单核苷酸多态性与自身免疫性疾病相关性的研究进展

自身免疫性疾病的发生是遗传和环境因素共同作用的结果,在遗传学研究中,HL4基因被认为对自身免疫性疾病的易感性影响最大,而连锁分析发现多个非HLA区域也与自身免疫性疾病的发生相关,而且单核苷酸多态性与疾病的相关性是近年来研究的热点,这不仅为我们进一步了解这类复杂疾病的发病机制提供了线索,而且有可能会有利于发现新的防御及干预措施.本文综述了PTPN22、IL-23R、STAT4、CD226几个热点非HLA基因的单核苷酸多态性与自身免疫性疾病易感性的研究进展.     

沈阳地区汉族人群HLA-DRB1的PCR-SBT分型研究

HLA(humanleukocyteantigen ,HLA)位于人类第 6号染色体短臂 6p2 1.3区域 ,具有高度的遗传多态性 ,作为个体组织细胞的遗传标志物 ,在抗原识别、递呈、免疫应答与调控等方面起着非常重要的作用。其中HLA DR抗原是异基因移植免疫反应中最重要的抗原之一 ,决定其特异性的主要编码基因DRB1座位具有高度多态性 ,DRB1基因分型对器官移植的供体选择、法医学个体认定、HLA与疾病相关性及人类学等研究均具有重要意义。我们用聚合酶链反应 直接测序方法 (PCR SBT)对沈阳地区汉族健康个体进行了DRB1高分辨率的等位基因分析。沈阳地区汉族…     

中国人群CTLA-4基因多态性与系统性红斑狼疮及类风湿性关节炎的相关性研究

系统性红斑狼疮(SLE)与类风湿性关节炎(RA)是常见的自身免疫性疾病,病因未明.研究发现,除了HLA基因的相关性以外,还可能存在其它重要的敏感基因[1].近年来发现CTLA-4基因在自身免疫性疾病发病中的作用,本文检测SLE及RA病人CTLA-4基因多态性,进一步探讨SLE及RA的发病机制.     

脑源性神经营养因子基因与生活事件交互作用对抑郁自杀未遂的影响

目的探讨脑源性神经营养因子(BDNF)基因与生活事件交互作用对于抑郁障碍自杀未遂患者的影响。方法收集伴自杀未遂行为的重性抑郁障碍患者和无自杀未遂的重性抑郁障碍患者各80例,评定汉密尔顿抑郁量表、生活事件量表,采用聚合酶链反应技术(PCR)对BDNF基因多态性进行基因分型,应用MDR软件包分析基因-环境交互作用。结果①与重性抑郁障碍无自杀未遂组相比,重性抑郁障碍自杀未遂组rs6265 AA基因型频率较高,差异具有统计学意义(χ2=7.380,P=0.025);自杀未遂组A等位基因频率较高,差异具有统计学意义(χ2=4.081,P=0.043)。②MDR结果显示,BDNF rs6265基因多态性与负性生活事件存在交互作用模型,该模型的检验样本误差较小(0.4686),交叉验证一致性为10/10,符号检验P0.001。结论 BDNF rs6265基因多态性与负性生活事件之间存在交互作用,该交互作用与重性抑郁障碍自杀未遂行为发生相关。     

弥漫性泛细支气管炎HLA基因的研究进展

弥漫性泛细支气管炎（DPB）是一种两肺弥漫性呼吸性细支气管的气道慢性炎症性疾病。它的发病可能与亚洲黄种人所特有的某些基因有关，参与机体的免疫或变态反应。HLA是机体疾病易感性的主要遗传成分与人体免疫功能相关。目前研究表明，DPB疾病的HLA正相关基因主要为HLA—B5401，HLA＊A11等，负相关基因可能HLA＊B44与HLA—A33和HLA＊DRB1＊1302，而HLA Ⅲ类分子和此病无关，因而认为DPB疾病相关基因位点可能在HLA-B和HLA-A基因之间。     

PTPN22基因多态性与Graves病

弥漫性甲状腺亢进Graves病1是一种多因素引起的疾病,遗传易感性在其发病中起到重要的作用。蛋白酪氨酸磷酸酶非受体型122（protein tyrosine phosphatase non—receptortype22,PTPN22）基因作为其多种自身免疫性疾病的易感基因,被认为通过编码淋巴酪氨酸磷酸酶,在T细胞信号转导中起负性调节作用,可维持免疫系统平衡。而PTPN22的C1858T基因多态性,会使T细胞表面受体的信号减弱和调节性T细胞出现功能缺陷,从而引起Graves病的发生。     

HLA-DQA1和-DQB1等位基因与乙型病毒性肝炎相关性的研究

不同个体对乙型肝炎病毒(Hepatitis B virus, HBV)易感性的差异与个体的免疫特性有关,而后者主要取决于人类主要组织相容性复合体(Major histocompatibility complex, MHC)。人类白细胞抗原(Human leucocyte antigen, HLA)是MHC的基因产物,是首次发现的与疾病有明确关系的遗传系统。HLA复合体作为调节机体免疫应答的重要基因群,与抗HBV免疫反应有着密切的关系,某些特殊的HLA基因型可能影响着HBV感染的慢性化和免疫反应的强弱。作者利用PCR/     

HLA-G与病理妊娠的研究现状

ILA分子由一组被称为组织相容性复合物的基因编码,位于人6号染色体短臂上。具有高度多态性,既不同个体之间多样性。HLA在特异性免疫中处于中心地位。如果一个细胞展示了一种外源的HLA分子,宿主的免疫系统就会破坏它。HLA可分为三大类。HLA-I:受控于A、B、C、E、F、G位点。经典H     

环境与基因对边缘性人格障碍的影响

边缘性人格障碍(BPD)是精神科常见的一种人格障碍,虽然目前对BPD的发病机制尚未完全明了,但已有研究提示基因与环境及两者的交互作用在BPD的发生发展中具有非常重要的作用。本文通过CNKI,MEDLINE和PsysNET等数据库上检索有关边缘性人格与环境、基因之间关系的研究文献,并对文献进行系统总结,发现目前已有较多研究结果支持了基因与环境之间的交互作用在BPD发生发展中的作用。然而,已有关于两者交互作用相关研究尚存在缺陷,需未来的研究进行完善。     

免疫调节基因的多态性与Graves病易感性的相关性研究进展

Graves病(GD)是一种遗传背景强的器官特异性自身免疫性疾病，其核心发病环节是免疫因素，但遗传因素在其发病机制中也起到重要作用。GD的易感基因主要分为免疫调节基因和甲状腺特异性基因，其中免疫调节基因多态性可通过各种机制影响GD的易感性，故可为进一步研究GD的易感基因及发病机制提供新的思路。     

Relationships among alexithymia, adverse childhood experiences, sociodemographic variables, and actual mood disorder: a 2-year clinical follow-up study of patients with major depressive disorder

This 2-year follow-up study examined relationships among alexithymia, adverse childhood experiences, sociodemographic variables, and actual mood disorder among patients with major depressive disorder (N=106). Alexithymia was assessed with the Toronto Alexithymia Scale (TAS-20), depression with the Beck Depression Inventory, and actual mood disorder with the Structured Clinical Interview for DSM-III-R. A questionnaire that assessed sociodemographic characteristics and adverse childhood experiences was also used. Long-lasting alexithymic features were associated with blue-collar work, harsh discipline, unhappiness of the childhood home, depression at 12 months, and major depressive disorder diagnosis at 24 months. Furthermore, the results showed that alexithymic features could also be situational reactions to depression.     

Moderation of adult depression by the serotonin transporter promoter variant (5-HTTLPR), childhood abuse and adult traumatic events in a general population sample

The impact of the promoter polymorphisms of the serotonin transporter (5-HTTLPR) on mood has been studied by two-way interaction models comprising one environmental factor and genotype variants. However, childhood abuse is assumed to be associated with different psychobiological long-term effects than adult traumatic events. Both types of trauma may interact on an individual basis throughout the lifespan moderating the impact of the 5-HTTLPR s allele on depressive disorders. Therefore, the hypothesis of a three-way interaction among the 5-HTTLPR, childhood abuse and adult traumatic experience was tested. Caucasian subjects (1,974) from the general population in Germany (Study of Health in Pomerania (SHIP)) were analyzed. Depressive symptoms were measured with the Beck Depression Inventory (BDI-II). Childhood abuse was assessed with the Childhood Trauma Questionnaire. Adult traumatic events were derived from the SCID interview (DSM-IV) on posttraumatic stress disorder (PTSD). Global three-way interactions among the 5-HTTLPR, adult traumatic experiences and childhood abuse (P?=?0.0007) were found. Carriers of the ss or sl genotypes who had been exposed to childhood abuse and to more than two adult traumatic events had higher mean BDI-II scores (16.0 [95% CI 8.4-23.6]) compared to those carrying the ll genotype (7.6 [4.5-10.7]). These results were supported using a second, more severe definition of childhood abuse (P?=?0.02). No two-way interactions were observed (P?>?0.05). Childhood abuse and adult traumatic events may act synergistically in interaction with the s allele of the 5-HTTLPR to increase the risk for depressive symptoms independently from the lifetime diagnosis of PTSD.     

VULNERABLE TO DEPRESSION

abstract    One notable aspect of femininity is the two-fold higher rate of depression among women. This paper outlines bio-psychosocial models of depression and draws on studies of depressive disorder directly comparing men and women. It is suggested that the finding of consistently higher rates of negative self-evaluation among women may be linked to experiences of parental antipathy and favouritism in childhood, and that there is a continuity of adverse childhood experience between mothers and daughters, but not mothers and sons. It also discusses the implications of the feminine caring role for self-evaluation and affect regulation. The implications for therapeutic practice are outlined.     

Possible roles and determinants of microchimerism in autoimmune and other disorders

Microchimerism is the presence of a low level of non-host stem cells or their progeny in an individual. The most common source of microchimerism is pregnancy. During pregnancy, bi-directional trafficking of hematopoietic cells occurs through the placenta and these microchimeric cells persist for decades after childbirth. A possible role of microchimerism in the pathogenesis of some (systemic sclerosis, systemic lupus erythematosus, primary biliary cirrhosis, autoimmune thyroid diseases and juvenile myositis) but not all autoimmune diseases has been suggested by recent studies. Contradictory reports exist regarding HLA allelic associations with persistent T lymphocyte microchimerism. Although much of the focus of past studies has been on microchimerism in the effector arm of the immune system, increasing evidence suggests that microchimeric cells may differentiate into many lineages in different tissues raising additional possible roles for these cells. The possibility of microchimerism in many organs should induce an exploration of how persistent mixtures of cells of different genetic backgrounds throughout the body may influence diverse physiologic processes during life. In the present review, we discuss possible influencing factors and roles of all forms of microchimerism in autoimmune and non-autoimmune diseases. A better understanding of the immune mechanisms, along with the identification of environmental and genetic risk factors, is crucial for further deciphering the many possible implications of maternal-fetal and fetal-maternal cell trafficking in health and disease.     

Recognition of childhood depression: personal reminiscences

Prior to 1970, childhood depression was not considered a valid clinical entity by American psychiatrists. One of the early clues was provided in the 1950s by the author's observation of depressive symptoms in children and young adolescents with undescended testicles. This finding was extended to children with several chronic diseases, many of whom exhibited depressive symptoms as well. Eventually, depressive symptomatology was found in children without any physical disorders. This was followed by the introduction of a diagnostic instrument, called the Children's Affective Rating Scale (CARS), later converted into a more formal system called the Child Assessment Schedule (CAS). A provisional classification of childhood depression was published in 1972. Our examination of children with depressive disorders has revealed several modes of family interaction, of which the most important were: separation from important love objects; depreciation and rejection; and affective disorders in parents. Several children with bipolar disorder stimulated our interest in this disorder and led to a pilot study of children of bipolar, lithium-responding parents. Some of these children with bipolar illness had a clear-cut response to lithium and were strong augmenters of the average evoked potentials (EPs). Next, our group investigated the urinary excretion of norepinephrine and its metabolites in chronically depressed children who differed from a normal control group. The foregoing studies, along with major contributions by other child psychiatrists, eventually led to the acceptance of childhood depression as a clinical entity in US psychiatry. The acceptance of juvenile bipolar disorder had to await further research by a new generation of child and adult psychiatrists.     

The increasing incidence and prevalence of female multiple sclerosis--a critical analysis of potential environmental factors

Multiple sclerosis (MS) is the most common acquired inflammatory demyelinating disorder of the central nervous system (CNS). Not unlike many inflammatory diseases with a presumed autoimmune pathogenesis, it has been established that there is a female preponderance in prevalence. While in the past it was shown that there are two women for every man with a diagnosis of MS, recent serial cross-sectional assessments provide compelling evidence for an increase of the female to male sex ratio in patients with relapsing-remitting MS over the last decades. An understanding of this phenomenon might provide key insights into the pathogenesis of the disease but also may have implications for health-care strategies and further research efforts. We review possible etiologies for the gender disparity in MS, and we discuss possible underlying causes. We determined that the biologically most plausible explanations for a disproportional increase of MS among women in some population may be the role of vitamin D in MS pathogenesis. Decreased sun exposure may be a critical factor in diminished vitamin D levels in many recent cohort studies. Vitamin D insufficiency or deficiency has been shown to affect T cell differentiation and regulation, which may affect cellular immune responses against autoantigens and pathogens that have been associated with the etiology of MS. Vitamin D also appears to impact B cell activation and differentiation, another cell type that has been implicated in the inflammatory cascade underlying CNS autoimmune disease.     

Definitions and distinctions among depressive syndromes and symptoms: implications for a better understanding of the depression-cardiovascular disease association

OBJECTIVES: A prognostic role for depressive disorder presence and/or elevated depressive symptoms in the onset and recurrence of cardiovascular disease has been largely supported. Depression is a multifaceted disorder, encompassing a wide range of somatic, cognitive, and mood symptoms; it varies in intensity, duration, frequency, course, and family history; it can be assessed continuously or categorically; it can be obtained by interview or by self-report; and importantly, the cardiac prognostic impact of these distinctions may vary. We provide an overview of definitions and possible assessment of depression, and we discuss key assessment distinctions. CONCLUSION: Examining the predictive ability of these key distinctions of depression for acute coronary syndrome recurrence would be of benefit to future research in this field.     

Depression and situational helplessness/mastery in a sample selected to study childhood parental loss

This paper continues the investigation of differential states of depression in a sample of 225 women selected for different experiences of parental loss in childhood by introducing a measure of the cognitive-behavioural set of situational helplessness/mastery which uses actual rather than hypothetical situations as the basis for scoring. The measure is also specifically designed to take account of differences according to the time of its completion (before, during or after a psychiatric episode). The relationship is explored between this attribute and, on the one hand, depressive disorder, and on the other, parental loss in childhood. Rates of current depression increased progressively with the degree of helplessness rated not only for the current period but also, in instances where there was a current depressive episode, for the time immediately prior to its onset. For those with depression the degree of helplessness was often found to be higher during the episode than just before it. A measure of helplessness in childhood was associated not only with current depression but with previous episodes. Continuity between childhood and adult helplessness was apparently considerable, and both were associated with loss of mother in childhood. A rating of helplessness shown in the past just before onset of a prior depressive episode suggested a similar raised rate compared to those never depressed. The failure to find an association between prior episodes of depression and current helplessness among those currently not depressed is discussed in terms of the likely durability of long-term cognitive-behavioural sets and the possibility that with improved social circumstances and relationships, helplessness may decrease.(ABSTRACT TRUNCATED AT 250 WORDS)     

Immunogenetics of ageing

The ageing process is very complex. Human longevity is a multifactorial trait which is determined by genetic and environmental factors. Twin and family studies imply that up to 25% of human lifespan is heritable. The longevity gene candidates have generally fallen into the following categories: inflammatory and immune-related factors, stress response elements, mediators of glucose and lipid metabolism, components of DNA repair and cellular proliferation and mitochondrial DNA haplogroups. Because of the central role of HLA molecules in the development of protective immunity and the extraordinary degree of polymorphism of HLA genes, many studies have addressed the possible impact of these genes on human longevity. Most of the data available so far demonstrated a possible role of HLA class II specificities in human longevity but definitive evidence has remained elusive. Although the data are limited and controversial, it has been hypothesized that longevity could be associated with cytokine gene polymorphisms correlating with different levels of cytokine production, thereby modulating immune responses in health and disease. Because of the essential role of cytokines in immune responses, the regulation of cytokine gene expression and their polymorphic nature, the genetic variations of these loci with functional significance could be appropriate immunogenetic candidate markers implicated in the mechanism of successful ageing and longevity. In addition, several other genes such as Toll-like receptor genes, Cycloxygenases (COX)/Lipoxygenases (LOX), CCR5, NK receptor genes and MBL2 have been assessed as a possible biomarkers associated with ageing. This review will summarize the data on the role of these immune genes in human longevity.     

Early childhood adversity and adolescent depression: the mediating role of continued stress

BACKGROUND: While various conceptualizations of the link between childhood adversity and later depression have been offered, most have not accounted for the possibility that early adversity predicts continuing stress proximal to depression onset. Thus, the present study tested the possible mediating role of recent stress in the association between early adversity and depression in late adolescence.METHOD: Study questions were examined in a longitudinal community sample of 705 youth who were contemporaneously assessed for early adversity exposure prior to age 5 years, chronic and episodic stress at age 15 years, and major depression prior to age 15 years and between 15 and 20 years. RESULTS: Total youth stress burden at age 15 years mediated the effect of early adversity on depression between ages 15 and 20 years, and none of the observed relationships were moderated by onset of depression prior to age 15 years. CONCLUSIONS: These findings suggest that continued stress exposure proximal to depression onset largely accounts for the association between early adversity and depression in late adolescence. Intervention should thus focus on disrupting the continuity of stressful conditions across childhood and adolescence. Future studies of the neurobiological and psychosocial mechanisms of the link between early experiences and depression should explore whether the effects of early experiences are independent of continuing adversity proximal to depressive onset.