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1.
Background
It is unclear whether the loss of physiological complexity during the aging process is due to genetic variations. The APOE gene has been studied extensively in regard to its relationship with aging-associated medical illness. We hypothesize that diminished physiological complexity, as measured by heart rate variability, is influenced by polymorphisms in the APOE allele among elderly individuals.Methodology/Principal Findings
A total of 102 robust, non-demented, elderly subjects with normal functions of daily activities participated in this study (97 males and 5 females, aged 79.2±4.4 years, range 72–92 years). Among these individuals, the following two APOE genotypes were represented: ε4 non-carriers (n = 87, 85.3%) and ε4 carriers (n = 15, 14.7%). Multi-scale entropy (MSE), an analysis used in quantifying complexity for nonlinear time series, was employed to analyze heart-rate dynamics. Reduced physiological complexity, as measured by MSE, was significantly associated with the presence of the APOE ε4 allele in healthy elderly subjects, as compared to APOE ε4 allele non-carriers (24.6±5.5 versus 28.9±5.2, F = 9.429, p = 0.003, respectively).Conclusions/Significance
This finding suggests a role for the APOE gene in the diminished physiological complexity seen in elderly populations. 相似文献2.
Christopher A. Hostage Kingshuk Roy Choudhury Pudugramam Murali Doraiswamy Jeffrey R. Petrella for the Alzheimer’s Disease Neuroimaging Initiative 《PloS one》2013,8(2)
Objective
To investigate whether there is a specific dose-dependent effect of the Apolipoprotein E (APOE) ε4 and ε2 alleles on hippocampal volume, across the cognitive spectrum, from normal aging to Alzheimer’s Disease (AD).Materials and Methods
We analyzed MR and genetic data on 662 patients from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database–198 cognitively normal controls (CN), 321 mild-cognitive impairment (MCI) subjects, and 143 AD subjects–looking for dose-dependent effects of the ε4 and ε2 alleles on hippocampal volumes. Volumes were measured using a fully-automated algorithm applied to high resolution T1-weighted MR images. Statistical analysis consisted of a multivariate regression with repeated-measures model.Results
There was a dose-dependent effect of the ε4 allele on hippocampal volume in AD (p = 0.04) and MCI (p = 0.02)–in both cases, each allele accounted for loss of >150 mm3 (approximately 4%) of hippocampal volume below the mean volume for AD and MCI subjects with no such alleles (Cohen’s d = −0.16 and −0.19 for AD and MCI, respectively). There was also a dose-dependent, main effect of the ε2 allele (p<0.0001), suggestive of a moderate protective effect on hippocampal volume–an approximately 20% per allele volume increase as compared to CN with no ε2 alleles (Cohen’s d = 0.23).Conclusion
Though no effect of ε4 was seen in CN subjects, our findings confirm and extend prior data on the opposing effects of the APOE ε4 and ε2 alleles on hippocampal morphology across the spectrum of cognitive aging. 相似文献3.
Yan-Wei Yin Qian-Qian Sun Bei-Bei Zhang Ai-Min Hu Hong-Li Liu Qi Wang Zhi-Zhen Hou 《PloS one》2013,8(6)
Background
Epidemiological studies have evaluated the association between apolipoprotein E (ApoE) gene polymorphism and coronary artery disease (CAD) risk which developed inconsistent conclusions. To derive a more precise estimation of the relationship in Chinese population, we performed this meta-analysis.Methods
Databases, including PubMed, EMbase, Web of Science, CBMdisc and CNKI, were searched to get the genetic association studies. Additionally, hand searching of the references of identified articles were performed. All the statistical tests were performed using Review Manager 5.1.2 and Stata 11.0.Results
We identified a total of 40 studies, including 4,564 CAD cases and 3,985 controls. The results showed evidence for significant association between ApoE ε4 allele and CAD risk (for ε2/ε4 vs. ε3/ε3: OR = 1.86, 95% CI = 1.42–2.43, p<0.00001; for ε3/ε4 vs. ε3/ε3: OR = 2.34, 95% CI = 2.07–2.65, p<0.00001; for ε4/ε4 vs. ε3/ε3: OR = 2.89, 95% CI = 1.87–4.47, p<0.00001; for ε4 allele vs. ε3 allele: OR = 2.11, 95% CI = 1.91–2.35, p<0.00001).Conclusions
The present meta-analysis suggests an association between ApoE ε4 allele and increased risk of CAD in Chinese population. However, due to the small sample size in most of the included studies and the selection bias existed in some studies, the results should be interpreted with caution. 相似文献4.
Yuan-Pin Hung Nan-Yao Lee Sheng-Hsiang Lin Ho-Ching Chang Chi-Jung Wu Chia-Ming Chang Po-Lin Chen Hsiao-Ju Lin Yi-Hui Wu Pei-Jane Tsai Yau-Sheng Tsai Wen-Chien Ko 《PloS one》2012,7(11)
Background
PPARγ and RBP4 are known to regulate lipid and glucose metabolism and insulin resistance. The influences of PPARγ (C1431T and Pro12Ala) and RBP4 (−803GA) polymorphisms on metabolic syndrome in HIV-infected patients receiving anti-retroviral therapy were examined in this study.Materials and Methods
A cross-sectional study of HIV-1 infected adults with antiretroviral therapy for more than one year in the National Cheng Kung University Hospital was conducted. The gene polymorphisms were determined by quantitative PCR.Results
Ninety-one patients were included in the study. Eighty-two (90.1%) patients were males with a mean age of 44.4 years. For the C1431T polymorphism in PPARγ, while patients with the T allele (48.4%) had trends toward lower rate of hypertriglyceridemia, the borderline significance together with insignificant power did not support the protective effect of the T allele against development of hypertriglyceridemia. For the Pro12Ala polymorphism in PPARγ, although patients with the Pro/Ala genotype (8.8%) had a higher level of serum LDL (138.0 vs. 111.5 mg/dl, P = 0.04) and trends toward higher rates of hypercholesterolemia and serum LDL>110 mg/dl, these variables were found to be independent of the Pro/Ala genotype in the multivariate analysis. For the −803GA polymorphism in RBP4, patients with the A allele (23.1%) more often had insulin resistance (HOMA>3.8; 33.3 vs. 8.7%, P = 0.01) and more often received anti-hypoglycemic drugs (14.3 vs. 1.4%, P = 0.04). The detrimental effect of the A allele in RBP4 −803GA polymorphism on development of insulin resistance was supported by the multivariate analysis adjusting for covariates.Conclusion
The impacts of PPARγ C1431T and Pro12Ala polymorphisms on metabolism in HIV-infected patients are not significant. RBP4 −803GA polymorphism has increased risk of insulin resistance in HIV-infected patients with anti-retroviral therapy. 相似文献5.
Xuefeng Wang Fengli Jiang Yu Liang Lina Xu Hongbo Li Yali Liu Shiguo Liu Yuanhua Ye 《PloS one》2014,9(9)
Objective
The purpose of our study is to investigate the relationship between IL-1β -31C/T (rs1143627) and -511T/C (rs16944) polymorphisms and the preeclampsia (PE), and analyze the Linkage disequilibrium (LD) and haplotype frequency of the two polymorphism loci.Methods
Polymorphisms at -31C/T and -511T/C of IL-1β were genotyped with the method of polymerase chain reaction-restriction fragment length polymorphism (PCR- RFLP) in 232 PE and 447 control subjects. Genotype and allele frequencies between case-control groups were compared by chi-square(X2) tests. Two-point LD and haplotype frequency analyses were done with the software Haploview4.2.Results
Significant statistical differences were found between PE and control groups regarding genotype and allele frequencies of the two polymorphisms of IL-1β (For IL-1β -31C/T: X2 = 11.478, P = 0.003; For IL-1β-511T/C: X2 = 9.687, P = 0.008). LD analysis revealed that the IL-1β -31C/T SNP was in high LD with the IL-1β-511C/T SNP(D′ = 0.92, r2 = 0.79). Both CT and TC haplotypes showed significant differences between case and control groups. Only the plasma level of Prothrombin Time had a significantly statistical difference among TT, CT and CC groups of the preeclamptic two polymorphisms of IL-1β-31C/T and -511T/C (for IL-1β-31C/T, F = 1.644, P = 0.01; F = 1.587, P = 0.016).Conclusion
Our results revealed IL-1β was associated with the PE in Chinese Han population. The CT haplotype may increase the risk of PE, while haplotype TC could be considered as a protective haplotype of PE. 相似文献6.
Caíque Silveira Martins da Fonseca Adenor Almeida Pimenta Filho Bianka Santana dos Santos César Augusto da Silva Ana Lúcia Coutinho Domingues James Stuart Owen Vera Lúcia de Menezes Lima 《PloS one》2014,9(7)
Background
Schistosomiasis mansoni is a parasitic liver disease, which causes several metabolic disturbances. Here, we evaluate the influence of Apolipoprotein E (APOE) gene polymorphism, a known modulator of lipid metabolism, on plasma lipid levels in patients with hepatosplenic schistosomiasis.Methodology/Principal Findings
Blood samples were used for APOE genotyping and to measure total cholesterol (TC), LDL-C, HDL-C and triglycerides. Schistosomiasis patients had reduced TC, LDL-C and triglycerides (25%, 38% and 32% lower, respectively; P<0.0001) compared to control individuals, whereas HDL-C was increased (10% higher; P = 0.0136). Frequency of the common alleles, ε2, ε3 and ε4, was similar (P = 0.3568) between controls (n = 108) and patients (n = 84), implying that APOE genotype did not affect susceptibility to the advanced stage of schistosomiasis. Nevertheless, while patient TC and LDL-C levels were significantly reduced for each allele (except TC in ε2 patients), changes in HDL-C and triglycerides were noted only for the less common ε2 and ε4 alleles. The most striking finding, however, was that accepted regulation of plasma lipid levels by APOE genotype was disrupted by schistosomiasis. Thus, while ε2 controls had higher TC and LDL-C than ε3 carriers, these parameters were lower in ε2 versus ε3 patients. Similarly, the inverse relationship of TG levels in controls (ε2>ε3>ε4) was absent in patients (ε2 or ε4>ε3), and the increase in HDL-C of ε2 or ε4 patients compared to ε3 patients was not seen in the control groups.Conclusion/Significance
We confirm that human schistosomiasis causes dyslipidemia and report for the first time that certain changes in plasma lipid and lipoprotein levels depend on APOE gene polymorphism. Importantly, we also concluded that S. mansoni disrupts the expected regulation of plasma lipids by the different ApoE isoforms. This finding suggests ways to identify new metabolic pathways affected by schistosomiasis and also potential molecular targets to treat associated morbidities. 相似文献7.
Hoi Kin Wong Kwok Leung Ong Raymond Y. H. Leung Tommy T. Cheung Aimin Xu Tai Hing Lam Karen S. L. Lam Bernard M. Y. Cheung 《PloS one》2013,8(8)
Objective
Adrenomedullin (ADM) and adiponectin are both involved in inflammation and cardiovascular diseases. The plasma levels of these peptides are influenced by single nucleotide polymorphisms (SNPs) in the ADM and ADIPOQ genes respectively. There is some evidence that ADM may regulate adiponectin gene expression, but whether adiponectin can regulate ADM expression is unclear, and was therefore investigated.Methods
Plasma ADM level was measured in 476 subjects in the Hong Kong Cardiovascular Risk Factor Prevalence Study-2 (CRISPS2). We genotyped them for 2 ADIPOQ SNPs that are known to be associated with plasma adiponectin level.Results
The minor allele frequencies of ADIPOQ SNPs rs182052 and rs12495941 were 40.6% and 42.2% respectively. Plasma ADM level was significantly associated with rs182052 after adjusting for age and sex (β = 0.104, P = 0.023) but not with rs12495941 (β = 0.071, P = 0.120). In multivariate analysis, plasma ADM level increased with the number of minor alleles of rs182052 (P = 0.013). Compared to subjects with GG genotype, subjects with AA genotype had 17.7% higher plasma ADM level (95% CI: 3.6%–33.7%). Subgroup analysis revealed that the association was significant in diabetic patients (β = 0.344, P = 0.001) but not in non-diabetic subjects.Conclusion
Plasma ADM level is related to SNP rs182052 in the ADIPOQ gene. Our findings provide new evidence of the interplay between these two important peptides in cardiovascular disease and diabetes. Knowing the genotype may help to refine the interpretation of these biomarkers. 相似文献8.
Introduction
Diagnosis of mild TBI is hampered by the lack of imaging or biochemical measurements for identifying or quantifying mild TBI in a clinical setting. We have previously shown increased biomarker levels of protein reflecting axonal (neurofilament light protein and tau) and glial (GFAP and S-100B) damage in cerebrospinal fluid (CSF) after a boxing bout. The aims of this study were to find other biomarkers of mild TBI, which may help clinicians diagnose and monitor mild TBI, and to calculate the role of APOE ε4 allele genotype which has been associated with poor outcome after TBI.Materials and Methods
Thirty amateur boxers with a minimum of 45 bouts and 25 non-boxing matched controls were included in a prospective cohort study. CSF and blood were collected at one occasion between 1 and 6 days after a bout, and after a rest period for at least 14 days (follow up). The controls were tested once. CSF levels of neurofilament heavy (pNFH), amyloid precursor proteins (sAPPα and sAPPβ), ApoE and ApoA1 were analyzed. In blood, plasma levels of Aβ42 and ApoE genotype were analyzed.Results
CSF levels of pNFH were significantly increased between 1 and 6 days after boxing as compared with controls (p<0.001). The concentrations decreased at follow up but were still significantly increased compared to controls (p = 0.018). CSF pNFH concentrations correlated with NFL (r = 0.57 after bout and 0.64 at follow up, p<0.001). No significant change was found in the other biomarkers, as compared to controls. Boxers carrying the APOE ε4 allele had similar biomarker concentrations as non-carriers.Conclusions
Subconcussive repetitive trauma in amateur boxing causes a mild TBI that may be diagnosed by CSF analysis of pNFH, even without unconsciousness or concussion symptoms. Possession of the APOE ε4 allele was not found to influence biomarker levels after acute TBI. 相似文献9.
Background
Numerous studies have investigated the relationship between apolipoprotein (Apo) E gene polymorphisms and gallbladder stone disease (GSD) across ethnic populations; however, the results are often inconsistent. This meta-analysis aims to comprehensively evaluate the influence of a common ε2/ε3/ε4 polymorphism in Apo E gene on the risk of gallbladder stone disease.Method
Data were analyzed using the RevMan software (V5.1) and a random-effects model was applied irrespective of between-study heterogeneity. Publication bias was weighed using the fail-safe number.Results
There were 17 study populations totaling 1773 cases and 2751 controls for ε2/ε3/ε4 polymorphism of Apo E gene. Overall comparison of alleles ε2 with ε3 in all study populations yielded a 16% decreased risk for GSD (95% confidence interval [95% CI]: 0.68–1.05; P = 0.31; I2 = 13%), and comparison of alleles ε4 with ε3 yielded a 25% increased risk (95% confidence interval [95% CI]: 0.97–1.61; P = 0.0003; I2 = 63%). Subgroup analysis by study design indicated that the magnitude of association in hospital-based studies was largely significantly strengthened for ε4 allelic model (odds ratio [OR] = 1.46; 95% CI: 1.05–2.02; p = 0.0007; I2 = 65%). Subgroup analysis by age of controls indicated a remarkably significant elevation in the magnitude of association in age >50 subgroups in ε4 allelic model (OR = 1.50; 95% CI: 1.03–2.19; p = 0.0009; I2 = 72%). Moreover, subgroup analysis by cases gender indicated a reduction in the magnitude of association in male<30% studies for E2/2 genotypic model (OR = 0.32; 95% CI: 0.07–1.49; p = 0.16; I2 = 45%).Conclusions
Our results reveal that Apo E gene ε4 allele is a risk factor of gallbladder stone disease, especially in elder people and Chinese population. 相似文献10.
Frank Schraml Kewei Chen Napatkamon Ayutyanont Roontiva Auttawut Jessica B. S. Langbaum Wendy Lee Xiaofen Liu Dan Bandy Stephanie Q. Reeder Gene E. Alexander Richard J. Caselli Adam S. Fleisher Eric M. Reiman the Alzheimer’s Disease Neuroimaging Initiative 《PloS one》2013,8(6)
Background
We introduced a hypometabolic convergence index (HCI) to characterize in a single measurement the extent to which a person’s fluorodeoxyglucose positron emission tomogram (FDG PET) corresponds to that in Alzheimer’s disease (AD). Apolipoprotein E ε4 (APOE ε4) gene dose is associated with three levels of risk for late-onset AD. We explored the association between gene dose and HCI in cognitively normal ε4 homozygotes, heterozygotes, and non-carriers.Methods
An algorithm was used to characterize and compare AD-related HCIs in cognitively normal individuals, including 36 ε4 homozygotes, 46 heterozygotes, and 78 non-carriers.Results
These three groups differed significantly in their HCIs (ANOVA, p = 0.004), and there was a significant association between HCIs and gene dose (linear trend, p = 0.001).Conclusions
The HCI is associated with three levels of genetic risk for late-onset AD. This supports the possibility of using a single FDG PET measurement to help in the preclinical detection and tracking of AD. 相似文献11.
N. Maritza Dowling Carey E. Gleason JoAnn E. Manson Howard N. Hodis Virginia M. Miller Eliot A. Brinton Genevieve Neal-Perry M. Nanette Santoro Marcelle Cedars Rogerio Lobo George R. Merriam Whitney Wharton Frederick Naftolin Hugh Taylor S. Mitchell Harman Sanjay Asthana 《PloS one》2013,8(7)
Objectives
While global measures of cardiovascular (CV) risk are used to guide prevention and treatment decisions, these estimates fail to account for the considerable interindividual variability in pre-clinical risk status. This study investigated heterogeneity in CV risk factor profiles and its association with demographic, genetic, and cognitive variables.Methods
A latent profile analysis was applied to data from 727 recently postmenopausal women enrolled in the Kronos Early Estrogen Prevention Study (KEEPS). Women were cognitively healthy, within three years of their last menstrual period, and free of current or past CV disease. Education level, apolipoprotein E ε4 allele (APOE4), ethnicity, and age were modeled as predictors of latent class membership. The association between class membership, characterizing CV risk profiles, and performance on five cognitive factors was examined. A supervised random forest algorithm with a 10-fold cross-validation estimator was used to test accuracy of CV risk classification.Results
The best-fitting model generated two distinct phenotypic classes of CV risk 62% of women were “low-risk” and 38% “high-risk”. Women classified as low-risk outperformed high-risk women on language and mental flexibility tasks (p = 0.008) and a global measure of cognition (p = 0.029). Women with a college degree or above were more likely to be in the low-risk class (OR = 1.595, p = 0.044). Older age and a Hispanic ethnicity increased the probability of being at high-risk (OR = 1.140, p = 0.002; OR = 2.622, p = 0.012; respectively). The prevalence rate of APOE-ε4 was higher in the high-risk class compared with rates in the low-risk class.Conclusion
Among recently menopausal women, significant heterogeneity in CV risk is associated with education level, age, ethnicity, and genetic indicators. The model-based latent classes were also associated with cognitive function. These differences may point to phenotypes for CV disease risk. Evaluating the evolution of phenotypes could in turn clarify preclinical disease, and screening and preventive strategies.ClinicalTrials.gov NCT00154180相似文献12.
13.
Xinyu Li Lin Bai Jing Fang Shengping Hou Qingyun Zhou Hongsong Yu Aize Kijlstra Peizeng Yang 《PloS one》2014,9(5)
Purpose
To investigate the associations of single nucleotide polymorphisms (SNPs) of three genes (IL-12B, IL-12Rβ1 and IL-12Rβ2) in Behcet''s disease (BD) and Vogt-Koyanagi-Harada (VKH) syndrome in a Chinese Han population.Methods
A total of 806 BD cases, 820 VKH patients, and 1600 healthy controls were involved in this study. The first investigation included 400 BD patients, 400 VKH cases, and 600 healthy individuals. A second confirmatory study included a separate set of 406 BD patients, 420 VKH cases and another 1000 normal controls. Genotyping was carried out by PCR-restriction fragment length polymorphism assay and results were validated by using direct sequencing. The χ2 test was performed to compare the allele and genotype frequencies between cases and healthy controls.Results
This study comprised two phases. In the first phase study, a significantly increased frequency of the rs3212227/IL-12B genotype CC and C allele was found in BD patients as compared to controls (Bonferroni corrected p value (pc) = 0.009, OR 1.8; pc = 0.024, OR 1.3, respectively). Moreover, the frequency of the C allele of rs3212227/IL-12B was also significantly increased in VKH patients (pc = 0.012, OR 1.3, 95% CI 1.1 to 1.6). No associations were found for the other seven tested SNPs either in BD or VKH disease. The second study as well as the combined data confirmed the significant association of rs3212227/IL-12B with BD (CC genotype: combined pc = 6.3×10−7, OR = 1.8; C allele: combined pc = 2.0×10−5, OR = 1.3, respectively) and the C allele frequency of rs3212227/IL-12B as the risk factor to VKH patients (combined pc = 2.5×10−5, OR 1.3, 95% CI 1.2 to 1.5).Conclusions
Our study revealed that the IL-12B gene is involved both in the susceptibility to BD as well as VKH syndrome. 相似文献14.
Cuili Wang Robert L. Kane Dongjuan Xu Lingui Li Weihua Guan Hui Li Qingyue Meng 《PloS one》2013,8(12)
Objectives
Prior evidence suggests geographic disparities in the effect of maternal education on child nutritional status between countries, between regions and between urban and rural areas. We postulated its effect would also vary by micro-geographic locations (indicated by mountain areas, plain areas and the edge areas) in a Chinese minority area.Methods
A cross-sectional study was conducted with a multistage random sample of 1474 school children aged 5-12 years in Guyuan, China. Child nutritional status was measured by height-for-age z scores (HAZ). Linear mixed models were used to examine its association with place of residence and maternal education.Results
Micro-geographic disparities in child nutritional status and the level of socioeconomic composition were found. Children living in mountain areas had poorer nutritional status, even after adjusting for demographic (plain versus mountain, β = 0.16, P = 0.033; edge versus mountain, β = 0.29, P = 0.002) and socioeconomic factors (plain versus mountain, β = 0.12, P = 0.137; edge versus mountain, β = 0.25, P = 0.009). The disparities significantly widened with increasing years of mothers’ schooling (maternal education*plain versus mountain: β = 0.06, P = 0.007; maternal education*edge versus mountain: β = 0.07, P = 0.005). Moreover, the association between maternal education and child nutrition was negative (β = -0.03, P = 0.056) in mountain areas but positive in plain areas (β = 0.02, P = 0.094) or in the edge areas (β = 0.04, P = 0.055).Conclusions
Micro-geographic disparities in child nutritional status increase with increasing level of maternal education and the effect of maternal education varies by micro-geographic locations, which exacerbates child health inequity. Educating rural girls alone is not sufficient; improving unfavorable conditions in mountain areas might make such investments more effective in promoting child health. Nutrition programs targeting to the least educated groups in plain and in edge areas would be critical to their cost-effectiveness. 相似文献15.
Zhenju Song Yuanlin Song Jun Yin Yao Shen Chenling Yao Zhan Sun Jinjun Jiang Duming Zhu Yong Zhang Qinjun Shen Lei Gao Chaoyang Tong Chunxue Bai 《PloS one》2012,7(9)
Background
Tumor necrosis factor (TNF) and TNF receptor superfamily (TNFR)-mediated immune response play an essential role in the pathogenesis of severe sepsis. Studies examining associations of TNF and lymphotoxin-α (LTA) single nucleotide polymorphisms (SNPs) with severe sepsis have produced conflicting results. The objective of this study was to investigate whether genetic variation in TNF, LTA, TNFRSF1A and TNFRSF1B was associated with susceptibility to or death from severe sepsis in Chinese Han population.Methodology/Principal Findings
Ten SNPs in TNF, LTA, TNFRSF1A and TNFRSF1B were genotyped in samples of patients with severe sepsis (n = 432), sepsis (n = 384) and healthy controls (n = 624). Our results showed that rs1800629, a SNP in the promoter region of TNF, was significantly associated with risk for severe sepsis. The minor allele frequency of rs1800629 was significantly higher in severe sepsis patients than that in both healthy controls (Padj = 0.00046, odds ratio (OR)adj = 1.92) and sepsis patients (Padj = 0.002, ORadj = 1.56). Further, we investigated the correlation between rs1800629 genotypes and TNF-α concentrations in peripheral blood mononuclear cells (PBMCs) of healthy volunteers exposed to lipopolysaccharides (LPS) ex vivo, and the association between rs1800629 and TNF-α serum levels in severe sepsis patients. After exposure to LPS, the TNF-α concentration in culture supernatants of PBMCs was significantly higher in the subjects with AA+AG genotypes than that with GG genotype (P = 0.007). Moreover, in patients with severe sepsis, individuals with AA+AG genotypes had significantly higher TNF-α serum concentrations than those with GG genotype (Padj = 0.02). However, there were no significant associations between SNPs in the four candidate genes and 30 day mortality for patients with severe sepsis.Conclusions/Significance
Our findings suggested that the functional TNF gene SNP rs1800629 was strongly associated with susceptibility to severe sepsis, but not with lethality in Chinese Han population. 相似文献16.
Haruki Momma Kaijun Niu Yoritoshi Kobayashi Cong Huang Atsushi Otomo Masahiko Chujo Hiroko Tadaura Ryoichi Nagatomi 《PloS one》2014,9(4)
Background
Post-traumatic stress disorder (PTSD) is a common psychological problem following natural disasters. Although pre-disaster risk factors are important for early detection and proactive support, the examination of such has been limited to sociodemographic factors, which were largely unaffected by the disasters. We examined the association between pre-disaster physical functioning and lifestyle and PTSD symptoms five months after the earthquake in the Great East Japan Earthquake survivors who were participating in a pre-existing cohort study.Methods
We designed a retrospective cohort study of a cooperative association in Sendai from August 2010 to August 2011. In 2010, lifestyle, physical condition, and sociodemographic factors were examined by self-reported questionnaires completed by 522 employees of this organization. We also measured the leg extension power of all the participants. PTSD symptoms were evaluated by the Japanese version of the Impact of Event Scale-Revised (IES-R-J) following the earthquake of 2011.Results
In multivariate linear regression analysis, leg extension power (β = –0.128, P = 0.025), daily drinking (β = 0.203, P = 0.006), and depressive symptoms (β = 0.139, P = 0.008) were associated with total score of the IES-R-J among men. Moreover, for the IES-R-J subscale, leg extension power was also negatively associated with Intrusion (β = –0.114, P = 0.045) and Hyperarousal (β = –0.163, P = 0.004) after adjusting for all other significant variables. For women, hypertension (β = 0.226, P = 0.032) and depressive symptoms (β = 0.205, P = 0.046) were associated with the total score of the IES-R-J.Conclusions
Leg extension power is a potentially modifiable pre-disaster risk factor among men for attenuating the severity of PTSD symptoms associated with great disasters such as the Great East Japan Earthquake among men. 相似文献17.
Bonnie R. Joubert Nora Franceschini Victor Mwapasa Kari E. North Steven R. Meshnick 《PloS one》2010,5(2)
Background
Human promoter polymorphisms in the chemokine co-receptor 5 gene (CCR5) have been noted for association with mother-to-child transmission of HIV (HIV MTCT) as well as reduced receptor expression in vitro, but have not been clearly associated with CCR5 expression in vivo. Placental expression of CCR5 may be influenced by such polymorphisms as well as other in vivo regulatory factors.Methodology/Principal Findings
We evaluated the associations between infant CCR5 polymorphisms, measures of maternal infection, and placental expression of CCR5 among mother-infant pairs in Blantyre, Malawi. RNA was extracted from placental tissue and used in multiplex real-time PCR to quantify gene expression. Through linear regression, we observed that CCR5-2554T (β = −0.67, 95% CI = −1.23, −0.11) and -2132T (β = −0.75, 95% CI = −0.131, −0.18) were significantly associated with reduced placental expression of CCR5. An incremental increase in CCR5 expression was observed for incremental increases in expression of two heparan sulfate genes involved in viral infection, HS3ST3A1 (β = 0.27, 95% CI = 0.18, 0.35) and HS3ST3B1 (β = 0.11, 95% CI = 0.06, 0.18). Among HIV infected mothers, an incremental increase in maternal HIV viral load was also associated with higher CCR5 expression (β = 0.76, 95% CI = 0.12, 1.39). Maternal HIV status had no overall effect (β = 0.072, 95% CI = −0.57, −0.72). Higher CCR5 expression was observed for mothers with malaria but was not statistically significant (β = 0.37, 95% CI = −0.43, 1.18).Conclusions/Significance
These results provide in vivo evidence for genetic and environmental factors involved in the regulation of CCR5 expression in the placenta. Our findings also suggest that the measurement of placental expression of CCR5 alone is not an adequate indicator of the risk of mother-to-child transmission of HIV. 相似文献18.
Purpose
To evaluate intraocular lens (IOL) tilt and decentration by anterior segment optical coherence tomography (AS-OCT) using 3-dimensional (3D) reconstruction method.Design
Prospective observational case series.Participants
Thirty-nine patients (39 eyes) were included.Methods
The IOL positions of all eyes were examined by AS-OCT. Images were obtained in 4 axes (0–180 degrees, 45–225 degrees, 90–270 degrees, and 135–315 degrees) using the quadrant-scan model. The cross-sectional images were analyzed with MATLAB software.Main Outcome Measures
The angle (θ) between the reference pupillary plane and the IOL plane, the distances between the center points of the pupil circle and the IOL on the x-axis (dx) and y-axis (dy) and the spatial distance (ds) were calculated after 3D-reconstruction.Results
The mean angle (θ) between the pupillary plane and the IOL plane was 2.94±0.99 degrees. The mean IOL decentration of dx and dy was 0.32±0.26 mm and 0.40±0.27 mm, respectively. The ds of the IOL decentration was 0.56±0.31 mm. There was no significant correlation between the ocular residual astigmatism (ORA) and the tilted angle or the decentration distance. There was a significant correlation between the ORA and total astigmatism (r = 0.742, P<0.001). There was no significant correlation between the postoperative best corrected visual acuity (BCVA) and the ORA (r = 0.156; P = 0.344), total astigmatism (r = 0.012; P = 0.942), tilted angle (θ; r = 0.172; P = 0.295) or decentration distance (dx: r = 0.191, P = 0.244; dy: r = 0.253, P = 0.121; ds: r = 0.298, P = 0.065).Conclusions
AS-OCT can be used as an alternative for the analysis of IOL tilt and decentration using 3D-reconstruction. 相似文献19.
Kensaku Aihara Tomohiro Handa Toru Oga Kizuku Watanabe Kiminobu Tanizawa Kohei Ikezoe Yoshio Taguchi Hiroe Sato Kazuo Chin Sonoko Nagai Shuh Narumiya Athol U. Wells Michiaki Mishima 《PloS one》2013,8(6)
Background
Idiopathic pulmonary fibrosis (IPF) is a devastating lung disease of unknown etiology with few current treatment options. Recently, we determined an important role of prostaglandin F2α (PGF2α) in pulmonary fibrosis by using a bleomycin-induced pulmonary fibrosis model and found an abundance of PGF2α in bronchoalveolar lavage fluid of IPF patients. We investigated the role of PGF2α in human IPF by assessing plasma concentrations of 15-keto-dihydro PGF2α, a stable metabolite of PGF2α.Methods
We measured plasma concentrations of 15-keto-dihydro PGF2α in 91 IPF patients and compared these values with those of controls (n = 25). We further investigated the relationships of plasma 15-keto-dihydro PGF2α concentrations with disease severity and mortality.Results
Plasma concentrations of 15-keto-dihydro PGF2α were significantly higher in IPF patients than controls (p<0.001). Plasma concentrations of this metabolite were significantly correlated with forced expiratory volume in 1 second (Rs [correlation coefficient] = −0.34, p = 0.004), forced vital capacity (Rs = −0.33, p = 0.005), diffusing capacity for carbon monoxide (Rs = −0.36, p = 0.003), the composite physiologic index (Rs = 0.40, p = 0.001), 6-minute walk distance (Rs = −0.24, p = 0.04) and end-exercise oxygen saturation (Rs = −0.25, p = 0.04) when patients with emphysema were excluded. Multivariate analysis using stepwise Cox proportional hazards model showed that a higher composite physiologic index (relative risk = 1.049, p = 0.002) and plasma 15-keto-dihydro PGF2α concentrations (relative risk = 1.005, p = 0.002) were independently associated with an increased risk of mortality.Conclusions
We demonstrated significant associations of plasma concentrations of PGF2α metabolites with disease severity and prognosis, which support a potential pathogenic role for PGF2α in human IPF. 相似文献20.
Qian Zhang Yan Chen Bin Zhang Bin Shi Wenjun Weng Zhipeng Chen Nannan Guo Yibing Hua Lingjun Zhu 《PloS one》2013,8(8)