervals (CI) were calculated for each patient cohort. Pooled analyses were performed for adults and paediatrics respectively using a fixed effects model.Results
Pooled analysis of the paediatric and adult cohorts indicated a significant association between MICB rs3132468 and dengue cases without shock (OR = 1.15; 95%CI: 1.07 – 1.24; P = 0.0012). Similarly, pooled analysis of pediatric and adult cohorts indicated a significant association between dengue cases without shock and PLCE1 rs3740360 (OR = 0.92; 95%CI: 0.85 – 0.99; P = 0.018). We also note significant association between both SNPs (OR = 1.48; P = 0.0075 for MICB rs3132468 and OR = 0.75, P = 0.041 for PLCE1 rs3740360) and dengue in infants.Discussion
This study confirms that the MICB rs3132468 and PLCE1 rs3740360 risk genotypes are not only associated with DSS, but are also associated with less severe clinical phenotypes of dengue, as well as with dengue in infants. These findings have implications for our understanding of dengue pathogenesis. 相似文献12.
Chenxi Wu Wuying Cheng Yi Sun Yonghong Dang Fengying Gong Huijuan Zhu Naishi Li Fang Li Zhaohui Zhu 《PloS one》2014,9(12)
Purpose
This study aims at using 18F-FDG microPET to monitor the brown adipose tissue (BAT) glucose metabolism in obese and diabetic mouse models under different interventions, and study the therapeutic potential of BAT activation for weight loss and lowering of blood glucose in these models.Methods
Obese mice were established by a high-fat diet for eight weeks, and diabetes mellitus(DM) models were induced with Streptozocin in obese mice. 18F-FDG microPET was used to monitor BAT function during obese and DM modeling, and also after BRL37344 (a β3-adrenergic receptor agonist) or levothyroxine treatment. The BAT function was correlated with the body weight and blood glucose levels.Results
Compared with the controls, the obese mice and DM mice showed successively lower 18F-FDG uptake in the interscapular BAT (P = 0.036 and <0.001, respectively). After two-week BRL37344 treatment, the BAT uptake was significantly elevated in both obese mice (P = 0.010) and DM mice (P = 0.004), accompanied with significantly decreased blood glucose levels (P = 0.023 and 0.036, respectively). The BAT uptake was negatively correlated with the blood glucose levels in both obese mice (r = −0.71, P = 0.003) and DM mice (r = −0.74, P = 0.010). BRL37344 treatment also caused significant weight loss in the obese mice (P = 0.001). Levothyroxine treatment increased the BAT uptake in the control mice (P = 0.025) and obese mice (P = 0.013), but not in the DM mice (P = 0.45).Conclusion
The inhibited BAT function in obese and DM mice can be re-activated by β3-adrenergic receptor agonist or thyroid hormone, and effective BAT activation may lead to weight loss and blood glucose lowering. Activating BAT can provide a new treatment strategy for obesity and DM. 相似文献13.
Background
Hypoxia-inducible factor-1α (HIF-1α) and heme oxygenase-1(HO-1) are involved in the tissue hypoxic response.Hypothesis
HIF-1α and HO-1 levels may predict cardiac ischemia and adverse cardiac events during non-cardiac surgery.Methods
HIF-1α and HO-1 levels were determined in elderly patients undergoing non-cardiac surgery preoperatively and at 30 minutes, 48 and 72 hours postoperatively. Results were analyzed with respect to the occurrence of adverse cardiac events.Results
A total of 380 patients with a mean age of 65.3 years were included, and 54 (14.2%) who had adverse cardiac events during or after the surgery. HIF-1α and HO-1 levels in the adverse cardiac event group were significantly higher than in the group without adverse cardiac events at each time point (all, P<0.05). In multivariates regression analysis, the odds of an adverse cardiac event was increased by every 1-year increase in age (odd ratio [OR] 1.39, P<0.001), abnormal ECG at baseline (OR 2.27, P = 0.048), myocardial infarction history (OR 3.18, P = 0.015), and positive baseline cTnI level were associated with an increased likelihood of an adverse cardiac event (OR 8.78, P = 0.019), and for every 1 unit increase of HO-1, the odds of an adverse cardiac event increased by 1.30 (P = 0.002).Conclusion
Determination of preoperative HO-1 levels may aid in identifying patients at risk of developing ischemic cardiac events. 相似文献14.
Background
Most liver transplant recipients receive calcineurin inhibitors (CNIs), especially tacrolimus and cyclosporine, as immunosuppressant agents to prevent rejection. A controversy exists as to whether the outcomes of hepatitis C virus (HCV)-infected liver transplant patients differ based on the CNIs used. This meta-analysis compares the clinical outcomes of tacrolimus-based and cyclosporine-based immunosuppression, especially cases of HCV recurrence in liver transplant patients with end-stage liver disease caused by HCV infection.Methods
Related articles were identified from the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, Medline, and Embase. Meta-analyses were performed for the results of homogeneous studies.Results
Nine randomized or quasi-randomized controlled trials were included. The total effect size of mortality (RR = 0.98, 95% CI: 0.77–1.25, P = 0.87) and graft loss (RR = 1.05, 95% CI: 0.83–1.33, P = 0.67) showed no significant difference between the two groups irrespective of duration of immunosuppressant therapy after liver transplantation. In addition, the HCV recurrence-induced mortality (RR = 1.11, 95% CI: 0.66–1.89, P = 0.69), graft loss (RR = 1.62, 95% CI: 0.64–4.07, P = 0.31) and retransplantation (RR = 1.40, 95% CI: 0.48–4.09, P = 0.54), as well as available biopsies, confirmed that histological HCV recurrences (RR = 0.92, 95% CI: 0.71–1.19, P = 0.51) were similar.Conclusion
These results suggested no difference in posttransplant HCV recurrence-induced mortality, graft loss and retransplantation, as well as histological HCV recurrence in patients treated with tacrolimus-based and cyclosporine-based immunosuppresion. 相似文献15.
Caren E. Smith Katherine L. Tucker Tammy M. Scott Maria Van Rompay Josiemer Mattei Chao-Qiang Lai Laurence D. Parnell Mireia Junyent Yu-Chi Lee Bibiana Garcia-Bailo José M. Ordovás 《PloS one》2009,4(5)
Background
Apolipoprotein C3 (APOC3) modulates triglyceride metabolism through inhibition of lipoprotein lipase, but is itself regulated by insulin, so that APOC3 represents a potential mechanism by which glucose metabolism may affect lipid metabolism. Unfavorable lipoprotein profiles and impaired glucose metabolism are linked to cognitive decline, and all three conditions may decrease lifespan. Associations between apolipoprotein C3 (APOC3) gene polymorphisms and impaired lipid and glucose metabolism are well-established, but potential connections between APOC3 polymorphisms, cognitive decline and diabetes deserve further attention.Methods
We examined whether APOC3 single nucleotide polymorphisms (SNPs) m482 (rs2854117) and 3u386 (rs5128) were related to cognitive measures, whether the associations between cognitive differences and genotype were related to metabolic differences, and how diabetes status affected these associations. Study subjects were Hispanics of Caribbean origin (n = 991, aged 45–74) living in the Boston metropolitan area.Results
Cognitive and metabolic measures differed substantially by type II diabetes status. In multivariate regression models, APOC3 m482 AA subjects with diabetes exhibited lower executive function (P = 0.009), Stroop color naming score (P = 0.014) and Stroop color-word score (P = 0.022) compared to AG/GG subjects. APOC3 m482 AA subjects with diabetes exhibited significantly higher glucose (P = 0.032) and total cholesterol (P = 0.028) compared to AG/GG subjects. APOC3 3u386 GC/GG subjects with diabetes exhibited significantly higher triglyceride (P = 0.004), total cholesterol (P = 0.003) and glucose (P = 0.016) compared to CC subjects.Conclusions
In summary, we identified significant associations between APOC3 polymorphisms, impaired cognition and metabolic dysregulation in Caribbean Hispanics with diabetes. Further research investigating these relationships in other populations is warranted. 相似文献16.
Jie Wen Tina R?nn Anders Olsson Zhen Yang Bin Lu Yieping Du Leif Groop Charlotte Ling Renming Hu 《PloS one》2010,5(2)
Background
Recent genome-wide association studies (GWASs) have reported several genetic variants to be reproducibly associated with type 2 diabetes. Additional variants have also been detected from a metaanalysis of three GWASs, performed in populations of European ancestry. In the present study, we evaluated the influence of 17 genetic variants from 15 candidate loci, identified in type 2 diabetes GWASs and the metaanalysis, in a Han Chinese cohort.Methodology/Principal Findings
Selected type 2 diabetes–associated genetic variants were genotyped in 1,165 type 2 diabetic patients and 1,136 normoglycemic control individuals of Southern Han Chinese ancestry. The OR for risk of developing type 2 diabetes was calculated using a logistic regression model adjusted for age, sex, and BMI. Genotype-phenotype associations were tested using a multivariate linear regression model. Genetic variants in CDKN2A/B, CDKAL1, TCF7L2, TCF2, MC4R, and PPARG showed a nominal association with type 2 diabetes (P≤0.05), of whom the three first would stand correction for multiple testing: CDKN2A/B rs10811661, OR: 1.26 (1.12–1.43) P = 1.8*10−4; CDKAL1 rs10946398, OR: 1.23 (1.09–1.39); P = 7.1*10−4, and TCF7L2 rs7903146, OR: 1.61 (1.19–2.18) P = 2.3 * 10−3. Only nominal phenotype associations were observed, notably for rs8050136 in FTO and fasting plasma glucose (P = 0.002), postprandial plasma glucose (P = 0.002), and fasting C-peptide levels (P = 0.006) in the diabetic patients, and with BMI in controls (P = 0.033).Conclusions/Significance
We have identified significant association between variants in CDKN2A/B, CDKAL1 and TCF7L2, and type 2 diabetes in a Han Chinese cohort, indicating these genes as strong candidates conferring susceptibility to type 2 diabetes across different ethnicities. 相似文献17.
Background
The prognostic significance of circulating tumor cells (CTCs) detected in patients with non-small-cell lung cancer (NSCLC) is still inconsistent. We aimed to assess the prognostic relevance of CTCs using a meta-analysis.Methods
We searched PubMed, Web of Science and EMBASE for relevant studies that assessed the prognostic relevance of CTCs in NSCLC. Statistical analyses were conducted to calculate the summary incidence, odds ratio, relative risks (RRs) and 95% confidence intervals (CIs) using fixed or random-effects models according to the heterogeneity of included studies.Results
A total of 20 studies, comprising 1576 patients, met the inclusion criteria. In identified studies, CTCs were not correlated with histology (adenocarcinoma vs squamous cell carcinoma) (odds ratio [OR] = 0.88; 95% confidence interval [CI]: 0.59–1.33; Z = –0.61; P = 0.545). However, pooled analyses showed that CTCs were associated with lymph node metastasis (OR = 2.06; 95% CI: 1.18–3.62; Z = 2.20; P = 0.027) and tumor stage (OR = 1.95; 95% CI: 1.08–3.54; Z = 2.53; P = 0.011). Moreover, CTCs were significantly associated with shorter overall survival (relative risk [RR] = 2.19; 95% CI: 1.53–3.12; Z = 4.32; P<0.0001) and progression-free/disease-free survival (RR = 2.14; 95% CI: 1.36–3.38; Z = 3.28; P<0.0001).Conclusion
The presence of CTCs indicates a poor prognosis in patients with NSCLC. Further well-designed prospective studies are required to explore the clinical applications of CTCs in lung cancer. 相似文献18.
Background
DHA is accumulated in the central nervous system (CNS) before birth and is involved in early developmental processes, such as neurite outgrowth and gene expression.Objective
To determine whether fetal DHA insufficiency occurs and constrains CNS development in term gestation infants.Design
A risk reduction model using a randomized prospective study of term gestation single birth healthy infants born to women (n = 270) given a placebo or 400 mg/day DHA from 16 wk gestation to delivery. Fetal DHA deficiency sufficient to constrain CNS development was assessed based on increased risk that infants in the placebo group would not achieve neurodevelopment scores in the top quartile of all infants in the study.Results
Infants in the placebo group were at increased risk of lower language development assessed as words understood (OR 3.22, CL 1.49–6.94, P = 0.002) and produced (OR 2.61, CL 1.22–5.58, P = 0.01) at 14 mo, and words understood (OR 2.77, CL 1.23–6.28, P = 0.03) and sentences produced (OR 2.60, CL 1.15–5.89, P = 0.02) at 18 mo using the McArthur Communicative Developmental Inventory; receptive (OR 2.23, CL 1.08–4.60, P = 0.02) and expressive language (OR 1.89, CL 0.94–3.83, P = 0.05) at 18 mo using the Bayley Scales of Infant Development III; and visual acuity (OR 2.69, CL 1.10–6.54, P = 0.03) at 2 mo.Trial Registration
ClinicalTrials.gov NCT00620672 相似文献19.
Lei Shao Liang Xu Qi Sheng You Ya Xing Wang Chang Xi Chen Hua Yang Jin Qiong Zhou Jost B. Jonas Wen Bin Wei 《PloS one》2013,8(3)
Purpose
To determine prevalence and associations of incomplete posterior vitreous detachment (PVD).Methods
The population-based cross-sectional Beijing Eye Study 2011 included 3468 individuals with a mean age of 64.6±9.8 years (range: 50–93 years). A detailed ophthalmic examination was performed including spectral-domain optical coherence tomography (SD-OCT). Incomplete PVD was differentiated into type 1 (shallow PVD with circular perifoveal vitreous attachment), type 2 (PVD reaching fovea but not foveola), type 3 (shallow PVD with pinpoint vitreous attachment at the foveola), and type 4 (PVD completely detached from the macula, attached to the optic disc).Results
An incomplete PVD was detected in 3948 eyes (prevalence: 60.5±0.6%; 95% Confidence Interval (CI): 59.3%,61.7%) of 2198 subjects (67.1±0.8%;95%CI: 65.6%,68.7%). Type 1 PVD was seen in 3090 (78.3%) eyes, type 2 PVD in 504 (12.8%) eyes, type 3 PVD in 70 (1.8%) eyes, and type 4 PVD in 284 (7.2%) eyes. Prevalence of incomplete PVD was associated with younger age (P<0.001;OR:0.91), male gender (P<0.001;OR:0.64), rural region of habitation (P<0.001;OR:0.49), larger corneal diameter (P = 0.04;OR:0.91), better best corrected visual acuity (P = 0.02;OR:0.41), and hyperopic refractive error (P<0.001;OR:1.15). The type of incomplete PVD was associated with higher age (P<0.001), urban region of habitation (P<0.001), myopic refractive error (P = 0.001), thinner cornea (P = 0.005), and better best corrected visual acuity (P = 0.056).Conclusions
In adult Chinese in Greater Beijing, prevalence of an incomplete PVD (detected in 67.1% subjects) was associated with younger age, male gender, rural region of habitation, larger corneal diameter, better best corrected visual acuity and hyperopic refractive error. 相似文献20.
Yu Lu Zhitong Wu Qiliu Peng Liping Ma Xiaolian Zhang Jiangyang Zhao Xue Qin Shan Li 《PloS one》2014,9(10)