生长转化因子(TGF)基因型多态性与多发性骨髓瘤的相关研究

目的探讨中国北方地区汉族人生长转化因子(TGF)基因型别的多态性与多发性骨髓瘤(MM)的相关性。方法对21例MM患者采用顺序特异性引物-聚合酶链反应(PCR-SSP)方法,检测TGF基因型别的多态性变化,并与35名健康献血者对照组进行对比分析。结果 MM组TGF(H)等位基因频率(38.09%)显著高于正常对照组(11.43%),P<0.05;提示该等位基因频率增高与MM的发病相关;而TGF其它等位基因频率在MM组和对照组中无明显差异。结论我国北方地区汉族人TGF(H)基因与MM的易感性相关联。     

干扰素基因多态性与扩张型心肌病的相关研究

目的探讨北方地区汉族人干扰素（IFN-r）基因单核苷酸多态性（SNP）与扩张型心肌病（IDC）的相关性。方法应用顺序特异性引物和聚合酶链反应（PCR-SSP）技术，检测了31例IDC患者（患者组）和35例健康献血者（对照组）中IFN-r启动子基因874位点的多态性变化。结果结果表明IDC组IFN-r（874T）等位基因频率（32，26％）显著高于对照组IFN-r（11．43％），P〈0．05，两组之间比较差异有显著性意义，提示该等位基因频率增高与IDC相关。结论我国北方地区汉族人IFN-r基因874T位点的多态性在IDC的疾病病程中有重要作用，IFN-r启动子基因874T可能是IDC的易感性基因之一。     

特发性扩张型心肌病CTLA-4基因3''非翻译区(AT)n微卫星多态性研究

目的 特发性扩张型心肌病（idiopathic dilated cardiomyopathy，IDC）的发病机制与T细胞免疫应答密切相关。细胞毒性T淋巴细胞相关抗原-4（cytotoxic T lymphocyte antigen-4，CTLA-4）主要在已激活的T细胞上表达，通过与CIY28竞争结合B7，抑制T细胞过度激活，维持免疫系统内环境稳定。CTLA-4基因3’非翻译区（AT）n微卫星多态性影响CTLA-4功能。本研究旨在探讨外周血单个核细胞（PBMC）CTLA-表达状况及3’非翻译区（AT）n微卫星基因多态性与IDC的相关性。方法分别用原位杂交、免疫组化、序列特异性引物PCR等方法检测38例无血缘关系的北方汉族IDC患者以及50例正常对照者的CTLA-4mRNA、蛋白质表达、CTLA-4基因外显子3’末端非翻译区（AT）n重复序列多态性，并对PCR扩增产物进行序列分析。结果IDC组与对照组相比，PBMC经金黄色葡萄球菌肠毒素B刺激后CTLA-4mRNA、蛋白质表达强度显著减弱，且无一定规律；3’末端非翻译区共发现18种CTLA-4等位基因，与对照组比较，106bp等位基因频率在IDC患者中显著增高[22．22％ vs 1％，P=0．0002．OR=23．56，95％可信区间（CI）：9．65～83．74]。结论IDC患者CTLA-4基因转录和表达缺陷，该缺陷与CTLA-4基因3’末端非翻译区（AT）n重复序列多态性存在关联。     

特发性扩张型心肌病CTLA-4基因3′非翻译区(AT)n微卫星多态性研究

目的特发性扩张型心肌病(idiopathic dilated cardiomyopathy,IDC)的发病机制与T细胞免疫应答密切相关。细胞毒性T淋巴细胞相关抗原24(cytotoxic Tlymphocyte antigen-4,CTLA-4)主要在已激活的T细胞上表达,通过与CD28竞争结合B7,抑制T细胞过度激活,维持免疫系统内环境稳定。CTLA-4基因3′非翻译区(AT)n微卫星多态性影响CTLA-4功能。本研究旨在探讨外周血单个核细胞(PBMC)CTLA-4表达状况及3′非翻译区(AT)n微卫星基因多态性与IDC的相关性。方法分别用原位杂交、免疫组化、序列特异性引物PCR等方法检测38例无血缘关系的北方汉族IDC患者以及50例正常对照者的CTLA-4 mRNA、蛋白质表达、CTLA24基因外显子3′末端非翻译区(AT)n重复序列多态性,并对PCR扩增产物进行序列分析。结果IDC组与对照组相比,PBMC经金黄色葡萄球菌肠毒素B刺激后CTLA-4 mRNA、蛋白质表达强度显著减弱,且无一定规律;3′末端非翻译区共发现18种CTLA24等位基因,与对照组比较,106bp等位基因频率在IDC患者中显著增高[22.22%vs1%,P=0.0002,OR=23.56,95%可信区间(CI):9.65～83.74]。结论IDC患者CTLA-4基因转录和表达缺陷,该缺陷与CTLA-4基因3′末端非翻译区(AT)n重复序列多态性存在关联。     

CYP11B2基因-344T/C多态性与扩张型心肌病关联研究

目的研究CYP11B2基因4/344T/C多态性是否与汉族人扩张型心肌病关联。方法多聚酶链反应-限制性片段长度多态性技术检测扩张型心肌病和健康对照组CYP11B2基因4/344T/C多态性,χ^2验比较各组基因型和等位基因频率。结果对照组TT、TC与CC基因型频率分别为49%、46%和5%,扩张型心肌病组TT、TC与CC基因型频率分别为49%、44%和7%,经χ^2验两组之间基因型分布差异无显著性（P〉0.05）。对照组T、C等位基因频率分别为72%和28%,扩张型心肌病组T、C等位基因频率分别为71%和29%,经χ^2验两组之间等位基因分布差异亦无显著性（P〉0.05）。结论本研究尚不支持CYP11B2基因4/344T/C多态性与汉族人扩张型心肌病存在关联。     

TBX20基因启动子区的单核苷酸多态性与扩张型心肌病的相关性分析

目的:探讨TBX20基因启动子区的单核苷酸多态性(SNP)与扩张型心肌病(DCM)的相关性。方法:采用病例-对照研究方法,收集136例DCM患者和210例健康对照。采用PCR和Sanger测序的方法获得TBX20基因启动子区的SNPs。通过细胞转染和电泳迁移率变动分析(EMSA)对TBX20基因启动子区的SNPs进行遗传功能分析。采用卡方检验和两独立样本t检验对数据进行统计学分析。使用SNPStats在线软件进行相关性分析。结果:校正混杂因素后,rs73099190在共显性遗传模型和超显性遗传模型中的TC基因型和显性遗传模型中的TC+CC基因型均与DCM显著相关(OR=1.96,95%CI:1.20~3.20,P=0.019;OR=1.98,95%CI:1.22~3.24,P=0.006;OR=1.86,95%CI:1.15~3.03,P=0.012)。转染结果显示,TBX20基因启动子区的SNPs显著改变了TBX20基因启动子的转录活性(P<0.01)。进一步EMSA实验表明,rs1191745927和rs73099190影响了TBX20基因启动子与转录因子的结合。结论:DCM患者TBX20基因启动子的变异可能影响转录因子的结合,进而改变了TBX20基因的转录活性,可能作为罕见的低频危险因素促进DCM的发生发展。     

TBX20基因启动子区的单核苷酸多态性与扩张型心肌病的相关性分析

目的:探讨TBX20基因启动子区的单核苷酸多态性(SNP)与扩张型心肌病(DCM)的相关性。方法:采用病例-对照研究方法,收集136例DCM患者和210例健康对照。采用PCR和Sanger测序的方法获得TBX20基因启动子区的SNPs。通过细胞转染和电泳迁移率变动分析(EMSA)对TBX20基因启动子区的SNPs进行遗传功能分析。采用卡方检验和两独立样本t检验对数据进行统计学分析。使用SNPStats在线软件进行相关性分析。结果:校正混杂因素后,rs73099190在共显性遗传模型和超显性遗传模型中的TC基因型和显性遗传模型中的TC+CC基因型均与DCM显著相关(OR=1.96,95%CI:1.20~3.20,P=0.019;OR=1.98,95%CI:1.22~3.24,P=0.006;OR=1.86,95%CI:1.15~3.03,P=0.012)。转染结果显示,TBX20基因启动子区的SNPs显著改变了TBX20基因启动子的转录活性(P<0.01)。进一步EMSA实验表明,rs1191745927和rs73099190影响了TBX20基因启动子与转录因子的结合。结论:DCM患者TBX20基因启动子的变异可能影响转录因子的结合,进而改变了TBX20基因的转录活性,可能作为罕见的低频危险因素促进DCM的发生发展。     

CTLA-4基因多态性与特发性扩张型心肌病的相关性

目的包括细胞和体液免疫在内的自身免疫机制至少参与了部分特发性扩张型心肌病(Idiopathicdilatedcar-diomyopathy,IDC)患者的发病,且前者介导的心肌损害在IDC中更重要。CTLA-4是特异性细胞免疫的负性调节因子。本研究旨在探讨CTLA-4基因启动子-318C/T、外显子A/G多态性及3′非翻译区(AT)n微卫星多态性与IDC及血清可溶性CT-LA-4(sCTLA-4)水平的相关性。方法采用聚合酶链反应-限制性片段长度多态性(Polymerasechainreaction-restrictionfragmentlengthpolymorphisms,PCR-RFLP)方法分析黑龙江省无血缘关系汉族人群(包括72例IDC患者,100例正常健康人)CTLA-4基因-318C/T、49位点A/G多态性及3′微卫星多态性;ELISA法检测血清sCTLA-4水平。综合分析CTLA-4基因型频率、等位基因频率与IDC及sCTLA-4水平的相关性。结果IDC组外显子1GG基因型和G等位基因频率显著高于正常对照组(P=0.012,P=0.008);3′非翻译区共发现18种等位基因,106bp等位基因频率在IDC患者中显著增高(22.22%vs1%,P=0.0002,OR=23.56,95%CI9.65~83.74);两组间-318C/T多态性分布无统计学差异。与对照组相比,IDC组sCTLA-4水平显著升高[(1.87±1.06)μg/L比(0.54±0.19)μg/L,P<0.05];直线回归分析显示,IDC组GG基因型及G等位基因频率与血清sCTLA-4水平(r=0.57,P=0.021)显著相关,而AA、A/G基因型及A等位基因频率与sCTLA-4水平无相关性。启动子-318C/T多态性及3′非翻译区(AT)n微卫星多态性与sCTLA-4水平的亦无相关性。结论CTLA-4基因外显子1A49→G变异与IDC相关,携带G等位基因者易患IDC,其机制可能为该多态性造成CTLA-4信号肽中编码苏氨酸和甘氨酸的替换,从而影响蛋白翻译后加工、修饰,使sCTLA-4功能发生变化。提示3′末端非翻译区(AT)n重复序列中106bp等位基因可能是IDC的易感基因。     

HLA基因多态性与扩张型心肌病遗传易感性研究进展

扩张型心肌病(DCM)是以左心室或双心室扩大并伴有收缩功能受损为特征的心脏疾患, 其发病机制可能与遗传、病毒感染及自身免疫等有关。人类白细胞抗原(HLA)是人类最复杂的免疫调 节基因,其基因多态性控制着对于自身免疫性心肌细胞损伤的抑制性或易感性。本文就HLA基因多态 性与DCM遗传易感性相关性的研究进展作简要综述。     

Fcγ受体Ⅱ A基因多态性与冠心病和扩张型心肌病的关系

目的 炎症和免疫机制参与冠心病（CHD）和扩张型心肌病（DCM）的心肌损害。免疫球蛋白Fc受体（FcR）家族的FcγRⅡ参与免疫球蛋白介导的损伤过程,且与C反应蛋白结合,在炎症和免疫损害中起重要作用。有报道显示FcγRⅡ基因氨基酸编码131位置上的组氨酸(H/H)和精氨酸(R/R)多态性与某些炎症性和自身免疫性疾病有关。本研究旨在探讨该多态性与CHD和DCM的关系。方法 正常对照组199名,冠脉造影证实的CHD患者324名,DCM患者116名,采用PCR和变性高效液相色谱仪分析（DHPLC）研究基因多态性。结果 ①按显性效应遗传模型（HH +HR 与 RR）,DCM患者FcγRⅡA的 H显性效应频率为0.92, 较对照组0.78明显增高（P<0.001）;②按加性效应遗传模型(HH 与RR 和 HR 与RR),DCM患者H加性效应频率也明显高于对照组（P<0.01和P<0.001）;③DCM患者和对照组H等位基因频率分别为0.63和0.55,有显著性差异（P<0.05）。而CHD患者与对照组基因频率无显著差异。结论 H等位基因可能是DCM患者的易感基因,但并不是冠心病的易感基因。     

14 bp deletion polymorphism in the HLA-G gene is a risk factor for idiopathic dilated cardiomyopathy in a Chinese Han population

Human leukocyte antigen (HLA) has been reported to be associated with the pathogenesis of autoimmune-associated idiopathic dilated cardiomyopathy (IDC). However, the HLA-G in this context is limited. In the current study, a total of 117 IDC patients and age and sex matched 401 unrelated healthy controls in a Chinese Han population were HLA-G genotyped for the 14 bp insertion and deletion polymorphism. IDC patients showed markedly increased frequencies of -14 bp/-14 bp genotype [Pc = 0.00049, odds ratio (OR) = 2.17] and -14 bp alleles (Pc = 4.1 x 10(-5), OR = 1.97) when compared with healthy controls. Whereas the frequencies of +14 bp/+14 bp genotype (Pc = 0.0036, OR = 0.35) and +14 bp alleles (Pc = 4.1 x 10(-5), OR = 0.51) were significantly lower in IDC. These data, for the first time, indicated that 14 bp insertion/deletion polymorphism in HLA-G gene could be a genetic risk factor for the susceptibility to IDC.     

MHC class II genes in Mexican patients with idiopathic dilated cardiomyopathy

The purpose of the present study was to evaluate the relationship between class II major histocompatibility complex (MHC) genes (HLA-DR and HLA-DQB) and the genetic susceptibility to idiopathic dilated cardiomyopathy (IDC) in Mexican patients. The HLA-DR and DQB alleles were analyzed in 53 patients with IDC and 99 ethnically matched healthy controls using the polymerase chain reaction-sequence specific oligonucleotides (PCR-SSO) technique. IDC patients showed increased frequencies of HLA-DR4 (pC=0.02, OR=1.87), HLA-DQB1*0301 (pC=0.02, OR=1.92) and HLA-DQB1*0302 (pC=0.02, OR=1.87) when compared to healthy controls. On the other hand, IDC patients also showed decreased frequencies of HLA-DR11 allele (pC=0.03, OR=0.26) and HLA-DQB1*0201 (pC=0.04, OR=0.41). These data suggest that variation in class II HLA alleles could be a genetic factor involved in the susceptibility to IDC of the Mexican Mestizo population.     

Evolution of dilated cardiomyopathy (DCM) from idiopathic hypertrophic cardiomyopathy (IHCM) vs. inflammatory dilated cardiomyopathy (DCMi): a rare case of sudden death in an 8-year-old boy

In rare cases, the diagnosis of hypertrophic and dilated cardiomyopathy (DCM) in children was established postmortem. Our case report deals with the sudden and unexpected death of an 8-year-old boy. The postmortem examination revealed non-obstructive hypertrophy with irregular arrangement of muscular fibers, dilatation of the ventricles, endocardial fibrosis, microfocal vacuolization with enlarged hyperchromatic nuclei, and signs of inflammation with interstitial fibrosis. We present an evolution from idiopathic cardiomyopathy to DCM. To some extent, there were morphologic signs of an inflammatory process that first led us to suspect a specific inflammatory DCM.     

CTLA-4基因启动子区单核苷酸多态性与特发性扩张型心肌病的关联研究

目的探讨特发性扩张型心肌病（idiopathic dilated cardiomyopathy，IDC）患者细胞毒性T淋巴细胞相关抗原-4（cytotoxic T lymphocyte assoccated antigen 4，CTLA-4）表达状况及由CTLA-4基因启动子区单核苷酸多态性（single nucleotide polymorphism，SNP）导致的不同遗传易感性机制。方法采用限制性片段长度多态性分析151例IDC患者，120名正常健康人CTLA-4基因启动区-1772、-1661及-318位点SNP；免疫酶联吸附测定法检测血清sCTLA-4、干扰素-7及白介素-4水平；综合分析CTLA-4启动区基因型、等位基因频率及与sCTLA-4、干扰素-γ／白介素一4的相关性。结果IDC患者sCTLA-4水平与CTLA一4基因启动区SNP相关，携带-1772T／C变异者sCTLA-4表达增高。-1772TC基因型频率在IDC组尤其低射血分数亚组显著高于对照组，IDC组-1661G和-1661GG频率显著降低，具有-1772TC-1661AA及-1772TC-1661AG单倍型IDC患者sCTLA-4显著升高。结论IDC患者CTLA-4表达异常，CTLA-4基因启动区-1772C／T和-1661A／GSNP与IDC遗传易感性相关。-1772T／C变异可能影响CTLA-4基因剪接，干扰蛋白表达和功能，阻止负性调节信号传递而导致对IDC的易感。     

扩张型心肌病IL－6及IL－1活性的初步研究

应用ＭＴＴ比色法及ＣｏｎＡ活化小鼠胸腺细胞增殖法检测了３０例扩张型心肌病（ＤＣＭ）患者及２０例正常人（ＮＣ）的血清白细胞介素６（ＩＬ－６）、白细胞介素１（ＩＬ－１）的活性，结果发现ＤＣＭ患者ＩＬ－６及ＩＬ－１活性均明显高于ＮＣ组（Ｐ＜０．００１，Ｐ＜０．０１）。提示：ＩＬ－６及ＩＬ－１功能紊乱参与了ＤＣＭ的病理过程。     

Beta1-adrenergic receptor gene polymorphisms in Mexican patients with idiopathic dilated cardiomyopathy

The objective of the study was to evaluate the role of beta1-adrenergic receptor gene polymorphisms (Ser49Gly and Arg389Gly) as susceptibility markers for idiopathic dilated cardiomyopathy (IDC) in Mexican patients. The polymorphisms were analyzed in 47 patients with IDC and 93 ethnically matched healthy controls by polymerase chain reaction-restriction fragment length polymorphism. The Ser49Gly allele and genotype frequencies were similar in patients and healthy controls. On the other hand, the analysis of the Arg389Gly polymorphism showed an increased frequencies of the *Gly allele (pC = 0.022, OR = 2.16) and *Arg/*Gly genotype (pC = 0.027, OR = 2.70) in the group of IDC patients when compared to healthy controls. The data suggest that Arg389Gly polymorphism could be involved in the genetic susceptibility to develop IDC in Mexicans.     

Autosomal recessive inheritance of idiopathic dilated cardiomyopathy in a Madeira Portuguese kindred

Cardiomyopathy is a heterogeneous disorder with numerous inherited and acquired causes. Familial, isolated, dilated cardiomyopathy is usually reported as being inherited in an autosomal dominant mode with variable penetrance and expressivity. In this paper we describe a form of autosomal recessively inherited, dilated, cardiomyopathy occurring in three members of a consanguineous Madeira Portuguese family. Following review of the literature, it appears that the autosomal recessive form of dilated cardiomyopathy is more common than previously reported.