C677T mutation of methylenetetrahydrofolate reductase gene and serum homocysteine levels in Turkish patients with coronary artery disease

Elevated levels of homocysteine is a risk factor for coronary artery disease. The C677T transition in methylenetetrahydrofolate reductase (MTHFR) is associated with increased homocysteine levels in the general population. We analysed the association between the MTHFR C677T polymorphism and serum homocysteine concentrations in patients with coronary artery disease (CAD). Allele frequencies for the 'C' (wild-type) and 'T' alleles were 0.71 and 0.29 in CAD patients and 0.70 and 0.30 in controls, respectively. There was no difference in the distribution of MTHFR genotypes between patients with CAD and control subjects (p > 0.05). In the patient group, homocysteine levels were higher than controls but not significantly (13.99 +/- 7.44 vs. 11.77 +/- 5.18 micromol l(-1); p > 0.05). Serum homocysteine concentration was significantly higher in the TT genotype with respect to CC and CT genotypes in both the control group (p < 0.01) and patient group (p < 0.01). Systolic and diastolic blood pressures in subjects with different MTHFR genotypes did not differ significantly. In conclusion, MTHFR C677T mutation was significantly related to hyperhomocysteinemia. In spite of the clear effect of the MTHFR polymorphism on elevated homocysteine levels, we did not observe any associations among the MTHFR genotypes with a the risk of CAD in the Turkish population.     

Low serum zinc levels in patients undergoing coronary angiography correlate with immune activation and inflammation

IntroductionLow serum zinc concentrations are associated with adverse outcomes. To explain this phenomenon we aimed to investigate whether low zinc levels are related to immune activation, renal function and coronary artery disease (CAD).MethodsSerum concentrations of zinc and the immune activation markers neopterin and C-reactive protein (CRP) were measured in 2048 patients derived from the LUdwigshafen RIsk and Cardiovascular Health (LURIC) study, a cohort study among patients referred for coronary angiography.ResultsZinc concentrations did not differ between patients with CAD (mean ± SD: 13.3 ± 2.4 μmol/L) and controls (13.3 ± 2.2 μmol/L; Welch's t test: p = n.s.) but CAD patients had higher neopterin (8.6 ± 7.4 nmol/L) and CRP (9.7 ± 19.6 mg/L) concentrations compared to controls (neopterin: 7.5 ± 4.8 nmol/L, p = 0.0005; CRP: 5.5 ± 10.0 mg/L, p < 0.0001). There was an inverse correlation between serum zinc concentrations and neopterin (Spearman's rank correlation: r_s = ?0.222) and CRP (r_s = ?0.166; both p < 0.0001) concentrations.ConclusionsOur results indicate increased inflammatory processes in patients with low zinc levels. Further studies should clarify whether inflammation related processes such as renal wasting contribute to zinc deficiency and underlie the adverse health consequences of low serum zinc levels.     

Association of serum bilirubin with contrast-induced nephropathy and future cardiovascular events in patients undergoing coronary intervention

Objectives

Enhanced reactive oxygen species formation within the kidney following the administration of contrast media may play a key role in the development of contrast-induced nephropathy (CIN). Bilirubin has emerged as an important endogenous antioxidant molecule. This study was undertaken to determine whether bilirubin is associated with CIN and future cardiovascular events in patients undergoing coronary intervention.

Methods

Totally, 544 consecutive patients received coronary intervention were enrolled. All patients were followed up for at least 3 years or until the occurrence of a major event. The primary endpoint was CIN, defined as a rise in serum creatinine (SCr) of 0.5 mg/dl or a 25% increase from the baseline value within 48 hours after the procedure. The secondary endpoint was the combined occurrence of major adverse cardiovascular events (MACE), including death, nonfatal myocardial infarction, and ischemic stroke.

Results

Overall, CIN occurred in 85 (15.6%) patients. All patients were stratified into 3 groups (low/normal/high) according to the serum bilirubin levels. In a multivariate logistic analysis, the odds ratio for CIN with low-bilirubin levels relative to high-bilirubin levels was 11.82 (95% CI, 3.25–43.03). By Cox regression analysis, serum bilirubin levels was an independent predictor of MACE in patients undergoing coronary intervention (low vs. high hazard ratio 2.26; 95% CI, 1.05–4.90).

Conclusions

CIN is a serious complication of coronary intervention. Higher serum bilirubin concentrations were associated with lower risk of CIN and fewer cardiovascular events. The development of interventions that promote bilirubin levels may be a potential target to reduce CIN and future MACE in patients undergoing coronary intervention.     

冠心病患者幽门螺杆菌感染与血清Ghrelin、同型半胱氨酸水平的相关性研究

目的探讨冠心病患者幽门螺杆菌(Helicobacter pylori,H.pylori)感染与血清Ghrelin、同型半胱氨酸(Hcy)水平的相关性。方法选择2013年1月至2014年12月行冠状动脉造影确诊冠心病患者136例作为冠心病组,另选择同期健康体检人员60例作为对照组。运用14 C尿素呼气试验方法测定H.pylori感染情况,观察组患者的冠状动脉病变程度进行Gensini评分,测定血清Ghrelin和Hcy水平,分析H.pylori感染与Ghrelin、Hcy水平及Gensini积分之间的关系。结果冠心病组血清Ghrelin水平明显低于对照组,差异有统计学意义(t=10.65,P0.05);冠心病组血清Hcy水平明显高于对照组,差异有统计学意义(t=6.08,P0.05)。冠心病患者中,H.pylori感染组血清Ghrelin明显低于H.pylori未感染组,差异有统计学意义(t=7.58,P0.05);H.pylori感染组组血清Hcy明显高于H.pylori未感染组,差异有统计学意义(t=5.63,P0.05)。随着冠心病H.pylori感染程度的加重,血清Ghrelin水平逐渐下降,血清Hcy水平、Gensini积分逐渐升高。H.pylori感染根治后血清Ghrelin水平较治疗前明显升高,而Hcy水平明显下降,差异均有统计学意义(t=14.84、6.25,P0.05)。结论 H.pylori感染能够影响冠心病患者血清Ghrelin、Hcy水平,H.pylori感染可能参与冠心病发生发展。H.pylori感染程度与冠心病患者冠状动脉病变程度相关。     

Major genes regulating total serum immunoglobulin E levels in families with asthma

Immunoglobulin E (IgE) has a major role in the pathogenesis of allergic disorders and asthma. Previous data from 92 families, each identified through a proband with asthma, showed evidence for two major genes regulating total serum IgE levels. One of these genes mapped to 5q31-33. In the current study, the segregation analysis was extended by the addition of 108 probands and their families, ascertained in the same manner. A mixed recessive model (i.e., major recessive gene and residual genetic effect) was the best-fitting and most-parsimonious one-locus model of the segregation analysis. A mixed two-major-gene model (i.e., two major genes and residual genetic effect) fit the data significantly better than did the mixed recessive one-major-gene model. The second gene modified the effect of the first recessive gene. Individuals with the genotype aaBB (homozygous high-risk allele at the first gene and homozygous low-risk allele at the second locus) had normal IgE levels (mean 23 IU/ml), and only individuals with genotypes aaBb and aabb had high IgE levels (mean 282 IU/ml). A genomewide screening was performed using variance-component analysis. Significant evidence for linkage was found for a novel locus at 7q, with a multipoint LOD score of 3. 36 (P=.00004). A LOD score of 3.65 (P=.00002) was obtained after genotyping additional markers in this region. Evidence for linkage was also found for two previously reported regions, 5q and 12q, with LOD scores of 2.73 (P=.0002) and 2.46 (P=.0004), respectively. These results suggest that several major genes, plus residual genetic effects, regulate total serum IgE levels.     

Mutational analysis of gene families in human cancer

The completion of the human genome project has marked a new beginning in biomedical sciences. Human cancer is a genetic disease and, accordingly, the field of oncology has been one of the first to be impacted by this historic revolution. Knowledge of the sequence and organization of the human genome facilitates the systematic analysis of the genetic alterations underlying the origin and evolution of tumors. Recent mutational analyses in colorectal and other cancers have focused on examination of gene families involved in signal transduction, such as kinases and phosphatases. This approach has been successful in identifying mutations in a variety of different genes, including the identification of PI3KCA as one of the most commonly mutated oncogenes in human cancer. Such genomic analyses have already demonstrated their utility in basic and clinical cancer research, and are expected to have an important impact on future diagnostic and therapeutic strategies.     

Phylogenetic analysis reveals gene conversions in multigene families of rhizobia

Gene families are an important and intrinsic trait of rhizobial species. These gene copies can participate in non-reciprocal recombination events, also called gene conversions. Gene conversion has diverse roles, but it is usually implicated in the evolution of multigene families. Here, we searched for gene conversions in multigene families of six representative rhizobial genomes. We identified 11 gene families with different numbers of copies, genome location and function in CFN42 and CIAT652 strains of Rhizobium etli, Rhizobium sp NGR234, Mesorhizobium loti MAFF303099, Sinorhizobium meliloti 1021, and Bradyrhizobium japonicum USDA110. Gene conversions were detected by phylogenetic inference in the nifD and nifK gene families in R. etli. Sequence analysis confirmed multiple gene conversions in these two gene families. We suggest that gene conversion events have an important role in homogenizing multigene families in rhizobia.     

草地贪夜蛾解毒代谢相关基因家族的进化分析

近年来草地贪夜蛾Spodoptera frugiperda在世界各地猖獗为害,其寄主范围广,且已对多种化学药剂和转Bt玉米产生抗性。本文对包括草地贪夜蛾在内的14种昆虫进行了解毒代谢相关基因家族的注释,在草地贪夜蛾中发现了152个细胞色素P450(cytochrome p450,P450)、92个ABC转运蛋白(ATP-binding cassette transporter,ABC transporter)、44个谷胱甘肽转移酶(glutathione s-transferase,GST)以及39个尿苷二磷酸葡萄糖醛酸转移酶(UDP-glucuronosyl-transferase,UGT)。与其他鳞翅目物种相比,草地贪夜蛾的P450和GST基因数量最多,其中152个P450基因可被归类至Mito、CYP2、CYP3和CYP4四个簇中;Mito和CYP2簇的P450基因总数与家蚕Bombyx mori相近,但CYP3和CYP4簇的P450基因明显多于家蚕,进化分析结果显示CYP3和CYP4簇的P450基因发生了明显的扩增;与家蚕P450基因的共线性分析发现草地贪夜蛾89个P450基因在其基因组上呈簇分布并发生了簇的扩增;与家蚕相比,GST和ABC转运蛋白家族基因的数量明显增多。UGT基因家族没有明显增加,但在基因进化分析中有成簇现象,表明可能存在近期的扩增事件。本研究首次从基因组水平鉴定了草地贪夜蛾解毒代谢相关基因家族,对理解草地贪夜蛾的生物学特性及抗性的形成具有重要指导意义。     

Incidence and severity of coronary artery disease in patients with atrial fibrillation undergoing first-time coronary angiography

Background

In standard reference sources, the incidence of coronary artery disease (CAD) in patients with atrial fibrillation (AF) ranged between 24 and 46.5%. Since then, the incidence of cardiovascular risk factors (CRF) has increased and modern treatment strategies (“pill in the pocket”) are only applicable to patients without structural heart disease. The aim of this study was to investigate the incidence and severity of CAD in patients with AF.

Methods

From January 2005 until December 2009, we included 261 consecutive patients admitted to hospital with paroxysmal, persistent or permanent AF in this prospective study. All patients underwent coronary angiography and the Framingham risk score (FRS) was calculated. Patients with previously diagnosed or previously excluded CAD were excluded.

Results

The overall incidence of CAD in patients presenting with AF was 34%; in patients >70 years, the incidence of CAD was 41%. The incidence of patients undergoing a percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) was 21%. Patients with CAD were older (73±8 years vs 68±10 years, p = 0.001), had significantly more frequent hypercholesterolemia (60% vs 30%, p<0.001), were more frequent smokers (26% vs 13%, p = 0.017) and suffered from angina more often (37% vs 2%, p<0.001). There was a significant linear trend among the FRS categories in percentage and the prevalence of CAD and PCI/CABG (p<0.0001).

Conclusions

The overall incidence of CAD in patients presenting with AF was relatively high at 34%; the incidence of PCI/CABG was 21%. Based upon increasing CRF in the western world, we recommend a careful investigation respecting the FRS to either definitely exclude or establish an early diagnosis of CAD – which could contribute to an early and safe therapeutic strategy considering type Ic antiarrhythmics and oral anticoagulation.     

葡萄生长素响应基因家族生物信息学鉴定和表达分析

生长素响应基因家族能调节植物体内生长素平衡和生长素信号途径。文章采用生物信息学方法检索获得葡萄(Vitisvinifera L.)基因组数据库中的生长素响应基因,通过分析其染色体定位、基因共线性和系统进化,发现葡萄基因组含有25个AUX_IAA基因、19个ARF基因、9个GH3基因、42个LBD基因。这些生长素响应基因不均匀分布在葡萄的19条染色体上,部分家族基因在染色体上形成基因簇。葡萄芯片数据结果表明,生长素响应基因在葡萄不同时期的果实和叶芽中均有表达,尤其在果实转色期、叶芽萌发或休眠期表达量急剧变化。研究结果为葡萄生长素响应基因在叶片和果实发育过程中的功能研究提供参考。     

Elevated homocysteine level and prognosis in patients with acute coronary syndrome: a meta-analysis

Objective: Controversial results exist with respect to the association between elevated homocysteine level and adverse prognosis in acute coronary syndrome (ACS) patients. We performed a meta-analysis to evaluate the prognostic value of homocysteine level on ACS patients.

Materials and methods: A comprehensive literature search of PubMed and Embase databases was conducted prior to August 2018. Prospective observational studies reporting the association of baseline homocysteine level with major adverse cardiovascular events (MACE), cardiovascular or all-cause mortality in ACS patients were selected. Pooled risk ratio (RR) and corresponding 95% confidence intervals (CI) were calculated for the highest versus the lowest homocysteine level.

Results: Ten studies including 4120 ACS patients were identified. ACS patients with the highest homocysteine level had an increased risk of MACE (RR 2.01; 95% CI 1.53–2.64) and all-cause mortality (RR 2.05; 95% CI 1.50–2.79) after controlling confounding factors. However, the association between elevated homocysteine level and cardiovascular mortality (RR 1.08; 95% CI 0.83–1.39) was not statistically significant.

Conclusions: Elevated homocysteine level was associated with an increased risk of MACE and all-cause mortality among ACS patients. However, the association of elevated homocysteine level with cardiovascular mortality in ACS patients should be further confirmed in future studies.     

脑梗死患者同型半胧氨酸与血脂相关性的研究

目的：研究脑梗死患者空腹血浆总同型半胱氨酸（THCY）水平及其与血脂的关系。方法：观察组（54例）均为我院2002年1月．2006年5月住院脑梗死患者,测定空腹THCY水平及血脂各参数;另有同龄健康者为对照组（39例）,进行比较分析。结果：观察组与对照组比较,空腹THCY水平差异有统计学意义（P〈0．05）,血浆HCY含量与TC、TG、HDL-C、LDL-C含量的相关性均无统计学意义。结论：高HCY血症与血脂无关,是脑梗死的独立危险因素之一。     

Multielement analysis in serum of thyroid cancer patients before and after a surgical operation

Concentrations of trace elements Zn, Cu, Fe, Mn, Mg, and Sr in the serum of 50 thyroid cancer patients and 50 healthy controls were analyzed comprehensively by Pattern Recognition Analysis Method. Based on the Principal Component Analysis Method, Zn, Cu, and Sr were found to be the principal elements with significant variations between patients and healthy controls. According to the Mahalanolis Distance Decision and Nonlinear Mapping Methods, the trace elements levels in the serum of cancerous patients were found significantly different from that of controls. For 16 thyroid malignant tumor patients who underwent surgery, sample points of patients after surgery were directional away from corresponding points before surgery. However, an overlapping was found and separation between two groups of points was not complete. This finding suggests that there may be a latency period for the restoration of trace element levels after removal of the malignant tumorous tissue.     

草地贪夜蛾化学感受相关基因家族的进化分析

草地贪夜蛾Spodoptera frugiperda于今年1月首次在我国发现以来,已迅速扩散到长江流域省份,对我国玉米生产造成重大危害。本文从全基因组水平对草地贪夜蛾化学感受相关基因进行了鉴定和进化分析。获得了54个气味结合蛋白(odorant binding proteins,OBP)、15个化学感受蛋白(chemosensory proteins,CSP)、82个气味受体(odorant receptors,OR)、210个味觉受体(gustatory receptors,GR)、44个离子型受体(ionotropic receptors,IR)和13个感受神经元膜蛋白(sensory neuron membrane proteins,SNMP)基因。进化分析发现,与家蚕相比,草地贪夜蛾OBP与GR基因具有明显的扩增现象,但SNMP基因存在轻微的收缩。本研究首次从基因组水平鉴定了草地贪夜蛾化学感受相关基因,为进一步开展该物种的相关研究奠定了基础。     

Temporal characterization of serum metabolite signatures in lung cancer patients undergoing treatment

Lung cancer causes more deaths in men and women than any other cancer related disease. Currently, few effective strategies exist to predict how patients will respond to treatment. We evaluated the serum metabolomic profiles of 25 lung cancer patients undergoing chemotherapy ± radiation to evaluate the feasibility of metabolites as temporal biomarkers of clinical outcomes. Serial serum specimens collected prospectively from lung cancer patients were analyzed using both nuclear magnetic resonance (¹H-NMR) spectroscopy and gas chromatography mass spectrometry (GC–MS). Multivariate statistical analysis consisted of unsupervised principal component analysis or orthogonal partial least squares discriminant analysis with significance assessed using a cross-validated ANOVA. The metabolite profiles were reflective of the temporal distinction between patient samples before during and after receiving therapy (¹H-NMR, p < 0.001: and GC–MS p < 0.01). Disease progression and survival were strongly correlative with the GC–MS metabolite data whereas stage and cancer type were associated with ¹H-NMR data. Metabolites such as hydroxylamine, tridecan-1-ol, octadecan-1-ol, were indicative of survival (GC–MS p < 0.05) and metabolites such as tagatose, hydroxylamine, glucopyranose, and threonine that were reflective of progression (GC–MS p < 0.05). Metabolite profiles have the potential to act as prognostic markers of clinical outcomes for lung cancer patients. Serial ¹H-NMR measurements appear to detect metabolites diagnostic of tumor pathology, while GC–MS provided data better related to prognostic clinical outcomes, possibility due to physiochemical bias related to specific biochemical pathways. These results warrant further study in a larger cohort and with various treatment options.