淋巴毒素α基因多态性与冠心病

淋巴毒素α（LT-α）是肿瘤坏死因子家族的主要成员,其主要功能是介导炎症免疫反应,从而影响细胞坏死、分化。目前,LT-α的功能、遗传差异及与冠心病的关系已成为当前心血管疾病研究的一个热点。本文阐述了LT-α的生物学特性、功能及LT-α基因多态性与冠心病的关系。     

乙醛脱氢酶2基因多态性与心血管疾病的研究进展

近年来乙醛脱氢酶2基因多态性与心血管疾病相关性研究取得一定成果。本研究对近年来乙醛脱氢酶2基因多态性与心血管疾病,如血脂、动脉粥样硬化、冠心病、心力衰竭、高血压、硝酸酯类药物的相关性研究进展进行综述。     

维生素D与心血管疾病

维生素D及其代谢产物与心血管疾病存在相关关系。本文主要对维生素D、维生素D结合蛋白及相关基因多态性与心血管疾病的关系及机制进行综述。     

血管紧张素转换酶2基因多态性与心血管疾病相关性研究进展

心血管疾病在全世界范围内患病率及病死率居高不下,肾素-血管紧张素系统在维持和改变心血管系统结构和功能方面发挥着重要作用。血管紧张素转换酶2作为肾素-血管紧张素系统新近发现与血管紧张素转换酶同源的重要一员,众多研究显示其基因多态性与原发性高血压、冠心病、心肌病、心律失常、心力衰竭等心血管疾病存在相关性。     

微粒体甘油三酯转移蛋白基因多态性与2型糖尿病血脂紊乱的关系

微粒体甘油三酯转移蛋白 (ｍｉｃｒｏｓｏｍａｌｔｒｉｇｌｙｃｅｒｉｄｅｔｒａｎｓ ｆｅｒｐｒｏｔｅｉｎ ,ＭＴＰ)是肝脏、小肠细胞合成和分泌含载脂蛋白Ｂ(ａｐｏＢ)的脂蛋白所必需的脂质转移蛋白 ,具有促进转运甘油三酯、胆固醇酯和磷脂酰胆碱的作用〔1〕。该基因启动子区域内ＭＴＰ 493位点上的单碱基突变能够影响血浆低密度脂蛋白 (ＬＤＬ)的水平〔2〕,因此认为ＭＴＰ启动子区域内的基因多态性与心血管疾病密切相关。本研究旨在了解 2型糖尿病及正常人群中ＭＴＰ基因多态性及此基因与 2型糖尿病脂质代谢的关系。一、对象和方法1.对…     

血管紧张素原基因M235T多态性与肥厚型心肌病及高血压性心肌肥厚的关系

血管紧张素原 (AGT)基因的多态性与心血管疾病的关系日益引起重视。在中国人群中 ,高血压性心肌肥厚 (HCH)和肥厚型心肌病 (HCM)在AGT基因多态性方面有何异同的研究尚少 ,本研究旨在探讨AGT基因M2 35T多态性与HCM及HCH的关系。1.资料与方法 :( 1)研究对象 :HCM组 ,40例 ,汉族 ,男2 2例、女 18例 ,平均年龄 ( 5 3 4± 19 8)岁 ,诊断符合临床和超声心动图标准 ,除外家族性遗传及高血压病、瓣膜病、先天心脏病等所致心肌肥厚 ;HCH组 ,5 0例 ,汉族 ,男 2 8例、女2 2例 ,平均年龄 ( 6 0 8± 14 5 )岁 ,高血压诊断标准符合 1978年WH…     

β1肾上腺素能受体基因多态性与运动耐量相关性的研究进展

运动耐量是衡量个体运动能力的主要指标,在评价心血管疾病的康复和预后、评估人体的体能和耐受中发挥重要作用,遗传因素是影响运动耐量的主要因素之一。许多研究表明β1肾上腺素能受体基因多态性与原发性高血压、心力衰竭等心血管疾病有重要关系,和静息心率也相关性显著,现就β1肾上腺素能受体基因多态性和运动耐量的相关性进行综述。     

肾素-血管紧张素-醛固酮系统基因多态性与心血管疾病关系的研究进展

肾素-血管紧张素-醛固酮系统在心血管疾病的发生和发展中发挥重要的作用,由遗传决定的该系统基因多态性对心血管疾病的影响成为近年来人们研究的热点之一,某些心血管疾病与某个单基因或多基因多态性密切相关。     

血管紧张素原基因M235T多态性与心血管疾病

近年来,越来越多的研究结果表明血管紧张素原基因M235T多态性与心血管疾病密切相关,通过对二者关系的研究,我们可以从分子水平上探讨心血管疾病的病因,从而为心血管疾病的防治提供新的思路。现对这一研究现状作一综述。     

PCSK9基因多态性与心血管疾病相关性的研究进展

前蛋白转化酶枯草溶菌素-9(PCSK9)能通过调节细胞膜表面低密度脂蛋白受体,影响血脂代谢,并参与动脉粥样硬化过程。近年来研究表明,PCSK9基因多态性可能与血脂异常及心血管疾病有关。现就PCSK9基因多态性与心血管疾病的研究进展做一综述。     

The role of C-reactive protein polymorphisms in inflammation and cardiovascular risk

Interest in C-reactive protein (CRP) and the association of its serum level in apparently healthy individuals to their cardiovascular disease risk has soared over the past decade. Recent studies have shown that the interindividual variations in CRP levels not only reflect environmental cues but are also a consequence of the genetic variation in the CRP gene itself. The importance of the relationship of CRP gene variants to CRP serum level and cardiovascular disease risk is important to establish CRP gene profiling as a clinical risk prediction tool and also to help test the cause-effect relationship between CRP and vascular disease. This article reviews recent studies that address the relationship of CRP gene polymorphisms to inflammation and cardiovascular risk.     

Genetic polymorphisms in platelet-related proteins and coronary artery disease: investigation of candidate genes, including N-acetylgalactosaminyltransferase 4 (GALNT4) and sulphotransferase 1A1/2 (SULT1A1/2)

Background Both platelet function and heart disease show strong genetic components, many of which remain to be elucidated. Materials and methods The roles of candidate polymorphisms in ten platelet-associated genes were compared between 1,237 Acute Coronary Syndrome (ACS) cases (with myocardial infarction and unstable angina) and 386 controls, from an Irish Caucasian population. Additionally, 361 stable angina patients were investigated. Two genes of interest were followed up in a separate Irish study of 1,484 individuals (577 with IHD and 907 unaffected). Results The GALNT4 (N-acetyl galactosaminyl transferase 4) 506I allele was significantly underrepresented in ACS (OR = 0.66, CI = 0.52-0.84; P = 0.001; P = 0.01 after correction for multiple testing), while the SULT1A1 (Sulphotransferase 1A1) 213H allele was associated with risk of ACS (OR = 1.37, CI = 1.08-1.74; P = 0.01; P = 0.1 after correction for multiple testing). Subsequent genotyping of further SNPs in GALNT4 in the family-based (IHD) group revealed that the 506I allele showed the same trend towards protecting against ACS but the haplotypic test over the four commonest haplotypes was not significant (P = 0.55). In contrast, the SULT1A1/SULT1A2 gene complex showed suggestive haplotypic association in the family-based study (P = 0.07), with the greatest increase in risk conferred by the SULT1A2 235T allele (P = 0.025). Conclusion We have identified two risk genes for cardiovascular disease, one of whose (GALNT4) effects may be on either platelet or endothelial function through modifications of PSGL1 or other important glycosylated proteins. The role of sulphotransferases (SULT1A1/2) in cardiovascular disease requires further exploration. Further validation of cardiovascular risks conferred by both genes in other populations (including gene copy number variation) is warranted.     

Introduction to the series on microRNAs in the cardiovascular system

Until recently, microRNAs (miRNAs) were considered to be relatively small players in biological systems by having a balancing function through moderate effects on gene expression levels. However, it has become appreciated that miRNAs are actually much more relevant during both development and disease, which is underscored by the attention they have been receiving. The goal of this thematic review series is to highlight current knowledge of miRNA function during cardiovascular development, their dysregulation under disease conditions and the disease modifying functions they have been shown to exert in the cardiovascular system. These reviews, in addition to discussing the recent advancements in using miRNAs as circulating biomarkers or therapeutic modalities, will hopefully be able to provide a strong basis for future research to further expand our insights into miRNA function in cardiovascular biology.     

骨保护素系统与动脉粥样硬化的关系

自最初发现骨保护素(OPG)对骨骼新陈代谢有重要的调节功能以来,因其在血管性疾病和钙化中发挥的重要作用已经引起了人们的广泛关注.在动物模型和临床研究中发现,骨保护素不仅能抑制动脉粥样硬化,而且其血清水平随着血管硬化、冠状动脉疾病和未来心血管事件的进展而升高.这一特点的确切机制和意义尚不明确.为了解其完整的作用模式,骨保护素基因多态性、钙化、炎症、凋亡及其配体之间的相互关系应纳入研究,文章将近年来骨保护素与动脉粥样硬化关系的研究进展作一综述.     

2型糖尿病和动脉粥样硬化性心血管病的关系

动脉粥样硬化性心血管病是2型糖尿病患者死亡和残疾的主要原因,2型糖尿病患者发生动脉粥样硬化病变的风险显著高于非糖尿病患者。虽然目前关于2型糖尿病与动脉粥样硬化发生和发展之间的关系尚未完全阐明,但大量基础与临床研究已证实二者之间存在密切的内在联系。现有研究提示,2型糖尿病患者发生动脉粥样硬化病变的机制可能涉及高血糖、胰岛素抵抗、血管钙化、氧化应激、内皮功能障碍和炎症反应等。结合近年来最新的研究结果,现总结分析2型糖尿病与动脉粥样硬化性心血管病之间的潜在联系与可能机制。     

醛固酮合成酶CYP11B2基因多态性与心脑血管病的研究进展

醛固酮合成酶是醛固酮合成过程中最后一步生化反应的催化酶,其编码基因为CYP11B2.醛固酮在心脑血管病的发生、发展中具有重要作用,CYP11B2基因-344T/C多态性与原发性高血压、缺血性心脏病及缺血性脑血管病密切相关.     

Inactivating germ-line and somatic mutations in polypeptide N-acetylgalactosaminyltransferase 12 in human colon cancers

Aberrant glycosylation is a pathological alteration that is widespread in colon cancer, and usually accompanies the onset and progression of the disease. To date, the molecular mechanisms underlying aberrant glycosylation remain largely unknown. In this study, we identify somatic and germ-line mutations in the gene encoding for polypeptide N-acetylgalactosaminyltransferase 12 (GALNT12) in individuals with colon cancer. Biochemical analyses demonstrate that each of the 8 GALNT12 mutations identified inactivates the normal function of the GALNT enzyme in initiating mucin type O-linked protein glycosylation. Two of these inactivating GALNT12 mutations were identified as acquired somatic mutations in a set of 30 microsatellite stable colon tumors. Relative to background gene mutation rates, finding these somatic GALNT12 mutations was statistically significant at P < 0.001. Six additional inactivating GALNT12 mutations were detected as germ-line changes carried by patients with colon cancer; however, no inactivating variants were detected among cancer-free controls (P = 0.005). Notably, in 3 of the 6 individuals harboring inactivating germ-line GALNT12 mutations, both a colon cancer and a second independent epithelial cancer had developed. These findings suggest that genetic defects in the O-glycosylation pathway in part underlie aberrant glycosylation in colon cancers, and they contribute to the development of a subset of these malignancies.     

B族维生素过量与心血管病风险

心血管疾病是一个全球性公共健康问题。在过去几十年中,心血管病呈现出全球性快速流行趋势,原因不明。B族维生素与人体的物质和能量代谢关系密切。长期摄入过量的B族维生素对人体有何影响?未引起人们的重视。最近,我们的生态学研究结果显示,美国肥胖和糖尿病流行与人均维生素B1、B2和B3(烟酸和烟酰胺)呈显著的滞后相关关系。已有的流行病学、临床和实验室证据强烈提示,长期摄入富含B族维生素的食物,特别是维生素B3(烟酸和烟酰胺)过量,可能是增加心血管病风险的主要因素之一。     

The role of mutant UDP-N-acetyl-alpha-D-galactosamine-polypeptide N-acetylgalactosaminyltransferase 3 in regulating serum intact fibroblast growth factor 23 and matrix extracellular phosphoglycoprotein in heritable tumoral calcinosis

CONTEXT: Familial tumoral calcinosis (TC) results from disruptions in phosphate metabolism and is characterized by high serum phosphate with normal or elevated 1,25 dihydroxyvitamin vitamin D concentrations and ectopic and vascular calcifications. Recessive loss-of-function mutations in UDP-N-acetyl-alpha-D-galactosamine-polypeptide N-acetylgalactosaminyltransferase 3 (GALNT3) and fibroblast growth factor-23 (FGF23) result in TC. OBJECTIVE: The objective of the study was to determine the relationship between GALNT3 and FGF23 in familial TC. DESIGN, SETTING, AND PATIENTS: We assessed the major biochemical defects and potential genes involved in patients with TC. Intervention: Combination therapy consisted of the phosphate binder Sevelamer and the carbonic anhydrase inhibitor acetazolamide. RESULTS: We report a patient homozygous for a GALNT3 exon 1 deletion, which is predicted to truncate the encoded protein. This patient had high serum FGF23 concentrations when assessed with a C-terminal FGF23 ELISA but low-normal FGF23 levels when tested with an ELISA for intact FGF23 concentrations. Matrix extracellular phosphoglycoprotein has been identified as a possible regulator of phosphate homeostasis. Serum matrix extracellular phosphoglycoprotein levels, however, were normal in the family with GALNT3-TC and a kindred with TC carrying the FGF23 S71G mutation. The tumoral masses of the patient with GALNT3-TC completely resolved after combination therapy. CONCLUSIONS: Our findings demonstrate that GALNT3 inactivation in patients with TC leads to inadequate production of biologically active FGF23 as the most likely cause of the hyperphosphatemic phenotype. Furthermore, combination therapy may be effective for reducing the tumoral burden associated with familial TC.