贵州三个少数民族谷胱甘肽S-转移酶M1、T1和P1基因多态性

目的研究贵州省从江县侗族、威宁县彝族、荔波县瑶族的谷胱甘肽S-转移酶基因(GSTs)多态性。方法在隔离自然人群(从江县侗族108人、威宁县彝族104人、荔波县瑶族109人)中,采用多重等位基因特异聚合酶链反应方法分析GSTM1和GSTT1基因多态性,采用聚合酶链反应及限制性片段长度多态性方法分析GSTP11578(A→G)基因多态性。结果贵州省从江县侗族、威宁县彝族、荔波县瑶族的GSTM1和GSTT1纯合缺失基因型频率分别为59.6%～71.2%、39.4%～72.5%。其GSTP11578(A→G)基因型频率分别是:AA为63.3%～75%、AG为23.2%～35.8%、GG为0～1.9%。等位基因频率:A为81.2%～86.6%,G为13.4%～18.8%。结论GSTT1基因型频率在贵州从江侗族、威宁彝族、荔波瑶族中存在差异,其分布特征可能与人群中不同种族以及同一种族不同民族相关。     

Association between glutathione S-transferase gene M1 and T1 polymorphisms and chronic obstructive pulmonary disease risk: A meta-analysis

Chronic obstructive pulmonary disease (COPD) is a severe lung disease characterized by long-term breathing problems. A series of studies have indicated that the glutathione S-transferase genes M1 and T1 are associated with COPD susceptibility; however, the result still remains inconclusive. This meta-analysis was performed to estimate the effect of GSTM1 and GSTT1 polymorphisms in COPD risk. Eligible case-control studies published between January 2000 and December 2017 was searched and retrieved. A total of 37 articles were screened out, including 4674 COPD patients and 5006 controls. Overall, our results found that GSTM1 and GSTT1 null genotypes significantly increased the risk of COPD (GSTM1: odds ratio [OR] = 1.52, 95% confidence interval [CI] = 1.31-1.77, P <.00001; GSTT1: OR = 1.28, 95% CI = 1.09-1.50, P = .003). Subgroup analysis by ethnicity suggested that there was a close association between GSTM1 null polymorphism and COPD susceptibility in each studied ethnicity, while GSTT1 null polymorphism only showed association with Asian COPD patients. Moreover, we also found that joint GSTM1/GSTT1 null genotypes showed a high association with increased COPD susceptibility (OR = 1.42, 95% CI = 1.21-1.66, P < .0001). In conclusion, our results indicated that GSTM1 null, GSTT1 null, and the combined GSTM1/GSTT1 null genotypes might be risk factors in the development of COPD. However, future case-control studies with large-scale participants are still required to further estimate these associations.     

GSTM1, GSTT1 and GSTP1 polymorphisms in the Korean population

The isoenzymes of the glutathione s transferase (GST) family play a vital role in phase II of biotransformation of many substances. Using a multiplex polymerase chain reaction and a direct sequencing analysis, the frequencies of GSTM1, GSTT1, and GSTP1 polymorphisms were evaluated in 1,051 Korean male subjects. We found that 53.8% of the individuals had the GSTM1 null genotype and 54.3% had the GSTT 1 null genotype. The genotypic distribution of GSTP1 was Ile105/Ile105 in 68.4%, Ile105/Val105 in 29.1% and Val105/Va105 in 2.5%. The most frequently observed combination of GSTM1, GSTP1 and GSTT1 genotypes was Null type/Ile105/Ile105/Null type, while the combination of Non-null type/Val105/Val105/Non-Null type was not observed. We found that the genotype distributions of three GST isoenzymes in the Koreans are similar to those reported in Asians and previously reported Koreans. We believe our results, which are represented by a large population, are reliable estimates of the frequencies of the polymorphic GST alleles in the Koreans and will help future researches on GST polymorphisms.     

Frequencies of glutathione s-transferase (GSTM1, GSTM3 AND GSTT1) polymorphisms in a Malaysian population

Introduction

Glutathione S-transferase (GST) is a xenobiotic metabolising enzyme (XME), which may modify susceptibility in certain ethnic groups, showing ethnic dependent polymorphism. The aim of this study was to determine GSTM1, GSTM3 and GSTT1 gene polymorphisms in a Malaysian population in Kuala Lumpur.

Material and methods

Blood or buccal swab samples were collected from 137 Form II students from three schools in Wilayah Persekutuan Kuala Lumpur. Genotyping was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).

Results

Glutathione-S-transferase GSTM3 gene frequencies were 89% for AA, 10% for AB and 1% for BB. The gene frequencies for deleted GSTM1 and GSTT1 were 66% and 18% respectively.

Conclusions

This study suggested that the Malay population is at risk for environmental diseases and provides the basis for gene-environment association studies to be carried out.     

Severe chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) exacts a heavy toll on society, yet its prevention, diagnosis and treatment receives inadequate attention from both the medical community and from society at large. Guidelines released in 2001 from the Global Initiative for Chronic Obstructive Lung Disease (GOLD) are aimed at redressing this inequity. In this review, we integrate information from the GOLD guidelines with recent updates on the prevention, treatment and management as related specifically to the most severe form of this disease. In order to help distinguish COPD from other disorders that may mimic or confound its treatment, we place particular emphasis on the definition, underlying pathophysiology and diagnosis of COPD. In addition, we discuss future directions in pharmacotherapy.     

Left heart function in chronic obstructive lung disease

Summary In patients with varying degrees of chronic obstructive pulmonary disease (COPD), simultaneous measurements of central hemodynamics and left ventricular radionuclide ventriculograms at rest and during exercise were made. In 21 of these patients, satisfactory echocardiograms could be performed. In seven of the patients, arterial blood pressure at rest was increased. Decreased compliance of the left ventricle was thought to be present in patients with COPD and additional arterial hypertension. The left ventricular ejection fraction (LVEF) at rest was in the high normal range in all patients. During exercise, no further increase was observed. This pattern of LVEF response seems to be typical in patients with COPD. Because the highest values were observed in the more severe COPD and right ventricular hypertrophy, it is unlikely that an impairment of left ventricular function is caused by COPD. In five of 27 patients, an abnormal decrease of LVEF and regional hypokinesis occurred during exercise, thus suggesting additional coronary heart disease. The fact that at least 30% of the patients with COPD suffered from arterial hypertension and 20% of the patients exhibited unexpected ischemia detected by regional hypokinesis in RNV during exercise, but not in the ECG, may be of practical relevance. Coronary angiography was not indicated because most of these patients were over 65 and the factor limiting the working capacity was ventilatory impairment and not angina pectoris, in all patients. For this reason, a diagnostic uncertainty remains with regard to additional coronary heart disease in the older patients with advanced chronic obstructive pulmonary disease.Lung Function Parameters VC (1) inspiratory vital capacity - FEV1 (1) forced exspiratory volume in 1 sec - Raw (cmH20/l/s) airways resistance - RV/TLC (%) residual volume/total lung capacity - paO₂ (mm Hg) O₂ partial pressure Hemodynamic Parameters CI (1/min/sqm) cardiac index - SVI (ml/sqm) stroke volume index - PAP (mm Hg) pulmonary artery mean pressure - PwP (mm Hg) pulmonary capillary wedge pressure - RRs (mm Hg) systolic arterial pressure - RRd (mm Hg) diastolic arterial pressure (at the time of catheterization) - RR(WHO) (mm Hg) mean values measured at different days (at least 3 values). Parameters Derived from Combined Radionuclide Ventriculography and Central Hemodynamics LVEF (%) left ventricular ejection fraction - LVESVI (ml/sqm) left ventricular endsystolic volume index - P/V (mm Hg/ml/sqm) peak systolic pressure/endsystolic volume index - PFR (1/sec) peak filling rate: endsystolic volume/sec Echocardiographic Parameters RV d wth (mm) right ventricular enddiastolic wall thickness - LV d wth (mm) left ventricular enddiastolic wall thickness In honor to Prof. W.E. Adam's 60th birthday     

Microsomal epoxide hydrolase (EPHX1) polymorphisms are associated with aberrant promoter methylation of ERCC3 and hematotoxicity in benzene‐exposed workers

Benzene is an important industrial chemical and widespread environmental pollutant known to induce leukemia and other blood disorders. To be carcinogenic, benzene must be metabolized to produce toxic metabolites. To investigate whether single nucleotide polymorphisms (SNPs) in the metabolic enzyme genes are associated with benzene‐induced alterations in DNA methylation and hematotoxicity, we genotyped four commonly studied SNPs in three metabolic enzymes genes CYP1A1, EPHX1 and NQO1; and analyzed promoter DNA methylation status in 11 genes which have been reported to be associated with benzene‐induced hematotoxicity (BLM, CYP1A1, EPHX1, ERCC3, NQO1, NUDT1, p15, p16, RAD51, TP53 and WRAP53) in 77 benzene‐exposed workers and 25 unexposed controls in China. ERCC3, a DNA repair gene, showed a small but statistically significant increase of promoter DNA methylation in the exposed group compared with the unexposed group (mean ± SD: 4.73 ± 3.46% vs. 3.63 ± 1.96%, P = 0.048). We also observed that an increased number of C allele for rs1051740 in EPHX1 was associated with decreased ERCC3 methylation levels in benzene‐exposed workers (P_trend = 0.001), but not in unexposed controls (P_trend = 0.379). Interestingly, another EPHX1 SNP (rs2234922) was associated with lower white blood cell (WBC) counts (P_trend = 0.044) in benzene‐exposed workers. These associations remained the same when ERCC3 promoter methylation and WBCs were dichotomized according to the 90th percentile (≥6%) of methylation levels in controls and a leucopenia cutoff (<4 × 10⁹/L), respectively. Our findings suggest that benzene exposure may be associated with hypermethylation in ERCC3, and that genetic variants in EPHX1 may play an important role in epigenetic changes and hematotoxicity among benzene‐exposed workers. Environ. Mol. Mutagen. 54:397–405, 2013. © 2013 Wiley Periodicals, Inc.     

Immune response in chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a major public health problem because of its high prevalence, rising incidence and associated socio-economic cost. The inhalation of toxic particles and gases, mostly tobacco smoke, is the main risk factor for COPD. Yet, not all smokers are equally susceptible to these toxic effects and only a percentage of them develop the disease (so-called ‘susceptible smokers’). This, in combination with the observation that COPD shows familial aggregation, suggests that the genetic background of the smoker is a key element in the pathogenesis of the disease. On the other hand, it is well established that ‘susceptible’ smokers exhibit an enhanced inflammatory response of the lung parenchyma as compared with ‘resistant’ smokers (i.e., those who manage to maintain lung function within the normal age range despite their habit). Importantly, in COPD patients this inflammatory response does not resolve after quitting smoking, again at variance with resistant smokers. All in all, these observations suggest that the pathogenesis of COPD may involve, in some patients, an autoimmune component which contributes to the enhanced and persistent inflammatory response that characterizes the disease. Here we: i) review briefly the pathobiology of COPD; ii) present the available scientific evidence supporting a potential role for autoimmunity in COPD; iii) propose a three-step pathogenic hypothesis in the transition from smoking to COPD; and iv) discuss potential implications for the diagnosis and treatment of this frequent, growing, devastating and costly disease.     

GSTM1、GSTT1缺失和GSTP1基因多态性与原发无精症的相关性研究

目的 探讨谷胱甘肽硫转移酶(glutathione S-transferase,GST)基因家族中GSTM1、GSTT1缺失和GSTP1多态性与汉族人群原发性无精子症的相关性.方法 采用病例对照研究的方法,应用多重PCR及PCR-限制性片段长度多态性技术检测236例汉族原发无精症患者和142名正常生育男性的GSTM1、GSTT1基因缺失和GSTP1基因(Ile/Val)多态性.结果 M1(-/-)和P1(Ile/Val或Val/Val)联合基因型在对照组中分布为24.65％(35/142),高于病例组的15.68％(37/236),差异有统计学意义(P=0.031);M1(-/-),T1(+/+)和P1(Ile/Val或Val/Val)联合基因型在对照组中分布为12.68％ (18/142),高于病例组的5.51％(13/236),差异有统计学意义(P=0.014).结论 M1(-/-)和P1(Ile/Val或Val/Val)联合基因型以及M1(-/-),T1(+/+)和P1(Ile/Val或Val/Val)联合基因型可能降低男性患无精症的风险.     

GSTM1, GSTT1, and GSTP1 genotypes and the genotoxicity of hydroquinone in human lymphocytes

Hydroquinone is a myelotoxin that is found in many foods and is also formed through the metabolism of benzene. Human exposure to benzene is associated with the development of myelodysplastic syndrome and acute myelogenous leukemia. Hydroquinone is genotoxic in several in vitro and in vivo test systems, inducing micronuclei (MN), sister-chromatid exchange (SCE), and chromosomal aberrations. Glutathione S-transferases (GSTs) are a superfamily of polymorphic enzymes involved in the conjugation of reactive chemical intermediates to soluble forms. These enzymes play a key role in the detoxification of endogenous and exogenous compounds, and the polymorphic genes GSTM1, GSTT1, and GSTP1 have been associated with the differential metabolism of several genotoxicants. In the present study, we have evaluated the effect of GSTM1, GSTT1, and GSTP1 polymorphisms on the frequency of MN and SCE induced by hydroquinone in human lymphocytes. Lymphocytes were obtained from 15 healthy non-smoking donors, and their GSTM1, GSTT1, and GSTP1 genotypes determined. Treatment of cultures of the lymphocytes with hydroquinone significantly increased the overall frequencies of MN and SCE (P<0.0001). Individuals with the GSTM1 null genotype had a significantly higher frequency of MN compared with GSTM1-present individuals (P=0.013); in contrast, the GSTM1 genotype had no effect on hydroquinone-induced SCE frequency. The other polymorphisms did not significantly affect the frequencies of MN or SCE. These results suggest that GSTM1 is involved in the metabolic fate of hydroquinone and that polymorphisms in GSTM1 could be related to inter-individual differences in DNA damage arising from the exposure to this compound.     

Th17细胞在慢性阻塞性肺疾病肺部炎症中的作用

由于长期吸烟的刺激,活化的辅助性T细胞17（Th17）能浸润到肺组织并参与肺泡壁的破坏及肺气肿的形成.Th17细胞在IL-23的作用下,分泌IL-17、IL-21、IL-22等多种细胞因子,其中IL-17可以促进气道中性粒细胞的募集和激活,IL-21在维持、增强Th17细胞的数量及功能的同时,能增加CD8＋细胞的数量及其细胞毒活性,在吸烟诱导的慢性阻塞性疾病（COPD）肺部连续炎症中发挥持续放大效应.在不同的炎症环境中,Th17细胞及其分泌的细胞因子与Th1细胞、调节性T细胞（Treg）以及多种参与固有免疫应答的细胞间相互作用和调节,共同参与COPD的发病,并构成了固有免疫与适应性免疫之间的桥梁.     

Neurophysiological aspects and their relationship to clinical and functional impairment in patients with chronic obstructive pulmonary disease

OBJECTIVE:

The purpose was to assess functional (balance L–L and A–P displacement, sit‐to‐stand test (SST) and Tinetti scale – balance and gait) and neurophysiological aspects (patellar and Achilles reflex and strength) relating these responses to the BODE Index.

INTRODUCTION:

The neurophysiological alterations found in patients with chronic obstructive pulmonary disease (COPD) are associated with the severity of the disease. There is also involvement of peripheral muscle which, in combination with neurophysiological impairment, may further compromise the functional activity of these patients.

METHODS:

A cross‐sectional study design was used. Twenty‐two patients with moderate to very severe COPD (>60 years) and 16 age‐matched healthy volunteers served as the control group (CG). The subjects performed spirometry and several measures of static and dynamic balance, monosynaptic reflexes, peripheral muscle strength, SST and the 6‐minute walk test.

RESULTS:

The individuals with COPD had a reduced reflex response, 36.77±3.23 (p<0.05) and 43.54±6.60 (p<0.05), achieved a lower number repetitions on the SST 19.27±3.88 (p<0.05), exhibited lesser peripheral muscle strength on the femoral quadriceps muscle, 24.98±6.88 (p<0.05) and exhibited deficits in functional balance and gait on the Tinetti scale, 26.86±1.69 (p<0.05), compared with the CG. The BODE Index demonstrated correlations with balance assessment (determined by the Tinetti scale), r = 0.59 (p<0.05) and the sit‐to‐stand test, r = 0.78 (p<0.05).

CONCLUSIONS:

The individuals with COPD had functional and neurophysiological alterations in comparison with the control group. The BODE Index was correlated with the Tinetti scale and the SST. Both are functional tests, easy to administer, low cost and feasible, especially the SST. These results suggest a worse prognosis; however, more studies are needed to identify the causes of these changes and the repercussions that could result in their activities of daily living.     

胸腺五肽辅助治疗慢性阻塞性肺病的疗效观察

目的观察胸腺五肽辅助治疗慢性阻塞性肺病(COPD)的疗效。方法将78例COPD患者随机分为2组,对照组给予常规治疗,治疗组加用胸腺五肽,观察比较2组患者症状体征缓解时间、平均住院时间以及3个月内再入院率。结果治疗组症状体征缓解时间、平均住院时间均较对照组显著缩短(P<0.05),治疗组3个月内再入院率较对照组显著降低(P<0.05)。结论胸腺五肽可增强COPD患者的免疫功能,缩短平均住院时间,降低再发风险,提高患者生活质量。     

SOX5基因多态性与慢性阻塞性肺疾病及并发症肺动脉高压的关联性分析

目的:通过观察慢性阻塞性肺疾病(COPD)稳定期患者、COPD合并肺动脉高压(PH)患者及健康者之间SOX5基因单核苷酸多态性(SNPs)的分布差异,初步探索SOX5基因多态性与COPD相关PH易感性的关联。方法:连续选择2013年4月~2015年4月就诊于宁夏人民医院总院及宁南分院呼吸内科的COPD稳定期患者250例,根据COPD诊治指南(2013年版)诊断标准入组,并且就诊当天全部进行超声心动图检查,根据肺动脉收缩压(PASP)结果分为COPD合并PH组(PASP≥50 mm Hg)103例和COPD非PH组(PASP50 mm Hg)147例。健康对照组选择同期在宁夏人民医院体检的健康者127例。使用Sequenom Mass ARRAY SNP检测系统检测所有受试者SOX5基因rs10842262和rs11046966位点的基因型,统计基因型频率并对比各组间差异。结果:健康对照组与COPD组之间(包括COPD合并PH及未合并PH组的全部患者)以及COPD合并PH组与COPD非PH组之间在年龄、性别和吸烟指数上的差别均无统计学显著性。健康对照组与COPD组之间SOX5基因rs10842262位点及rs11046966位点基因型频率分布的差异均存在统计学显著性(P0.05)。COPD合并PH组与COPD非PH组之间SOX5基因rs10842262位点及rs11046966位点各基因型频率分布的差异无统计学显著性。结论:SOX5基因rs10842262和rs11046966位点的基因多态性与COPD的易感性相关,但与COPD相关PH的易感性还不能认为有关联。     

CTLA-4 gene polymorphisms and susceptibility to chronic obstructive pulmonary disease

Objective: The aim of this study was to investigate whether four single nucleotide polymorphisms (SNPs) in CTLA-4 gene are associated with chronic obstructive pulmonary disease (COPD) in a Chinese population. Methods: Samples were collected from a Chinese population and analyzed for the association of SNPs in CTLA-4 gene with COPD in a case-control study. Four SNPs (rs231775, rs3087243, rs231725, rs5742909) in CTLA-4 gene were chosen and genotyped. The results were then analyzed using statistical methods. Results: We found that none of these four SNPs (rs231775, rs3087243, rs231725, rs5742909) in CTLA-4 gene were associated with the disease. Conclusion: Our data suggested that there was no significant association between these four SNPs in CTLA-4 gene and COPD susceptibility in a Chinese population.     

Prediction of exacerbation onset in chronic obstructive pulmonary disease patients

The objective of this study was to develop an algorithm for prediction of exacerbation onset in Chronic Obstructive Pulmonary Disease (COPD) patients based on continuous self-monitoring of physiological parameters from telehome-care monitoring. 151 physiological parameters of COPD patients were monitored on a daily/weekly basis for up to 2 years. Data were segmented in 30-day periods leading up to an exacerbation (exacerbation episode) and starting from a 14-day recovery period post-exacerbation (control episode) and tested in 6 intervals to predict exacerbation onset using k-nearest neighbour (k?=?1, 3, 5). A classifier with sensitivity of 73%, specificity of 74%, positive predictive value of 69%, negative predictive value of 78% and an accuracy of 74% was achieved using data intervals consisting of 5 days. Intelligent processing of physiological recordings have potential for predicting exacerbation onset.     

白细胞介素-10 基因启动子多态性与慢性阻塞性肺疾病易感性的关系

目的　探讨中国汉族人白细胞介素 - 10基因启动子单核苷酸多态性及其与慢性阻塞性肺疾病易感性之间的关系。　方法　应用聚合酶链反应 -限制性片段长度多态性分析方法 ,检测 94名健康吸烟者和 88例吸烟慢性阻塞性肺疾病 (chronic obstructive pulmonary disease,COPD)患者白细胞介素 - 10(interleukin- 10 ,IL- 10 )基因启动子 - 10 82 G/ A、- 819C/ T、- 5 92 C/ A单核苷酸多态性位点基因型。　结果共发现 11种启动子基因型 ,以 AA·TT·AA、AA·TC· AC、AA· TC· AA基因型多见 ;通过对 11种启动子基因型进行分析 ,新发现 ATC、ACA两种单倍型 ;健康吸烟者和吸烟 COPD患者 IL- 10基因启动子- 10 82 G/ A、- 5 92 C/ A位点基因型分布频率差异无显著性 ,- 819C/ T多态性位点与中国汉族人 COPD易感性有关 ;中国汉族人 IL- 10基因启动子等位基因频率与日本人相似 ,与白种人之间差异存在显著性。　结论　中国汉族人 COPD易感性与 IL- 10基因启动子 - 819C/ T位点多态性有关 ;中国汉族人 IL- 10基因启动子至少存在 ATA、ACC、GCC、ATC、ACA5种单倍型。     

结核性胸膜炎合并慢性阻塞性肺疾病患者免疫功能的变化及意义

目的 通过观察T淋巴细胞亚群、B细胞、NK细胞活性来探讨结核性胸膜炎合并慢性阻塞性肺疾病(COPD)患者免疫功能变化.方法 采用流式细胞术分别测定45例结核性胸膜炎合并COPD患者(研究组)、45例COPD患者(COPD对照组)和45例健康体检者(健康对照组)外周血T淋巴细胞亚群、B细胞和NK细胞水平.结果 研究组CD3+、CD4+、CD4+/CD8+、B细胞和NK细胞表达率降低,与健康对照组差异有统计学意义(P ＜0.05);COPD对照组CD3+、CD4+、CD4+/CD8+、B细胞和NK细胞表达率与健康对照组差异有统计学意义(P＜0.05);研究组与COPD对照组的差异无统计学意义.结论 结核性胸膜炎合并COPD患者免疫功能明显低于正常健康人群,增强免疫治疗非常必要.     

Interaction of GSTM1, GSTT1, and GSTP1 Genotypes in Determination of Predisposition to Atopic Dermatitis

The frequency of individual genotypes GSTM1, GSTT1, and GSTP1 and haplotypes was determined in patients with atopic dermatitis and healthy children. The actual frequency of some haplotypes was far below the theoretical value. Some haplotypes were associated with predisposition and resistance to atopic dermatitis.     

Th17细胞与Th1细胞在慢性阻塞性肺疾病炎症发病机制中的调控作用

慢性阻塞性肺疾病(COPD)发病的分子机制目前仍不甚清楚,大量证据表明,T淋巴细胞介导的免疫反应贯穿于COPD的各个阶段,导致炎症反应持续放大.近来研究发现,Th1细胞和Th17细胞均参与了COPD的免疫发病过程,通过相互间作用调控COPD的炎症反应.因此,深入了解COPD炎症发病过程中Th17、Th1细胞免疫应答特征、分化及调控功能,对探讨COPD的致病机制以及免疫调节治疗的靶点具有重要意义.