MMP9和MMP20基因多态性与老年性黄斑变性风险的相关性分析

目的研究基质金属蛋白酶9(MMP9)和MMP20基因多态性与老年性黄斑变性(AMD)风险的相关性。方法选择2015年9月-2017年9月内江市第一人民医院眼科收治的AMD患者和体检健康人群各150例,收集血样。采用Sequenom MassARRAY SNP基因分型技术对MMP9和MMP20基因上rs17576、rs3787268、rs2274755和rs10895322四个SNP进行分型。结果 AMD组和对照组间性别、年龄、BMI、糖尿病、血脂异常、甲状腺功能异常及吸烟情况的差异均无统计学意义(P0.05)。四个SNP均符合Hardy-Weinberg平衡定律(P-HWE0.05)。AMD组中rs17576、rs3787268和rs2274755的最小等位基因频率均显著高于对照组;而rs10895322的最小等位基因频率显著低于对照组(P 0. 05)。AMD组rs17576位点的AG和GG基因型频率、rs3787268位点的GA和AA基因型频率、rs2274755位点的GT和TT基因型频率均显著高于对照组;而rs10895322位点的AG和GG基因型频率显著低于对照组(P0.05)。此外,rs17576和rs2274755在三个遗传模型下均与增高AMD风险具有相关性; rs3787268位点在隐性和加性模型下与增高AMD风险具有相关性;而rs10895322位点在隐性和加性模型下与降低AMD风险具有相关性(P0.05)。结论 MMP9基因上rs17576、rs3787268和rs2274755位点可能与增加AMD风险相关,而MMP20基因上rs10895322位点可能与降低AMD风险相关。     

老年黄斑变性可选中医治疗

老王今年52岁，以前双眼视力一直很好，可是近两年感觉看东西有点模糊，曾经参加体检，医生说有轻微的白内障，既然轻微，老王也就没在意，直到这两天左眼前突然出现一个固定的黑影，看东西变形，才到中国中医科学院眼科医院检查，结果发现左眼眼底出血，长了新生血管，右眼眼底也有了萎缩表现，诊断为“老年性黄斑变性”。大夫说这个病不容易治，进展的话会导致严重的视力障碍。老王很想弄明白，这“老年性黄斑变性”到底是怎么回事呢？真有这么严重吗？[编者按]     

老年黄斑变性 影响视力

<正>随着人口老龄化,到医院眼科就诊的老年性黄斑变性病人也多起来了,该病视力损伤大,缺少有效的治疗手段,咨询该病的人比较多。老年性黄斑变性也称为年龄相关性黄斑变性,是中心视力下降的致盲性眼底退行性病变。该病发病率与年龄增长呈正相关,目前已成为50岁及以上人群重度视力     

补体因子H与ARMS2基因多态性与年龄相关性黄斑变性的关联研究

目的 探讨补体因子H (complement factor H,CFH)基因Y402H和年龄相关性黄斑变性易感基因2(age-related maculopathy susceptibility 2,ARMS2) A69S多态性与年龄相关性黄斑变性(age-related macular degenera-tion,AMD)的关联,并分析Y402H和A69S与环境因素之间的交互作用.方法 采用以医院为基础的多中心病例对照研究,共纳入病例545人,对照480人,使用统一的调查问卷收集人口学资料和环境因素,并进行体格检查和眼科检查,纳入成功鉴定基因型的病例535人,对照469人,应用Logistic回归进行多因素分析,并计算交互作用超额危险度(relative excess risk of interaction,RERI)、交互作用归因比(attributable proportion of interaction,API)及交互作用指数S(interaction index S,Index S).结果 Y402H和A69S均与AMD有相关性,在对可能的混杂因素进行调整后,吸烟与Y402H的RERI、API及Index S分别为0.919、28.210％、2.433,吸烟与A69S的RERI、API和Index S分别为0.869、24.438％、2.108.结论 CFH Y402H和ARMS2 A69S基因多态性均与AMD相关,但Y402H突变率低,Y402H和A69S均与吸烟在AMD的发生中存在交互作用.     

中药和食疗可防治老年黄斑变性

老年性黄斑变性是一种中老年人的黄斑部进行性变性疾病。是中老年人中的常见眼底疾病。黄斑变性是65岁以上的老年人影响和丧失视力的主要原因之一。黄斑是位于视网膜后面低度敏感的组织薄膜,当感光细胞发生病变出现退化,就会长出脆弱的新血管,这些血管一旦发生渗血,便可迅速使人丧失中央视力。研究表明该病的发生与衰老、脉络膜血管硬化等多种因素有关。这种病至今尚缺乏安全而特别有效的治疗方法。     

年龄相关性黄斑变性的治疗现状

老年黄斑变性（age2related macular degenerati称AMD或ARMD）又称年龄相关性黄斑变性,常伴有进行性视力损害,严重影响老年人的生存质量,是全世界第三位不可逆性和西方国家老年人首位的致盲眼病,其在亚洲发病率亦呈逐渐增多的趋势。     

叶黄素——老年黄斑变性的救星

老年黄斑变性义称“年龄相关性黄斑变性”,大多发生予45岁以上的人群。随着生活质量的提高,老年性眼病,特别是老年性眼底病变越来越受到社会的重视,其患病率随年龄增长而增高,是当前老年人致盲的重要疾病之一。下面谈谈老年黄斑变性的一些相关知识,以便大家更好地了解它,战胜它。     

老年黄斑变性的相关研究进展（综述）

回顾了近年来老年黄斑变性（aging macular degeneration,AMD）的病因、发病机制、治疗及预防方面的研究新进展。有关危险因素新的流行病学调查结果为防治提供了理论依据,视杆细胞易感性学说提出了新的发病机制,新的治疗方法如抗血管内皮生长因子药物的应用,光动力治疗、局限性黄斑转位术、经瞳孔温热治疗及基因治疗都有一定的效果。带来了新的希望,但同时也存在许多问题,需要继续探讨。     

IL-6基因单核苷酸多态性与系统性红斑狼疮的相关性研究

目的探讨白细胞介素（interleukin,IL）6单核苷酸多态性（single nucleotide polymorphism,SNP）（rs1800796）与系统性红斑狼疮（systemic lupus erythematosus,SLE）的易感性。方法选取SLE患者666例作为病例组,年龄、性别匹配的569例正常人作为对照组,采用TaqMan基因分型技术检测rs1800796基因型频率。结果 Rs1800796 SNP的基因型（CC,CG和GG）频率和等位基因（C和G）频率在SLE患者和对照间差异均无统计学意义（均有P>0.05）。Rs1800796与SLE临床表现的关联性分析发现,C等位基因频率在伴有浆膜炎的SLE患者中低于不伴有浆膜炎的SLE患者（P=0.019）。但C等位基因频率的分布在是否表现有颧部红斑、盘状红斑、光敏感、口腔溃疡、关节炎及狼疮肾炎的SLE病人间差异均无统计学意义（均有P>0.05）。结论尚未发现IL-6rs1800796在中国汉族人群与SLE遗传易感性有关。Rs1800796 C等位基因可能对SLE病人并发浆膜炎起保护作用。     

SMAD7基因单核苷酸多态性与散发性胃癌、肠癌发病风险相关性研究

目的 探讨SMA D7基因上位点rs8085824多态性与胃癌、肠癌易感性的关系.方法 利用Sequenom系统对来自上海汉族人群的250例胃癌患者,229例肠癌患者及303例健康对照组进行位点rs8085824检测,并利用非条件Logistic回归对检测结果进行相关统计.结果 rs8085824位点多态性在胃癌病例对照组显性遗传模型中有显著性差异,携带等位基因T的CT-TT基因型与CC基因型相比较,OR值为2.564(95％ CI:1.152～5.704,P=0.021),rs8085824位点多态性分布在肠癌组中没有出现显著性差异.结论 SMAD7基因的位点rs8085824多态性位点与胃癌发病风险相关并符合显性遗传模型,与肠癌发病风险无相关性.     

Quality of life in age-related macular degeneration: a review of available vision-specific psychometric tools

Purpose Age-related macular degeneration (AMD) has a considerable impact on older adults’ independence and autonomy. Recently, patient reported outcomes (PROs) such as QoL have been met with increasing interest by the scientific community, healthcare payers and planners. Against this background, the multitude of psychometric tools used to measure QoL in AMD was reviewed. Methods A search of the literature from 1990 onwards yielded 355 results, out of which 58 publications were included in the review. Data regarding design, validation and extent of utilization were obtained where available. Results The National Eye Institute–Visual Function Questionnaire (NEI VFQ-25-item) was found to be the most often used (29% of studies) and best validated psychometric tool, followed by the Visual Function Questionnaire (VF-14; 17%), and the Impact of Vision Impairment Profile (IVI; 9%). Most tools that were identified have been validated for the use in AMD patients. Conclusion Psychometric tools specifically designed to measure vision-related quality of life are well equipped and validated to measure QoL in AMD. More recent developments such as the Macular Disease-dependent Quality of Life (MacDQoL) questionnaire might be able to depict dimensions of vision-related QoL in greater depth. Future studies should endeavour to use a suggested standard when gathering data on vision related QoL, allowing for international comparisons.     

叶黄素对老年性黄斑变性预防及治疗作用的Meta分析

目的评价叶黄素对老年性黄斑变性（AMD）的预防及治疗作用。方法采用电子检索、手工检索及索引检索方式检索所有叶黄素对AMD预防及治疗作用的病例对照研究、队列研究的中英文研究文献,对纳入文献进行质量评价后提取数据信息,采用专用软件RevMan4．2完成系统评价过程。结果共纳入9篇临床研究,合并OR为0．81（0．71,0．92）。结论叶黄素可以在一定程度上预防AMD的发生或延缓其发展。     

血清叶黄素水平与老年性黄斑变性关系的Meta分析

目的系统评价老年性黄斑变性(age-related macular degeneration,AMD)患者血清叶黄素水平与对照组相比差异有无统计学意义。方法以电子检索结合手工检索及索引检索的方式检索中外数据库中对AMD患者及其对照组进行血清叶黄素水平测定的病例对照研究、队列研究的中英文研究文献,按照纳入及排除标准从中选择符合标准的8篇文献,提取其数据信息,采用专用软件RevMan 5.0完成系统评价过程。结果共纳入8篇临床研究,固定效应模型合并的标准化均差(standard mean difference,SMD)和95%可信区间(95%CI)为-0.15(-0.28～-0.02),表明AMD患者血清叶黄素水平低于正常对照组,且差异有统计学意义。结论初步得出血清叶黄素水平低与AMD发生可能存在一定关联,但需要进行更广泛地研究,确定人体血清叶黄素水平的正常范围,从而为AMD高危人群的筛查和干预提供科学依据。     

The epidemiology, economics and quality of life burden of age-related macular degeneration in France, Germany, Italy and the United Kingdom

Age-related macular degeneration (AMD) is a major public health issue, but little is known about the economics of the disease. This contribution describes the epidemiology and the economics of AMD in four European countries: France, Germany, Italy and the United Kingdom (UK). We reviewed published information on AMD, including guidelines, official statistics, and local literature and interviewed AMD experts. All available health-related quality of life studies (HRQoL) on AMD were also reviewed. Data collection focused on epidemiology, medical management and resource use (both medical and non-medical items). Prevalence of AMD among persons older than 65 years is 8% and increases with age. There are two forms of the disease: atrophic (80–85% of AMD cases) and exudative, which is characterised by choroidal neovascularisation (CNV; 15–20% of AMD cases). No treatment for the atrophic form is available. Laser photocoagulation is the mainstay of treatment for CNV, although less than 30% of persons with CNV can benefit from it. Photodynamic therapy (PDT), a new treatment for CNV, reduces the risk of vision loss in forms with predominantly visible lesions. Several other new procedures are also under development. Rehabilitation and low-vision aids are useful palliative interventions when there is a residual visual acuity. The yearly budget impact of AMD was found to be between 51.3 and 101.1 million euros in the four countries studied. Information on social services and resource use was scant and little is reported on the impact of AMD on HRQoL. Economic studies of AMD should be conducted in order to assist public health decision making.     

Predicting EQ-5D utility scores from the 25-item National Eye Institute Vision Function Questionnaire (NEI-VFQ 25) in patients with age-related macular degeneration

Purpose  In this study, we explored different statistical approaches to identify the best algorithm to predict EQ-5D utility scores from the NEI-VFQ 25 in patients with age-related macular degeneration (AMD). Methods  Ordinary least squares (OLS), Tobit, and censored least absolute deviation (CLAD) approaches were compared using cross-sectional data (primary dataset, n = 151) at screening from a phase I/II clinical trial in patients with AMD. Three models were specified in this study: full (includes all 12 dimensions of the NEI-VFQ 25), short (includes only the general health dimension and the composite score), and reduced model (using stepwise regression). To evaluate the predictive accuracy of the models, the mean absolute prediction error (MAPE), mean error, and root means squared error were calculated using in-sample cross-validation (within the primary dataset) and out-of-sample validation using an independent dataset (n = 393). The model that provided the lowest prediction errors was chosen as the best model. Results  In-sample cross-validation and out-of-sample validation consistently demonstrated that, compared to other approaches, heteroscedasticity-adjusted OLS produced the lowest MAPE (mean values were 0.1400, 0.1593, respectively) for the full model, while CLAD performed best for the short and reduced models (mean values were 0.1299, 0.1483, respectively). The normality and homoscedasticity assumptions of both OLS and Tobit were rejected. CLAD, however, can accommodate these particular violations. Conclusions  The CLAD-short model is recommended for producing the EQ-5D utility scores when only the NEI-VFQ 25 data are available.     

Chances and challenges of machine learning-based disease classification in genetic association studies illustrated on age-related macular degeneration

Imaging technology and machine learning algorithms for disease classification set the stage for high-throughput phenotyping and promising new avenues for genome-wide association studies (GWAS). Despite emerging algorithms, there has been no successful application in GWAS so far. We establish machine learning-based phenotyping in genetic association analysis as misclassification problem. To evaluate chances and challenges, we performed a GWAS based on automatically classified age-related macular degeneration (AMD) in UK Biobank (images from 135,500 eyes; 68,400 persons). We quantified misclassification of automatically derived AMD in internal validation data (4,001 eyes; 2,013 persons) and developed a maximum likelihood approach (MLA) to account for it when estimating genetic association. We demonstrate that our MLA guards against bias and artifacts in simulation studies. By combining a GWAS on automatically derived AMD and our MLA in UK Biobank data, we were able to dissect true association (ARMS2/HTRA1, CFH) from artifacts (near HERC2) and identified eye color as associated with the misclassification. On this example, we provide a proof-of-concept that a GWAS using machine learning-derived disease classification yields relevant results and that misclassification needs to be considered in analysis. These findings generalize to other phenotypes and emphasize the utility of genetic data for understanding misclassification structure of machine learning algorithms.     

Obesity, lutein metabolism, and age-related macular degeneration: a web of connections

Age-related macular degeneration (AMD) is a major cause of visual impairment in the United States. Currently there is no effective cure for this disease. Risk factors include decreased lutein and zeaxanthin status and obesity. Obesity is also an increasing public health concern. The alarming increase in the prevalence of obesity further exacerbates the public health concern of AMD. The mechanism by which obesity increases the risk of AMD may be related to the physiologic changes that occur with this condition. These include increased oxidative stress, changes in the lipoprotein profile, and increased inflammation. These changes would also result in an increased destruction and a decreased circulatory delivery of lutein and zeaxanthin to the macula of the eye. Therefore, the mechanism by which obesity is related to AMD risk may be through indirect effects on changes in lutein and zeaxanthin status and metabolism.     

年龄相关性黄斑变性合并白内障患者行白内障手术的效果观察

目的探讨AMD伴有白内障患者行白内障超声乳化吸出加蓝光滤过功能的黄色人工晶体植入术的治疗效果,评价手术的价值。方法回顾整理有AMD的白内障患者,共计39例(41只眼),均由同一术者行白内障超声乳化吸出加蓝光滤过功能的黄色人工晶体植入术。结果术后视力均较术前有不同程度的提高,经眼底血管造影检查,与术前对比,术后黄斑病变均无明显加重。结论 AMD伴有白内障患者行白内障超声乳化吸出加蓝光滤过功能的黄色人工晶体植入术有一定价值。     

Association between SNPs in miRNA-machinery genes and chronic hepatitis B in the Chinese Han population

Single nucleotide polymorphisms (SNPs) in miRNA-machinery genes can influence their generation and maturation, then expression and structure. To explore the relationship between three SNPs (rs3757 in DGCR8, rs636832 in AGO1, rs7813 in GEMIN4) in miRNA-machinery genes and chronic hepatitis B, we genotyped the SNPs by high resolution melting method (HRM) in a case-control study of 332 unrelated chronic hepatitis B patients and 352 unrelated healthy controls in Western China. Interestingly, the rs636832 was significantly associated with the susceptibility of CHB (genotype: AA/GA/GG: p = 0.010; allele: A/G: OR = 0.727, 95% CI = 0.575–0.920, p = 0.008). The minor allele A of rs636832 was significantly associated with a decreased risk of CHB. Additionally, the dominant model AG + GG vs. AA showed a risk of 1.442-fold (p = 0.018) with CHB. Further exploration for the association between rs636832 and HBV-DNA load in 329 cases showed no significant difference (genotype: p = 0.321; allele: p = 0.148). Neither did the association between rs636832 and the status of HBsAg and HbeAg (HBsAg: genotype p = 0.337, allele p = 0.436; HBeAg: genotype p = 0.861, allele p = 0.822). Our study first provided the evidence that rs636832 in AGO1 was associated with chronic HBV infection susceptibility in Chinese Han population. Further epidemiological and functional studies in larger populations are warranted to verify our results.