雄激素性脱发相关研究进展

雄激素性脱发亦称男性型脱发,主要以毛发渐进性缺失为表现形式.研究显示雄激素性脱发是一种雄激素依赖的,可能受多种基因与环境因素共同影响的多因子疾病.尽管病理生理过程有遗传因素的参与,但其结论没有完全揭示,主要研究进展即雄激素及其代谢产物的作用机制.同时,一些遗传易感基因或基因座证实与此病的发展有关.本文将这些与雄激素性脱发相关的致病因素进行综述.     

家族性乳腺癌遗传易感基因研究现状

家族性乳腺癌与遗传易感基因的突变有密切的联系 ,目前已发现多种乳腺癌遗传易感基因 ,它们分别定位于 17号和 13号染色体的长臂和 8号染色体的短臂上。乳腺癌家族中易感基因突变携带者患乳腺癌的危险性明显高于普通人群 ,具有不同易感基因突变的乳腺癌患者其组织学特征也有所不同。本文就家族性乳腺癌遗传易感基因的研究进展作一综述     

家族性乳腺癌遗传易感基因研究现状

家族性乳腺癌与遗传易感基因的突变有密切的联系，目前已发现多种乳腺癌遗传易感基因，它们分别定位于１７号和１３号染色体的长臂和８号染色体的短臂上。乳腺癌家族中易感基因突变携带患乳腺癌的危险性明显高于普通人群，具有不同易感基因突变的乳腺癌患其组织学特征也有所不同。本就家族性乳腺癌遗传易感基因的研究进展作一综述。     

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。     

Ⅰ型糖尿病的分子遗传研究进展

Ⅰ型糖尿病是一种多基因遗传病 ,涉及的遗传因素十分复杂。近年来 ,对 型糖尿病易感位点或相关基因的鉴别进展迅速 ,已报道了十余个 型糖尿病易感位点或相关基因。本文对 型糖尿病易感位点或相关基因的研究情况作一综述     

糖尿病肾病遗传学研究进展

遗传因素在糖尿病肾病(DN)的发生发展中起重要作用。DN属于多基因病,其遗传易感模式有主基因效应、等效基因效应和多基因效应模式。目前寻找DN易感基因的策略多采用家系基础上的传递不平衡检测(TDT)和群体病例-对照的遗传关联研究。已发现多个基因的多个位点与DN有相关关系,但是在不同人群中有不同的结论。     

环境基因组学和环境基因组计划

环境基因组 (ＥｎｖｉｒｏｎｍｅｎｔａｌＧｅｎｏｍｉｃｓ)和环境基因组计划 (ＥｎｖｉｒｏｎｍｅｎｔａｌＧａｎｏｍｉｃｓＰｒｏｊｅｃｔ,ＥＧＰ)是在人类基因组 (ＨＧＰ)基础上发展的功能基因组内容之一 .人类疾病的发生发展与环境因素及环境因素相关疾病的遗传敏感性有关 .通过环境基因组研究可寻找到环境因素的易敏感基因 ,在遗传和物理图谱的建立和测序基础可发现和分离出大批新基因 .环境基因组计划 (ＥＧＰ)是研究与环境因素相关疾病的遗传敏感性 ,寻找对环境因素损伤易感的基因 .区别易感人群 ,研究易感性基因产物及其对环境暴露…     

精神分裂症易感基因

精神分裂症是一类遗传倾向性较高的多基因疾病.近年来,随着遗传学和分子生物学为主的多学科研究技术的快速发展,不断有新的易感基因报道;一些重要易感基因的生物学功能及其在该疾病发病机制中的作用研究也取得了一定进展.     

糖尿病肾病遗传学研究进展

遗传因素在糖尿病肾病(DN)的发生发展中起重要作用。DN属于多基因病，其遗传易感模式有主基因效应、等效基因效应和多基因效应模式。目前寻找DN易感基因的策略多采用家系基础上的传递不平衡检测(TDT)和群体病例-对照的遗传关联研究。已发现多个基因的多个位点与DN有相关关系，但是在不同人群中有不同的结论。     

Ⅰ型糖尿病的分子遗传研究进展

Ⅰ型糖尿病是一种多基因遗传病，涉及的遗传因素十分复杂，近年来，对Ⅰ型糖尿病易感位点或相关基因的鉴别进展迅速，已报道了十余个Ⅰ型糖尿病易感位点或相关基因。本对Ⅰ型糖尿病易感位点及相关基因的研究情况作一综述。     

Potential Involvement of the Stem Cell Factor Receptor c-kit in Alopecia Areata and Androgenetic Alopecia: Histopathological,Immunohistochemical, and Semiquantitative Investigations

Alopecia areata (AAR) and androgenetic alopecia (AGA) are two major forms of alopecia based on altered hair growth condition. In general, the cell cycle is regulated by several mechanisms including the stem cell factor/c-kit signaling. To assess a role for stem cell activity in alopecia, we performed histopathological, immunohistochemical, and semiquantitative analyses of c-kit as well as Ki-67 in scalp biopsy specimens obtained from 14 patients with AAR, 18 patients with AGA, and 6 age-matched control subjects, using the specific antibodies. Formalin-fixed, paraffin-embedded skin sections were examined. Immunoreactivities for Ki-67 and c-kit were localized in keratinocytes and melanocytes in the outermost layer of hair follicles. The mean length of hair follicles was significantly shorter in the AAR and AGA groups than in the control group. The mean number of Ki-67-immunoreactive cells per follicle was significantly reduced in the AAR and AGA groups as compared with the control group. The mean number of c-kit-immunoreactive cells per follicle was significantly increased in the AAR and AGA groups as compared with the control group. Our results indicate that c-kit is upregulated in the hair follicle cells in these forms of alopecia, and suggest that the upregulation reflects a negative feedback mechanism in response to possible downregulation of the ligand stem cell factor.     

Big head? Bald head! Skull expansion: alternative model for the primary mechanism of AGA

Currently, the predominant hypothesis explains androgenetic alopecia (AGA) as a process reliant upon affected follicles being individually programmed to accumulate dihydrotestosterone (DHT), which then causes progressive follicular miniaturisation. The goal of this paper is to suggest that such miniaturisation may result from an exaggeration of the bone remodelling process causing a reduction in blood supply to the capillary network within the affected region. The bones of the human skull continue to grow during adulthood and observations made of those with AGA suggest that such growth may be responsible for the development of this condition. Studies of human cranial anatomy indicate that frontal and parietal bone growth can account for the development of the male pattern baldness (MPB) profile and the variations that can occur in the rate and location of hair loss. Steroid hormones such as DHT promote facial and body hair growth. Logically, this suggests that DHT should stimulate hair growth within the MPB region and not hair loss. However, DHT also has an anabolic effect on bone formation, and it is hypothesised that this stimulation of bone growth will overwhelm the hair growth promoting effects of DHT. Androgen receptor sites, 5-alpha-reductase (5alpha-R) and DHT have all been associated with AGA, but they also exist within numerous types of bone cells. DHT will stimulate the proliferation of osteoblast cells and the formation of new bone. Verification of this hypothesis would imply that DHT is primarily involved with AGA through its stimulation of the skull expansion process rather than through interaction with individual follicles. Also, increased androgen receptor gene expression, 5alpha-R activity and subsequent production of DHT within the MPB region of balding individuals, may simply represent the body's attempt to compensate for the skull expansion expression of hair follicle miniaturisation. Furthermore, it suggests that MPB region follicles are not individually programmed for hair loss. A redirection of genetic research towards the identification of those genes responsible for skull shape and development would be appropriate, and may reveal the genetic connection to AGA including its paternal link.     

雄激素性秃发的诊疗现状

雄激素性秃发 (Androgenetic Alopecia,AGA) 是一种十分常见的毛发疾病,在男性和女性中均可发生。AGA 的主要临床表现为毛发微型化、稀疏、发际线上移,但在男女性中症状有所不同。AGA对个人形象的影响及其治疗效果欠佳的现状,导致患者的日常生活及心理状态都会受到消极影响。本文主要从AGA的发病机制、诊断、治疗、目前面临的挑战及展望等方面对该病进行简述,为探索其诊疗方法提供思路。     

Ketocazole as an adjunct to finasteride in the treatment of androgenetic alopecia in men

Dihydrotestosterone (DHT) binding to androgen receptors (AR) in hair follicles is commonly accepted as the first step leading to the miniaturizing of follicles associated with androgenetic alopecia (AGA). Testosterone is converted to DHT by the enzyme 5alpha-reductase. Finasateride a 5alpha-reducase inhibitor blocks the production of DHT and is currently used to treat AGA. The inhibition is not complete but a reduction of DHT systemically and in the scalp is accomplished. Ketoconazole has been clinically shown to be effective in the treatment of AGA. In this paper, evidence is presented to support the hypothesis that ketoconazole 2% shampoo has a local disruption of the DHT pathway. It is proposed that using ketoconazole 2% shampoo as an adjunct to finasteride treatment could lead to a more complete inhibition of DHT and thus better treat AGA.     

Prostaglandin D2 inhibits hair growth and is elevated in bald scalp of men with androgenetic alopecia

Testosterone is necessary for the development of male pattern baldness, known as androgenetic alopecia (AGA); yet, the mechanisms for decreased hair growth in this disorder are unclear. We show that prostaglandin D(2) synthase (PTGDS) is elevated at the mRNA and protein levels in bald scalp compared to haired scalp of men with AGA. The product of PTGDS enzyme activity, prostaglandin D(2) (PGD(2)), is similarly elevated in bald scalp. During normal follicle cycling in mice, Ptgds and PGD(2) levels increase immediately preceding the regression phase, suggesting an inhibitory effect on hair growth. We show that PGD(2) inhibits hair growth in explanted human hair follicles and when applied topically to mice. Hair growth inhibition requires the PGD(2) receptor G protein (heterotrimeric guanine nucleotide)-coupled receptor 44 (GPR44), but not the PGD(2) receptor 1 (PTGDR). Furthermore, we find that a transgenic mouse, K14-Ptgs2, which targets prostaglandin-endoperoxide synthase 2 expression to the skin, demonstrates elevated levels of PGD(2) in the skin and develops alopecia, follicular miniaturization, and sebaceous gland hyperplasia, which are all hallmarks of human AGA. These results define PGD(2) as an inhibitor of hair growth in AGA and suggest the PGD(2)-GPR44 pathway as a potential target for treatment.     

An investigation of apoptosis in androgenetic alopecia

While the androgens, including dihydrotestosterone (DHT), have been implicated in the development of androgenetic alopecia (AGA), the exact mechanism by which they exert their effect(s) is unknown. Since apoptosis is an integral component of the normal cycling of human hair, we investigated individuals clinically affected by AGA to assess whether objective differences in the expression of apoptosis-related immunohistochemical markers could be observed in scalp biopsies. Specimens from 16 alopecic male patients were stained with bd-2 and the terminal deoxynucleotidyltransferase dUTP fluorescein nick end-labeling (TUNEL) method was used to assess apoptotic activity in affected and unaffected areas ofthe scalp. Immunoreactivity was analyzed by quantifying staining differences within the same individual. Sections from 3 human volunteers were used to establish the method validity. Significant differences in the bcl-2 staining index (0.67 versus 0.42, p < 0.05) and TUNEL expression (5.7 versus 10.2, p < 0.05) were observed between the areas of the scalp that were clinically affected (frontal) and unaffected (occipital) by AGA. The Gaussian distributions of bcl-2 and TUNEL staining suggest that a relatively uniform population of follicles exists at the frontal hairline and/or that synchrony of follicular cycling occurs in AGA. The apoptosis "hot spot" revealed by TUNEL staining in the bulge-isthmus region of the murine follicle is also identifiable in the human follicle.     

Prevalence of NIDDM in Mexicans with paraphyletic and polyphyletic surnames

It has been hypothesized that the greater prevalence of non-insulin-dependent diabetes mellitus (NIDDM) in Mexicans may be related to their greater degree of Amerindian genetic admixture (AGA). The aim of this unmatched case–control study was to correlate the prevalence of NIDDM with AGA in 10 Mexican Mestizo populations non-randomly selected by surname. A sample of 1,699 unrelated persons, >44 years and residing in the state of Nuevo León, was selected on the basis of paraphyletic or polyphyletic surnames and interviewed in the Instituto Mexicano del Seguro Social (IMSS). All subjects received a medical examination, and diabetes was diagnosed on the basis of World Health Organization criteria. Three genetic marker systems were analyzed, and the percentage of AGA was calculated. Logistic regression analysis was performed with the prevalence as the dependent variable and sex and surname as the independent variables. The Spearman rank–order correlation analysis was calculated between the age-adjusted prevalence (45–75+ years) and AGA. The correlation revealed a pattern of increasing prevalence of NIDDM with increasing Amerindian ancestry by surname. Am. J. Hum. Biol. 12:721–728, 2000. © 2000 Wiley-Liss, Inc.     

Energy minimum theorem based on AGA, Lyapunov and force field for CADD techniques

This paper employs the energy minimum to enhance drug docking efficiency in a computer aided drug design (CADD) system. The energy minimum application is used to enhance CADD docking performance. The proposed method is discussed in three aspects, adaptive genetic algorithms (AGA), Lyapunov stability theorem and molecular force field. As in previous researches, docking is the crucial component in drug development. The number of docking sites affects the drug docking speed. Reducing the scope of the geometric search is the key task. This paper proposes AGA to improve geometric molecular docking search efficiency. The Lyapunov stability theorem forwards the stability state identification. Protein folding intention generally finds the most appropriate stability state when the thermodynamic and molecular mechanical free energy has reached the lowest point. The AMBER force field simulation is used to discover the molecular statistical mechanics in a drug-ligand. AGA was found better in terms of processing the geometric graphic search operation. The AGA and Lyapunov algorithms were utilized to sieve out the global energy minimum approach from the numerous, raw docking sites.     

Adams-Oliver syndrome: clinical description of a four-generation family and exclusion of five candidate genes

We present a Belgian Adams-Oliver syndrome (AOS) family with 10 affected individuals over four generations, of which six were available for this study. Clinical symptoms observed in these patients were very variable as previously reported in other families and included large areas of alopecia on the vertex of the skull and serious limb reduction defects with agenesis of all toes of one foot. To identify the disease-causing gene, we sequenced the MSX1, CART1, P63 (P73L), RUNX2, and HOXD13 genes in this family and nine previously reported families, but no disease-causing mutations were found. Further investigation is ongoing in these families in order to identify the genetic cause of AOS.