BACKGROUND & AIMS: Recent genome searches suggest a putative linkage of many loci to susceptibility to type I diabetes. The chromosome 2q31-35 region is reported to be linked to susceptibility to type I diabetes and is thought to contain several diabetes susceptibility loci. These candidate genes include the HOXD gene cluster, BETA2, CTLA4, CD28, IGFBP2, and IGFBP5. Association studies in populations and families are required to confirm and/or identify the actual susceptibility loci. We hereby report several previously unknown DNA polymorphisms for HOXD8, BETA2, and IGFBP5, which we have used along with previously known polymorphisms of HOXD8 and CTLA4 to test whether these candidate loci are the susceptibility genes on chromosome 2q31-35. Using a case-control design with a subsequent family-association approach to confirm associations, we find no evidence that these candidate genes are associated with susceptibility to type I diabetes.

背景与目标： 最近的基因组搜索表明，许多基因座与I型糖尿病易感性之间存在推定的联系。据报道，染色体2q31-35区域与I型糖尿病的易感性有关，并被认为包含多个糖尿病易感性位点。这些候选基因包括HOXD基因簇，BETA2，CTLA4，CD28，IGFBP2和igfbp5。需要在人群和家庭中进行关联研究，以确认和/或确定实际的易感性位点。我们在此报告了HOXD8，BETA2和IGFBP5的几个先前未知的DNA多态性，我们将其与先前已知的HOXD8和CTLA4的多态性一起使用，以测试这些候选基因座是否是染色体2q31-35上的易感基因。使用病例对照设计和随后的家庭关联方法来确认关联，我们没有发现证据表明这些候选基因与I型糖尿病的易感性有关。

BACKGROUND & AIMS: :We conducted a genome-wide association study (GWAS) of anorexia nervosa (AN) using a stringently defined phenotype. Analysis of phenotypic variability led to the identification of a specific genetic risk factor that approached genome-wide significance (rs929626 in EBF1 (Early B-Cell Factor 1); P = 2.04 × 10-7; OR = 0.7; 95% confidence interval (CI) = 0.61-0.8) with independent replication (P = 0.04), suggesting a variant-mediated dysregulation of leptin signaling may play a role in AN. Multiple SNPs in LD with the variant support the nominal association. This demonstrates that although the clinical and etiologic heterogeneity of AN is universally recognized, further careful sub-typing of cases may provide more precise genomic signals. In this study, through a refinement of the phenotype spectrum of AN, we present a replicable GWAS signal that is nominally associated with AN, highlighting a potentially important candidate locus for further investigation.

背景与目标： : 我们使用严格定义的表型对神经性厌食症 (AN) 进行了全基因组关联研究 (gwa)。表型变异性的分析导致鉴定出一种特定的遗传危险因素，该因素具有全基因组意义 (EBF1中的rs929626 (早期b细胞因子1); P   =   2.04  ×   10-7; Or   =   0.7; 95% 置信区间 (CI)  =   0.61-0.8) 与独立复制 (p   =   0.04)，提示一个变异介导的瘦素信号失调可能在AN中起作用。具有变体的LD中的多个snp支持名义上的关联。这表明，尽管AN的临床和病因学异质性已得到普遍认可，但对病例的进一步仔细分类可能会提供更精确的基因组信号。在这项研究中，通过改进AN的表型谱，我们提出了名义上与AN相关的可复制gwa信号，突出了潜在的重要候选基因座，以供进一步研究。

BACKGROUND & AIMS: :Results from pharmacogenetic investigations of methylphenidate (MPH) response in patients with ADHD are still inconsistent, especially among adults. This study investigates the role of genetic variants (SLC6A4, HTR1B, TPH2, DBH, DRD4, COMT, and SNAP25) in the response to MPH in a sample of 164 adults. Genes were chosen owing to previous evidence for an influence in ADHD susceptibility. No significant differences in allele or genotype frequencies between MPH responders and nonresponders were detected. In conclusion, our findings do not support an effect of these genes in the pharmacogenetics of MPH among adults with ADHD.

背景与目标： : 多动症患者中哌醋甲酯 (MPH) 反应的药物遗传学研究结果仍然不一致，尤其是在成年人中。这项研究调查了164名成年人样本中遗传变异 (SLC6A4，HTR1B，TPH2，DBH，DRD4，COMT和SNAP25) 对MPH反应的作用。由于先前的证据对ADHD易感性有影响，因此选择了基因。在MPH应答者和非应答者之间未检测到等位基因或基因型频率的显着差异。总之，我们的发现不支持这些基因在ADHD成人中MPH的药物遗传学中的作用。

BACKGROUND & AIMS: OBJECTIVE:To investigate: (1) the course of coronary heart disease risk factors (lipid profiles and body mass index (BMI)) in the first five years after discharge from inpatient spinal cord injury (SCI) rehabilitation and (2) the association between lifestyle (physical activity, self-care related to fitness, smoking, alcohol, body mass and low-fat diet) and coronary heart disease risk factors during that period. DESIGN:Prospective cohort study. PARTICIPANTS/METHODS:Individuals with SCI (N=130). Total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TG) and BMI were determined at discharge from inpatient rehabilitation and 1 and 5 years after discharge. Using multilevel regression models, the effects of lifestyle (drinking alcohol, smoking, active lifestyle and self-care) on the lipid profiles and BMI were determined. RESULTS:After correction for lesion and personal characteristics, no changes in lipid profiles in the five years after discharge were seen, whereas the BMI increased significantly with 1.8 kg m(-2). A high percentage was at risk of cardiovascular disease due to high BMI (63-75%) or HDL (66-95%). The individuals who indicated to maintain their fitness level as good as possible and the individuals with a low BMI showed better lipid profiles. Individuals with a more active lifestyle showed higher HDL levels. Individuals who avoid smoking showed a 1.5 kg m(-2) higher BMI. CONCLUSION:Lipid profiles seem to stabilize in the years after discharge from inpatient SCI rehabilitation, whereas the BMI increased. Lifestyle factors associated with a favorable lipid profile and BMI could be identified.

背景与目标：

BACKGROUND & AIMS: :Cognitive decline is a feared aspect of growing old. It is a major contributor to lower quality of life and loss of independence in old age. We investigated the genetic contribution to individual differences in nonpathological cognitive ageing in five cohorts of older adults. We undertook a genome-wide association analysis using 549 692 single-nucleotide polymorphisms (SNPs) in 3511 unrelated adults in the Cognitive Ageing Genetics in England and Scotland (CAGES) project. These individuals have detailed longitudinal cognitive data from which phenotypes measuring each individual's cognitive changes were constructed. One SNP--rs2075650, located in TOMM40 (translocase of the outer mitochondrial membrane 40 homolog)--had a genome-wide significant association with cognitive ageing (P=2.5 × 10(-8)). This result was replicated in a meta-analysis of three independent Swedish cohorts (P=2.41 × 10(-6)). An Apolipoprotein E (APOE) haplotype (adjacent to TOMM40), previously associated with cognitive ageing, had a significant effect on cognitive ageing in the CAGES sample (P=2.18 × 10(-8); females, P=1.66 × 10(-11); males, P=0.01). Fine SNP mapping of the TOMM40/APOE region identified both APOE (rs429358; P=3.66 × 10(-11)) and TOMM40 (rs11556505; P=2.45 × 10(-8)) as loci that were associated with cognitive ageing. Imputation and conditional analyses in the discovery and replication cohorts strongly suggest that this effect is due to APOE (rs429358). Functional genomic analysis indicated that SNPs in the TOMM40/APOE region have a functional, regulatory non-protein-coding effect. The APOE region is significantly associated with nonpathological cognitive ageing. The identity and mechanism of one or multiple causal variants remain unclear.

背景与目标： : 认知能力下降是变老的一个令人恐惧的方面。这是导致老年生活质量下降和失去独立性的主要原因。我们调查了五个老年人群对非病理性认知衰老个体差异的遗传贡献。在英格兰和苏格兰的认知老化遗传学 (CAGES) 项目中，我们使用549   692单核苷酸多态性 (snp) 对3511无关的成年人进行了全基因组关联分析。这些个体具有详细的纵向认知数据，从中构建了用于测量每个人的认知变化的表型。位于tom40 (线粒体外膜40同源物的转位酶) 中的一个SNP-rs2075650与认知老化具有全基因组显着关联 (P = 2.5 × 10(-8))。该结果在三个独立的瑞典队列的荟萃分析中被复制 (P = 2.41 × 10(-6))。先前与认知衰老相关的载脂蛋白E (APOE) 单倍型 (与tom40相邻) 对笼子样本中的认知衰老具有显着影响 (P = 2.18 × 10(-8); 女性，P = 1.66 × 10(-11); 男性，P = 0.01)。Tom40/APOE区域的精细SNP图谱将APOE (rs429358; P = 3.66 × 10(-11)) 和tom40 (rs11556505; P = 2.45 × 10(-8)) 识别为与认知衰老相关的基因座。发现和复制队列中的插补和条件分析强烈表明，这种效应是由于APOE引起的 (rs429358)。功能基因组分析表明，tom40/APOE区域的snp具有功能性，调节的非蛋白质编码作用。APOE区域与非病理性认知老化显着相关。一种或多种因果变异的身份和机制仍不清楚。

BACKGROUND & AIMS: :Gender-specific associations between prenatal smoking and birthweight, and neonate intensive health care were studied. Cross-sectional data from 11,583 newborns in the continuous National Health and Nutrition Examination Survey (NHANES) 2003-2008 early childhood data sets were used. Change in infant birthweight and likelihood of receiving neonatal intensive care by prenatal smoking exposure were assessed. Multivariable regression models were used to assess the influence of prenatal smoking on birthweight and likelihood of receiving intensive neonatal health care. Compared with infants from nonsmoking mothers, prenatal smoking associated with significant decrease in infant birthweight, -203.0 g ± 32.5, P < 0.001. The change in birthweight differed between infant boys, -220.2 g ± 44.5, and girls, -184.1 g ± 38.8. Newborns exposed to prenatal smoking were more likely to have low birthweight, odds ratio 1.46, P < 0.03, and to receive neonatal intensive health care, odds ratio 1.20; P < 0.04. It is imperative that prenatal counseling emphasizes prenatal maternal smoking.

背景与目标： : 研究了产前吸烟与出生体重之间的性别特异性关联，以及新生儿重症监护。使用了连续国家健康和营养检查调查 (NHANES) 2003-2008幼儿数据集中的11,583个新生儿的横断面数据。评估了婴儿出生体重的变化以及通过产前吸烟暴露接受新生儿重症监护的可能性。多变量回归模型用于评估产前吸烟对出生体重的影响以及接受重症新生儿保健的可能性。与非吸烟母亲的婴儿相比，产前吸烟与婴儿出生体重显着降低有关，-203.0g ± 32.5，P <0.001。婴儿男孩 (-220.2g ± 44.5) 和女孩 (-184.1g ± 38.8) 的出生体重变化不同。暴露于产前吸烟的新生儿更有可能出生体重低，比值比1.46，P <0.03，并接受新生儿重症监护，比值比1.20; P <0.04。产前咨询必须强调产前母亲吸烟。

BACKGROUND & AIMS: :The objective of the study was to evaluate the association between peripheral venous disease (PVD) and arterial endothelial dysfunction (ED). Arterial and venous diseases have been always considered as two completely different entities, but the recent discovery of a relationship between arterial and venous thrombosis have challenged this assumption. ED, considered to be an early process in the pathophysiology of atherosclerotic disease, could represent a common pathogenetic background. We studied 39 healthy volunteers (median age: 34 years; men: 25.6%). PVD was diagnosed using ultrasound examination, arterial ED using flow-mediated dilation (FMD) and FMD normalized for the peak shear rate (nFMD). Compared with controls, participants with PVD had a lower FMD (15.2 versus 23.4%, P < 0.001) and nFMD (12.7 × 10(-3) versus 19 × 10(-3)/second, P < 0.001). People with the most clinically evident disease had the worst endothelial function. In conclusion, our findings, if confirmed in larger population, might corroborate the idea that venous and arterial disease could have common causes.

背景与目标： : 该研究的目的是评估外周静脉疾病 (PVD) 与动脉内皮功能障碍 (ED) 之间的关系。动脉和静脉疾病一直被认为是两个完全不同的实体，但是最近发现动脉和静脉血栓形成之间的关系对这一假设提出了挑战。ED被认为是动脉粥样硬化疾病病理生理的早期过程，可能代表了共同的发病背景。我们研究了39名健康志愿者 (中位年龄: 34岁; 男性: 25.6%)。使用超声检查诊断PVD，使用血流介导的扩张 (FMD) 进行动脉ED，并针对峰值剪切速率 (nFMD) 标准化FMD。与对照组相比，PVD参与者的FMD (15.2 vs 23.4%，P <0.001) 和nFMD (12.7 × 10(-3) vs 19 × 10(-3)/秒，P <0.001) 较低。临床上最明显的疾病患者的内皮功能最差。总之，如果在更多人群中得到证实，我们的发现可能证实了静脉和动脉疾病可能具有共同原因的观点。

BACKGROUND & AIMS: INTRODUCTION:Mismatch negativity (MMN) is thought to reflect preattentive, automatic auditory processing. Reduced MMN amplitude is among the most robust findings in schizophrenia research. MMN generators have been shown to be located in the temporal and frontal cortices, which are key areas in the pathophysiology of schizophrenia. This study investigated whether frontotemporal cortical thickness was associated with reduced MMN current source density (CSD) strength in patients with schizophrenia. METHODS:Sixteen schizophrenia patients and 18 healthy controls (HCs) were examined using magnetoencephalography while they performed a passive auditory oddball paradigm. All participants underwent a T1 structural magnetic resonance imaging scan in a separate session. We evaluated MMN CSD and cortical thickness, and their associations, in the superior and transverse temporal gyri, as well as in the inferior and middle frontal gyri. RESULTS:Patients exhibited significantly reduced CSD strength in all temporal and frontal areas of interest relative to HCs. There was a positive correlation between CSD strength and cortical thickness in both temporal and frontal areas in HCs. However, schizophrenia patients showed negative correlations between CSD strength and cortical thickness in the bilateral inferior frontal gyri. Additionally, we found positive correlations between frontal cortical thickness and negative and total scores on the Positive and Negative Syndrome Scale (PANSS). CONCLUSIONS:Our findings provide evidence for deficient temporal and frontal MMN generators and a disruption of normal structure-function relationship in patients with schizophrenia.

背景与目标：

BACKGROUND & AIMS: :Tricholoma matsutake, known widely as "matsutake," has great commercial and cultural significance in Japan. Because Japanese production is insufficient to meet the high domestic demand, morphologically similar mushrooms, thought by many to belong to T. magnivelare, are imported from western North America. However, molecular data produced since the early 2000s have indicated that more than one species of matsutake occur in North America and this raises the question of correct naming for the different species. To address this question, we assessed the phylogenetic diversity within North American matsutake based on nuc rDNA ITS1-5.8S-ITS2 (internal transcribed spacer [ITS] barcode) sequences, including newly obtained sequences from the type collections for Agaricus ponderosus and Armillaria arenicola, and morphological characters. Our results agree with earlier indications that three matsutake species occur in North America and allow us to clarify the correct application of names-T. magnivelare from the eastern USA and Canada, T. murrillianum from the western USA and Canada, and T. mesoamericanum from Mexico, newly described here. The existence of the three North American species is further supported by the results of evolutionary divergence analysis, geographical distributions, and morphological characters.

背景与目标： : 松茸，被广泛称为 “松茸”，在日本具有重大的商业和文化意义。由于日本的产量不足以满足国内的高需求，因此从北美西部进口了许多形态相似的蘑菇，这些蘑菇被许多人认为属于T.Magnivelart。然而，自21世纪00年代初以来产生的分子数据表明，北美存在一种以上的松茸，这就提出了为不同物种正确命名的问题。为了解决这个问题，我们根据nuc rDNA ITS1-5.8S-ITS2 (内部转录间隔区 [ITS] 条形码) 序列评估了北美松茸内部的系统发育多样性，包括从黄松茸和arenicola的类型集合中新获得的序列，以及形态特征。我们的结果与先前的迹象一致，即北美有三种松茸物种，这使我们能够阐明名称的正确应用-美国东部和加拿大的T.Magnivelale，美国西部和加拿大的T.Murrilianum以及墨西哥的T. mesoamericanum，在此处新描述。进化差异分析，地理分布和形态特征的结果进一步支持了这三个北美物种的存在。

BACKGROUND & AIMS: :While physical activity (PA) improves functions for activities of daily living, little is known of the association between meeting published PA Guidelines for Americans (PAGA) and meeting published physical function guidelines for maintaining independence. The purpose of this study was to examine the association between meeting the PAGA and meeting independence criteria on the Senior Fitness Tests (SFT). Older adults (N = 265) completed SFTs, assessing cardiorespiratory fitness, lower and upper body strength, mobility, and self-reported aerobic and resistance PA. Chi-square tests and logistic regressions examined associations between meeting PAGA and SFT independence criteria. A significant relationship was found between meeting aerobic PAGA and cardiorespiratory and upper body SFT criteria; a significant relationship was found between meeting resistance PAGA and upper body strength criteria. Although research suggests that PAGA are effective in maintaining fitness in older adults when PA is structured and monitored, mixed results were found for self-reported PA and SFT criteria.

背景与目标： : 虽然身体活动 (PA) 改善了日常生活活动的功能，但人们对满足已发布的美国人PA指南 (PAGA) 与满足已发布的保持独立性的身体功能指南之间的联系知之甚少。这项研究的目的是检查在高级体能测试 (SFT) 中满足PAGA和满足独立性标准之间的关联。老年人 (n   =   265) 完成了SFTs，评估心肺健康，下半身力量，活动能力以及自我报告的有氧和阻力PA。卡方检验和逻辑回归检查了满足PAGA和SFT独立性标准之间的关联。在满足有氧PAGA与心肺和上半身SFT标准之间发现了显着的关系; 在满足阻力PAGA和上半身力量标准之间发现了显着的关系。尽管研究表明，在对PA进行结构化和监测时，PAGA可以有效地维持老年人的健康，但自我报告的PA和SFT标准的结果不一。

BACKGROUND & AIMS: BACKGROUND:Methamphetamine (MAP) is one of the most frequently used illegal substances in Japan, and family and twin studies have suggested that genetic factors contribute to psychostimulant dependence, including MAP dependence. Organic cation transporter 3 (OCT3) has been reported to be involved in the disposition of MAP as well as MAP-induced behavioral changes in animals. Moreover, SLC22A3 (which encodes OCT3) is a candidate gene for MAP dependence because it is located within a chromosomal region associated with substance dependence. METHODS:Using 96 healthy control subjects, linkage disequilibrium (LD) within the SLC22A3 was investigated, and 5 single-nucleotide polymorphisms (SNPs) were selected as haplotype tag SNPs to search for an association with MAP dependence. Single-marker analyses and haplotype analyses of these SNPs were performed in 213 subjects with MAP dependence and 443 healthy controls. RESULTS:SLC22A3 polymorphisms were not significantly associated with MAP dependence in any of the single-marker and haplotype analyses. When subjects with MAP dependence were divided into polysubstance and single-MAP users, genotype and allele frequency of SNP2 (p=0.024, p=0.011, respectively), allele frequency of SNP3 (p=0.037), and haplotypic frequencies for these 2 SNPs (p=0.0438) differed significantly between groups. CONCLUSIONS:These results suggest that polymorphisms of SLC22A3 are related to the development of polysubstance use in Japanese patients with MAP dependence.

背景与目标：

BACKGROUND & AIMS: PURPOSE:Currently, studies on serologic diagnosis of Helicobacter pylori-associated gastric cancer (GC) in Latin America are scarce. The aim of the present study was to evaluate the association between H. pylori serology tests in patients with early precancerous lesions or GC, when compared with non-atrophic gastritis in Colombia, Paraguay, and Mexico, three countries in Latin America with a high prevalence of H. pylori infection but contrasting rates of GC mortality. METHODS:Gastric biopsies and blood samples were obtained from patients attending the gastroenterology or oncology services of hospitals in the three participating countries. IgG antibodies against H. pylori whole-cell antigens and CagA were tested in 1,117 sera using an enzyme-linked immunoabsorbent assay. RESULTS:Positive and significant associations were shown for H. pylori seropositivity and preneoplastic lesions in Mexico (OR 2.0; 95 % CI 1.1-3.4) but not in Colombia (OR 1.2; 95 % CI 0.6-2.1) or Paraguay (OR 1.5; 95 % CI 0.6-3.2); no significant associations were shown for GC in any country. CagA seropositivity was associated with preneoplasic lesions in all three countries (ORs = 2.1, 3.0, and 3.1 for Mexico, Colombia, and Paraguay, respectively), and with GC only in Colombia (OR 4.3; 95 % CI 2.1-9.2). CONCLUSIONS:In countries of Latin America, the IgG CagA test might be a useful biomarker for patients with gastric preneoplastic lesions and for those at risk of developing gastric cancer.

背景与目标：

BACKGROUND & AIMS: :Opioids, such as morphine and fentanyl, are widely used as effective analgesics for the treatment of acute and chronic pain. In addition, the opioid system has a key role in the rewarding effects of morphine, ethanol, cocaine and various other drugs. Although opioid sensitivity is well known to vary widely among individual subjects, several candidate genetic polymorphisms reported so far are not sufficient for fully understanding the wide range of interindividual differences in human opioid sensitivity. By conducting a multistage genome-wide association study (GWAS) in healthy subjects, we found that genetic polymorphisms within a linkage disequilibrium block that spans 2q33.3-2q34 were strongly associated with the requirements for postoperative opioid analgesics after painful cosmetic surgery. The C allele of the best candidate single-nucleotide polymorphism (SNP), rs2952768, was associated with more analgesic requirements, and consistent results were obtained in patients who underwent abdominal surgery. In addition, carriers of the C allele in this SNP exhibited less vulnerability to severe drug dependence in patients with methamphetamine dependence, alcohol dependence, and eating disorders and a lower 'Reward Dependence' score on a personality questionnaire in healthy subjects. Furthermore, the C/C genotype of this SNP was significantly associated with the elevated expression of a neighboring gene, CREB1. These results show that SNPs in this locus are the most potent genetic factors associated with human opioid sensitivity known to date, affecting both the efficacy of opioid analgesics and liability to severe substance dependence. Our findings provide valuable information for the personalized treatment of pain and drug dependence.

背景与目标： : 阿片类药物，如吗啡和芬太尼，被广泛用作治疗急慢性疼痛的有效镇痛药。此外，阿片类药物系统在吗啡，乙醇，可卡因和其他各种药物的奖励作用中起着关键作用。尽管众所周知，阿片类药物的敏感性在各个受试者之间差异很大，但迄今为止报道的几种候选遗传多态性不足以充分理解人类阿片类药物敏感性的广泛个体差异。通过在健康受试者中进行多阶段全基因组关联研究 (gwa)，我们发现跨越2q33.3-2q34的连锁不平衡块中的遗传多态性与痛苦的整容手术后阿片类镇痛药的需求密切相关。最佳候选单核苷酸多态性 (SNP) 的C等位基因rs2952768与更多的镇痛需求相关，并且在接受腹部手术的患者中获得了一致的结果。此外，该SNP中的C等位基因携带者在甲基苯丙胺依赖，酒精依赖和饮食失调的患者中表现出对严重药物依赖的脆弱性较小，并且在健康受试者的人格问卷中 “奖励依赖” 得分较低。此外，该SNP的C/C基因型与邻近基因creb1的表达升高显着相关。这些结果表明，该基因座中的snp是迄今为止已知的与人类阿片类药物敏感性相关的最有效的遗传因素，会影响阿片类镇痛药的功效和对严重物质依赖的责任。我们的发现为疼痛和药物依赖的个性化治疗提供了有价值的信息。

BACKGROUND & AIMS: AIM:To develop a simple and accurate method for quantifying 8-isoprostane in plasma by employing a combination of two-step solid-phase extraction of samples and a commercially available ELISA kit, and by this method to examine the effects of drinking and smoking habits against the levels of plasma 8-isoprostane in healthy Japanese volunteers. METHODS:Plasma 8-isoprostane was extracted with ODS gel suspension followed by NH(2) Sep-Pak column. The 8-isoprostane fractions were assayed using a commercially available ELISA kit. We measured plasma 8-isoprostane levels in 157 healthy Japanese volunteers divided into three groups (64 non-habitual drinkers, 56 moderate drinkers and 37 habitual drinkers) according to their alcohol consumption per week. Genotypes of aldehyde dehydrogenase 2 (ALDH2) were also determined to investigate the plasma 8-isoprostane levels with reference to drinking habits. In addition, the plasma 8-isoprostane levels of 96 non-smokers and 61 smokers from the same subjects were compared. RESULTS:Our method fulfilled all the requirements for use in routine clinical assays with respect to sensitivity, intra- and inter-assay reproducibility, accuracy and dynamic assay range. Significant increases of plasma 8-isoprostane levels were observed in female habitual drinkers when compared with those of non-habitual drinkers (t = 5.494, P<0.0001) as well as moderate drinkers (t = 3.542, P<0.005), and 8-isoprostane levels were also significantly different between ALDH2*2/1 and ALDH2*1/1 in the female habitual drinkers (t = 6.930, P<0.0001), suggesting that excessive drinking of alcohol may increase oxidization stress, especially in females. On the contrary, no significant difference of the plasma 8-isoprostane levels was observed between non-smokers and smokers. CONCLUSION:Our present method was proved to be a simple and accurate tool for measuring plasma 8-isoprostane. However, the clinical utility of plasma 8-isoprostane for drinking and smoking habits was limited since elevated 8-isoprostane levels were observed in female heavy drinkers, and no association was found between smokers and nonsmokers.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:In a large number of studies a positive family history is documented as one of the main risk factors for the development of prostate cancer. In a US population an association between early-onset prostate cancer among familial patients and a more differentiated tumour was shown. The aim of this study was to compare clinical parameters between sporadic and familial or hereditary patients with an age at diagnosis < or =55 years. MATERIAL AND METHODS:The clinical data of prostate cancer patients with an age at diagnosis < or =55 years and who were recruited between July 1999 and the end of June 2004 to the database "familial prostate cancer in Germany" were analysed. The following data were documented for all patients: PSA at diagnosis, histopathological stage, grading, Gleason score and progression-free survival. RESULTS:The clinical data of 685 patients could be completed: 222 (32.4%) had one first-degree relative with prostate cancer, 48 of whom (7.0%) were hereditary; 463 (67.6%) were sporadic. The median age at diagnosis in the hereditary patients was 51.6 (41-55) years, in the familial patients 51.1 (35-55) years and in the sporadic patients 52.0 (38-55) years. The median follow-up was 24 months in hereditary, 36 months in familial and 35 months in sporadic patients. An initial curative therapy with radical prostatectomy or radiotherapy/brachytherapy was planned in 657/685 (95.9%) of the patients. There were no clear differences regarding PSA at diagnosis, the postoperative parameters (organ-confined disease, lymph node involvement, Gleason score, grading) and the progression-free survival in sporadic and familial or hereditary patients. CONCLUSIONS:Patients with an age at diagnosis < or =55 years have a positive family history more often than all prostate cancer patients in Germany. No association could be shown between pathohistological stage or clinical course and a positive family history in patients with an age at diagnosis < or =55 years.

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