β2-肾上腺素能受体单核苷酸多态性与心房颤动的相关性研究

目的探讨β2-肾上腺素能受体基因Arg16→Gly（46A→G）和Gin27 Glu（79C→G）两种单核苷酸多态与心房颤动的相关性。方法采用等位基因特异性聚合酶链反应（PCR）的方法。对2002～2003年北京地区的218例研究对象进行两种单核苷酸多态的检测，其中孤立性房颤组58例，高血压房颤组50例。高血压组50例，健康对照组60例。结果孤立性房颤组、高血压房颤组、高血压组及健康对照各组之间两种单核苷酸多态Arg16 Gly和Gin27 Glu的基因型频率及等位基因频率的分布差异均无显著性。但房颤组与非房颤组相比，Gly16纯合子及Gly16等位基因的频率在房颤组显著增高（P〈0．05）。结论β2-AR基因Gly16多态性与心房颤动具有相关性。     

β2-肾上腺素能受体单核苷酸多态性与心房颤动的相关性研究

目的探讨β2-肾上腺素能受体基因Arg16→Gly(46A→G)和Gln27Glu(79C→G)两种单核苷酸多态与心房颤动的相关性。方法采用等位基因特异性聚合酶链反应(PCR)的方法,对2002～2003年北京地区的218例研究对象进行两种单核苷酸多态的检测,其中孤立性房颤组58例,高血压房颤组50例,高血压组50例,健康对照组60例。结果孤立性房颤组、高血压房颤组、高血压组及健康对照各组之间两种单核苷酸多态Arg16Gly和Gln27Glu的基因型频率及等位基因频率的分布差异均无显著性,但房颤组与非房颤组相比,Gly16纯合子及Gly16等位基因的频率在房颤组显著增高(P<0.05)。结论β2-AR基因Gly16多态性与心房颤动具有相关性。     

色素上皮衍生因子启动子区基因多态性与糖尿病微血管病变的关系

目的观察色素上皮衍生因子（PEDF）启动子区单核苷酸多态性（SNP）与糖尿病微血管病变的关系。方法将271例T2DM患者分为无糖尿病微血管病变组105例,合并糖尿病微血管并发症组166例,分析PEDF基因启动子区rs12150053T／C及rs12948385G／A的基因型和等位基因频率。结果两个SNPs位点等位基因频率均有统计学差异（P〈0．05）,rs12948385位点基因型频率也有统计学差异（P〈0．05）。结论PEDF启动子区多态性位点可能是我国北方汉族人群糖尿病微血管病变发病的危险因素之一。     

CD86基因启动子－3479 A／C 位点单核苷酸多态性与 ITP 遗传易感性的关系

目的：探讨CD86基因启动子－3479 A／C位点（ rs2715267）单核苷酸多态性与原发免疫性血小板减少症（ ITP）遗传易感性的关系。方法收集93例成人慢性ITP患者（ ITP组）及119例健康对照者（对照组）,提取两组外周血DNA,采用位点特异性PCR进行DNA分型检测。分型结果通过DNA测序方法进行验证。结果 CD86基因启动子－3479 A／C位点基因型AA、AC和CC在ITP组的分布频率分别为40．9％、52．6％及6．5％,在对照组的分布频率分别为49．6％、37．8％及12．6％,两组比较P 均＞0．05;等位基因A和C在ITP组的分布频率分别为67．2％、32．8％,在对照组的分布频率分别为68．5％、31．5％,两组比较P均＞0．05。两组同性别CD86基因启动子－3479 A／C位点等位基因及基因型的分布频率比较P均＞0．05。根据糖皮质激素治疗效果将ITP患者进行分组,结果显示,激素有效组、激素无效组CD86基因启动子－3479 A／C位点等位基因及基因型的分布频率比较P均﹥0．05。结论 CD86基因启动子－3479 A／C位点的单核苷酸多态性可能与ITP的遗传易感性无关。     

急性脑梗死患者IL-18基因启动子607C／A、137G／C位点多态性观察

目的观察急性脑梗死患者白细胞介素18（IL-18）基因启动子607C／A和137G／C位点单核苷酸多态性（SNP）。方法采用型特异性引物聚合酶链反应（PCR-SSP）技术检测98例脑梗死患者（观察组）和100例健康对照者（对照组）血清IL-18基因启动子607C／A和137G／C位点多态性。结果两组607C／A位点基因型CC、CA和AA的频率及等位基因频率相比P均〉0．05。观察组组137G／C位点GG型频率显著高于对照组,GC型的频率显著低于对照组（P〈0．05）,两组等位基因频率的分布也有显著性差异（P〈0．05）。结论急性脑梗死患者IL-18基因启动子607C／A位点SNP与脑梗死无关,137G／C位点携带等位基因C可能有预防急性脑梗死的作用。     

高血压伴左心室肥厚患者ACE2350G/A及Chymase基因多态性与心房颤动的关系

目的 研究血管紧张素转换酶基因2350G→A单核苷酸多态性（ACE2350G/A）及胃促胰酶（Chymase）基因多态性在高血压伴左心室肥厚（LVH）人群中心房颤动（房颤）及非房颤患者中的分布,探讨高血压伴LVH患者房颤发生的分子遗传学机制,为房颤的防治提供临床和实验依据.方法 2010年8月至2013年6月泰州市人民医院收治的408例高血压伴LVH住院患者,根据有无房颤分为LVH-房颤组和LVH组,利用聚合酶链反应（PCR）及限制性酶切技术进行检测ACE2350G/A及Chymase基因的CMA/B多态性.结果 LVH-房颤组ACE2350基因G、A等位基因的频率明显高于LVH组（x2=5.503,P=0.019）.ACE2350基因多态性与高血压伴LVH患者房颤相关.CMA/B基因在房颤组与LVH组G、A等位基因频率差异无统计学意义（x2=0.933,P=0.334）,CMA/B基因与高血压伴LVH患者房颤发生无显著相关.与正常人相比,各类型LVH患者的CMA/B基因的GG,AA及G、A等位基因频率差异均有统计学意义.结论 ACE2350基因多态性与高血压伴LVH患者房颤发生相关,AA基因型增加房颤的发生风险,A等位基因为房颤发生的危险基因.CMA/B基因与高血压伴LVH患者房颤发生无显著相关.     

腹泻型肠易激综合征患者中IL-10基因多态性的研究

目的 探讨腹泻型肠易激综合征（D-IBS）与IL-10基因启动子区域-1082、-819和-592位点单核苷酸多态性之间的关系。方法用扩增受阻突变系统-PCR方法对41例健康对照和43例D-IBS患者IL-10基因启动子区域-1082、-819和-592位点单核苷酸多态性进行研究。结果 -819位点D-IBS患者T／T基因型频率显著高于健康对照组（67．4％比39．0％,P〈0．05）,C／T和C／C基因型频率虽较对照组低（分别为23．3％比43．9％和9．3％比17．1％）,但差异无统计学意义（P〉0．05）;-0592位点D-IBS患者A／A基因型频率显著高于对照组（67．4％比39．0％,P〈0．05）,C／A和C／C基因型频率均较对照组低（分别为23．3％比43．9％和9．3％比17．1％）,但差异无统计学意义（P〉0．05）;-1082位点基因型频率差异无统计学意义（P〉0．05）。IL-10启动子-819位点T等位基因频率在D-IBS患者显著高于健康对照组（79．1％比61．0％,P〈0．05）,C等位基因频率在D-IBS患者显著低于健康对照组（20．9％比39．0％,P〈0．05）;-592位点A等位基因频率在D-IBS患者显著高于对照组（79．1％比61．0％,P〈0．05）,C等位基因频率在D-IBS患者显著低于对照组（20．9％比39．0％,P〈0．05）;-1082位点G或A等位基因频率在D-IBS患者与对照组间差异无统计学意义。结论IL-10基因启动子区域一819T／T和-592A／A基因型可能与D-IBS发生有关。     

间隙连接蛋白40基因多态性与原发性高血压病的相关性研究

目的：探讨间隙连接蛋白40基因（44和＋71位点）多态性与原发性高血压（EH）的相关性。方法运用聚合酶链反应PCR技术对210例原发性高血压病住院患者,对照组158例体检正常人的 Cx40基因的44和＋71位点基因多态性、基因型、等位基因分布频率等进行统计学分析。结果病例组三酰甘油、钙、高密度脂蛋白（HDL）与对照组有统计学意义（P〈0.05）,CX40基因44位点基因型病例组和对照组构成比总体及男性均存在统计学意义（P〈0.05）,＋71位点无统计学意义（P〉0.05）。Logistic回归提示44位点 AA基因型、三酰甘油、钙的OR值分别是4.458、4.1330、0.195,P分别是0.039、0.001、0.014。结论 Cx40基因启动子区域44位点 AA基因型可能是男性高血压人群的危险因素,高三酰甘油为危险因素,高钙为保护因素。     

新疆维、汉两民族冠心病患者载脂蛋白 E基因启动子区多态性的关联性研究

目的：探讨新疆维、汉民族冠状动脉粥样硬化性心脏病（冠心病）患者载脂蛋白 E （ApoE）启动子区 rs405509、rs449647、rs7259620三个位点多态性的分布及其与冠心病之间的关联性。方法利用微测序（SNaPshot）单核苷酸多态性（SNP）分型技术,对201例冠心病患者（其中维族104例,汉族97例）rs405509、rs449647、rs7259620多态性进行基因分型。结果ApoE 基因启动子区 rs405509位点及 rs449647位点基因型及等位基因频率在两民族之间差异均有统计学意义（P ＜0．05）,rs7259620位点基因型及等位基因频率在两民族之间差异无统计学意义（P ＞0．05）。结论维、汉两民族冠心病患者 ApoE 启动子区 rs405509、rs449647位点等位基因多态性具有民族差异;rs7259620位点多态性无民族差异。     

内皮素受体B基因多态性与慢性阻塞性肺疾病及吸烟因素的相关性研究

目的探讨内皮素受体B（EDNRB）基因的第4外显子-30G／A处单核苷酸多态性与慢性阻塞性肺疾病（COPD）易感性及吸烟因素之间关系。方法采用PCR—RFLP技术,检测并分析EDNRB基因一30G／A（L277L）单核苷酸多态性位点在COPD组和健康对照组中的基因型频率、等位基因频率,同时分析该多态性位点与吸烟相关COPD之间是否存在相关性。结果研究发现EDNRB基因一30G／A处基因型频率分布在COPD组和对照组之间差异有统计学意义（P〈0．05）,但等位基因频率的分布在两组之间差异无统计学意义（P〉0．05）。在对COPD组和对照组中吸烟者的基因型分布频率和等位基因分布频率比较后,发现两组之间差异无统计学意义（P〉0．05）,提示该突变位点与吸烟所致的COPD之间可能无相关性存在。结论EDNRB一30G／A位点多态性可能与COPD易感性相关,与吸烟相关的COPD无关。     

Association of human connexin40 gene polymorphisms with atrial vulnerability as a risk factor for idiopathic atrial fibrillation

Alterations in distribution, density, and properties of cardiac gap junctions, which mediate electrical coupling of cardiomyocytes, are considered potentially arrhythmogenic. We recently reported 2 linked polymorphisms within regulatory regions of the gene for the atrial gap junction protein connexin40 (Cx40) at nucleotides -44 (G-->A) and +71 (A-->G), which were associated with familial atrial standstill. The present study examined whether these Cx40 polymorphisms were associated with increased atrial vulnerability in vivo and arrhythmia susceptibility. In 30 subjects without structural heart disease, of whom 14 had documented sporadic paroxysmal atrial fibrillation (AF) and 16 had no AF history, inducibility of AF was assessed using an increasingly aggressive atrial stimulation protocol. Coefficient of spatial dispersion of refractoriness (CD) was calculated. CD was defined as the SD of 12 local mean fibrillatory intervals recorded at right atrial sites, expressed as a percentage of the overall mean fibrillatory interval. Cx40 genotypes were determined by direct DNA sequencing. Subjects were stratified according to normal or increased CD with a cutoff value of 3.0, because CD >3.0 was previously shown to be strongly associated with enhanced atrial vulnerability. The prevalence of the minor Cx40 allele (-44A) and -44AA genotype was significantly higher in subjects with increased dispersion (n=13) compared with those with CD < or =3.0 (n=17; P=0.00046 and P=0.025; odds ratios of 6.7 and 7.4) and a control population (n=253; P=0.00002 and P=3.90x10(-7)). Carriers of -44AA genotype had a significantly higher CD compared with those with -44GG genotype (6.37+/-1.21 versus 2.38+/-0.39, P=0.018), whereas heterozygotes had intermediate values (3.95+/-1.38, NS). All subjects with increased CD had a history of idiopathic AF compared with only 1 subject with normal CD. The -44A allele and -44AA genotype were significantly more frequent in subjects with prior AF than in those without (P=0.0019 and P=0.031; odds ratios 5.3 and 6.2). This study provides strong evidence linking Cx40 polymorphisms to enhanced atrial vulnerability and increased risk of AF. The full text of this article is available online at http://circres.ahajournals.org.     

Polymorphisms in human connexin40 gene promoter are associated with increased risk of hypertension in men

OBJECTIVE: Gap junctions, formed by connexins (Cx), are important in the regulation of vascular tone. Previously, we reported two closely linked polymorphisms (-44G --> A and +71A --> G) within regulatory regions of the gene for Cx40, a major connexin in the vascular wall and the kidney. In the present study, we examined the hypothesis that these polymorphic variants are associated with hypertension and that they interact with blood pressure in healthy individuals. METHODS: Cx40 genotypes were determined in 191 subjects with essential hypertension, 198 normotensive individuals, and a healthy control population (178 twin pairs, 108 monozygotic, 70 dizygotic). RESULTS: We found a significant contribution of the minor Cx40 allele or genotype (-44AA/+71GG) to the risk of hypertension in men (P = 0.013 or P = 0.035; odds ratio, 1.87 or 2.10, respectively), but not in women. Moreover, in the healthy control population a significant effect of Cx40 genotype and sex on systolic blood pressure was found (P < 0.05 and P < 0.0001, respectively). Women carrying the minor Cx40 genotype had significantly higher systolic blood pressure compared with non-carriers (P < 0.05). In men, systolic blood pressure in carriers of the minor Cx40 genotype was not significantly different from the other two genotypes, possibly because of the small number of men in this group. However, men carrying the -44GA/+71AG genotype had higher standing systolic blood pressure compared with the more common Cx40 genotype (-44GG; P = 0.033). CONCLUSION: These findings suggest that the Cx40 polymorphisms may form a genetic susceptibility factor for essential hypertension in men.     

转化生长因子-β1基因+869T/C位点多态性在心房颤动发生中的意义

目的研究转化生长因子β1(transforming growth factor-β1,TGF-β1)基因+869T/C多态性与心房颤动(房颤)发生的关系,探索TGF-β1基因+869T/C基因多态性在房颤发生中的意义。方法收集2006年9月至2008年11月心内科住院患者212例,根据有无房颤将患者分为房颤组103例,对照组109例,采用序列特异性引物聚合酶链反应检测TGF-β1基因+869T/C多态性。结果在房颤组中+869T/C位点的CC基因型频率高于对照组,差异有统计学意义(35%vs.19%,P0.05),+869C等位基因频率高于其对照组,差异有统计学意义(115%vs.90%,P0.05)。方差分析显示3种基因型的左心房直径差异有统计学意义[(36.54±6.34)mm vs.(39.93±7.70)mm vs.(40.48±7.96)mm;F=5.186,P=0.006],基因型与左心房直径间的关系为:TTTCCC。结论TGF-β1+869C基因型是房颤的易感基因型;同时携带TGF-β1+869C等位基因的人群更易患房颤。     

醛固酮合酶基因-344C/T多态性与心房颤动关系的研究

目的:探讨慢性心力衰竭(CHF)患者醛固酮合酶(CYP11B2)基因-344C/T多态性与心房颤动的关系。方法:136例CHF患者被分为心房颤动组(59例)和窦性心律组(77例)。应用聚合酶链式反应-限制性片段长度多态性(PCR-RELP)分析技术对136例慢性心力衰竭的CYP11B2基因-344C/T多态性进行分析。结果:与窦性心律的心衰患者比较,CT+CC基因型更多见于合并房颤的心衰患者[(31+7)%∶(51±8)%,x2=6.29,P=0.012]。结论:慢性心力衰竭人群CYP11B2基因-344C/T多态性与心房颤动有关。     

增龄对犬肺静脉缝隙连接蛋白的影响

目的探讨增龄对犬肺静脉缝隙连接蛋白数量及分布形式的影响。方法6只成年（1～2岁）及5只老年杂种犬（〉6岁），麻醉后行心内电生理检查以评价房颤的诱发率。然后取左上肺静脉的肌袖组织，用免疫荧光共聚焦显微镜观察Cx40和Cx43的表达和分布。结果所有的成年犬均未诱发出持续性房颤，而5只老年犬中有4只诱发出了持续性房颤（χ2，P〈0，05）。Cx40和Cx43的表达和分布在两组间无显著性差异。结论增龄并不影响犬肺静脉肌袖细胞间缝隙连接蛋白的表达水平和分布形式。     

房颤患者β-纤维蛋白原-455G/A与缺血性脑血管病及纤维蛋白原相关关系的研究

目的 探讨房颤患者β-纤维蛋白原-455G/A（β-Fg-455G/A）基因多态性与血浆纤维蛋白原（Fg）水平、缺血性脑血管病的关系.方法 应用聚合酶链反应一限制性片段长度多态性方法（PCR-RFLP）检测92例房颤合并脑梗塞患者、80例单纯房颤患者和98名健康者的β-Fg-455G/A基因,并测定血浆Fg水平.结果 ①房颤合并脑梗塞组β-Fg-455G/A的A等位基因频率为0.304,房颤组为0.344,健康组为0.179,房颤合并脑梗塞组和房颤组与健康对照组比较差异有统计学意义（P〈0.05）,房颤合并脑梗塞组与房颤组比较差异无统计学意义（P〉0.05）.②房颤合并脑梗塞组血浆Fg水平为（3.83±0.59）g/L,房颤组血浆Fg水平为（3.58±0.45）g/L,健康组对照组血浆Fg为（2.79±0.36）g/L,房颤合并脑梗塞组与房颤组、健康对照组比较差异有统计学意义（P〈0.05）,房颤组与健康对照组比较差异也有统计学意义（P〈0.05）.③房颤合并脑梗塞组、房颤组和健康组A等位基因携带者的血浆Fg水平均明显高于同组G/G基因型者,差别有统计学意义（P〈0.05）.结论 β-Fg-455G/A基因的A等位基因与房颤合并脑梗塞及房颤关系密切,并且与血浆高水平的Fg有关,血浆Fg水平与房颤合并脑梗塞密切相关.     

缬沙坦联合胺碘酮治疗心房颤动的临床观察

目的：观察口服胺碘酮联合血管紧张素Ⅱ受体拮抗剂（ARB）缬沙坦治疗心房颤动的疗效,及对左心房功能的影响。方法：入选78例持续性心房颤动患者,随机分为两组,单纯口服胺碘酮（1组）36例,口服胺碘酮＋缬沙坦（11组）42例,疗程观察24个月。结果：共75例完成治疗．随访24个月,两组患者治疗12-24个月后左心房内径Ⅰ组显著高于Ⅱ组（P〈0．05）;治疗后Ⅱ组窦性心律维持12～24个月的均明显高于Ⅰ组（P〈0．05）。结论：口服胺碘酮联合缬沙坦可逆转左心房扩大,比单用胺碘酮能更有效地转复房颤,维持实性心律。     

缝隙连接蛋白40和心房颤动

随着对心房颤动机制越来越深入的了解,缝隙连接蛋白在其中扮演的作用日益受到重视。缝隙连接蛋白中的连接蛋白40在心房颤动过程中数量、分布、及分子结构都发生了变化。连接蛋白40基因突变及多态性增加了心房颤动的易患性,尽管连接蛋白40在心房颤动发生和维持中的具体机制尚未完全阐明,但一些针对连接蛋白的药物应用于心律失常有较好的效果。现就连接蛋白40与心房颤动的关系进行综述。     

A cardiac sodium channel mutation cosegregates with a rare connexin40 genotype in familial atrial standstill

Atrial standstill (AS) is a rare arrhythmia that occasionally appears to be genetically determined. This study investigates the genetic background of this arrhythmogenic disorder in a large family. Forty-four family members were clinically evaluated. One deceased and three living relatives were unambiguously affected by AS. All other relatives appeared unaffected. Candidate gene screening revealed a novel mutation in the cardiac sodium channel gene SCN5A (D1275N) in all three affected living relatives and in five unaffected relatives, and the deceased relative was an obligate carrier. In addition, two closely linked polymorphisms were detected within regulatory regions of the gene for the atrial-specific gap junction protein connexin40 (Cx40) at nucleotides -44 (G-->A) and +71 (A-->G). Eight relatives were homozygous for both polymorphisms, which occurred in only approximately 7% of control subjects, and three of these relatives were affected by AS. The three living AS patients exclusively coinherited both the rare Cx40 genotype and the SCN5A-D1275N mutation. SCN5A-D1275N channels showed a small depolarizing shift in activation compared with wild-type channels. Rare Cx40 genotype reporter gene analysis showed a reduction in reporter gene expression compared with the more common Cx40 genotype. In this study, familial AS was associated with the concurrence of a cardiac sodium channel mutation and rare polymorphisms in the atrial-specific Cx40 gene. We propose that, although the functional effect of each genetic change is relatively benign, the combined effect of genetic changes eventually progresses to total AS.