CDKN2A／B基因三个单核苷酸多态性位点与冠心病的相关性研究

目的研究CDKN2A／B基因邻近的rs2383206、rs10757274、rs10757278三个位点的单核苷酸多态性（SNP）,探讨其与冠心病的发病及冠状动脉病变程度的相关性。方法采用聚合酶链式反应（PCR）扩增CDKN2A／B基因邻近rs2383206、rs10757274、rs10757278三个SNP位点的核苷酸片段,进行多态性分型并分析其与冠心病发病的相关性,对冠心病患者冠脉造影结果进行Gensini积分评定,分析单核苷酸多态性分型与Gensini积分的关系。结果CDKN2A／B基因邻近的3个SNP位点rs2383206、rs10757274、rs10757278的AG／GG基因型分布频率均高于对照组（P〈0．05）,G等位基因分布频率高于对照组（P〈0．05）。经校正混杂因素的影响后,与AA纯合子相比rs2383206、rs10757274、rs10757278的AG／GG基因型具有显著增加冠心病风险的效应校正比值比（OR）分别为1．492,1．915,1．866。冠心病组3个SNP位点AG／GG基因型冠脉Gensini积分均高于AA基因型（P〈0．05）。结论CDKN2A／B基因的rs2383206、rs10757274、rs10757278三个单核苷酸多态性位点是昆明地区汉族冠心病发生的易感位点,且与冠状动脉病变的严重程度呈正相关。     

血清脂联素与中年男性冠状动脉病变程度的相关性研究

目的观察中年男性血清脂联素水平与冠心病发生及冠脉病变程度的相关性。方法选取经冠脉造影证实的32例冠脉粥样硬化者（冠脉狭窄〈50％）、86例冠心病患者（冠脉狭窄〉50％）,并选30例冠脉正常者作为对照组,用ELISA法进行血清脂联素的测定,同时检测体重指数（BMI）、空腹血糖（FPG）、血浆胰岛素水平（FINS）、甘油三酯（TG）和总胆固醇（TC）等相关指标,计算HOMA-IR指数。结果冠心病组及冠脉粥样硬化组血清脂联素浓度明显低于对照组（尸〈0．01）,冠心病组脂联素浓度明显低于冠状动脉粥样硬化组（P〈0．05）。冠心病组中急性冠脉综合征脂联素浓度明显低于稳定性心绞痛组（P〈0．01）。冠状动脉三支病变组、双支病变组及单支病变组血清脂联素浓度明显低于对照组（P〈0．01）。三支病变组血清脂联素水平低于单支病变组及双支病变组（P〈0．05）,而双支病变组与单支病变组血清脂联素水平差别无统计学意义（P〉0．05）。冠心病血清脂联素水平与体重指数、低密度脂蛋白（LDL-C）呈负相关（r分别为-0．291、-0．221,P〈0．05）,与HORA-IR指数呈显著负相关（r=-0.476,P〈0．01）。多元线性回归分析结果显示,HORA-IR指数是影响冠心病患者血清脂联素的最重要因素（r^2=-0．46,P〈0．01）。结论脂联素参与中年男性冠状动脉粥样硬化病变的发生发展,冠心病患者血清脂联素的水平降低,且其浓度变化与动脉粥样硬化斑块的稳定性和病变程度有关。     

高胆固醇血症患者LDL-R基因ClaI位点多态性与血清瘦素和脂联素的关系及意义

目的探讨高胆固醇血症患者低密度脂蛋白受体(LDL-R)基因第8外显子ClaI位点多态性与血清瘦素(leptin,LP)、脂联素(adiponectin,APN)的关系及意义。方法用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术结合DNA测序检测2 555例高胆固醇血症患者和2 200例体检健康者LDL-R基因的ClaI酶切位点多态性;按基因型分组,用ELISA法检测各基因型瘦素、脂联素的浓度,对两者关系进行分析,同时检测2组血脂指标。结果与健康对照组比较,高胆固醇血症组血清瘦素明显升高,脂联素、HDL-C降低(P<0.05);根据LDL-R第8外显子处是否有ClaI酶切位点,分为C+C+、C+C-、C-C-3种基因型,在C+C+组、C+C-组、C-C-组中,血清瘦素水平依次升高,脂联素水平依次降低(P<0.05);多元线性回归分析显示,基因型和胆固醇水平是影响血清瘦素、脂联素水平的独立因素。结论高胆固醇血症患者血清瘦素水平升高,脂联素水平降低,LDL-R基因C-C-基因型可能通过影响血清瘦素、脂联素水平促进高胆固醇血症的发生。     

脂联素基因G276T多态性与PCOS患者并发非酒精性脂肪性肝病的关系

目的研究脂联素基因内含子2的G276T多态性与多囊卵巢综合征（PCOS）患者并发非酒精性脂肪性肝病（NAFLD）的关系。方法采用聚合酶链反应限制性片段长度多态性检测基因型,酶联免疫吸附试验检测血清脂联素水平,比较PCOS并发NAFLD患者和PCOS患者脂联素基因内含子2的G276T基因型和等位基因频率及G276T各基因型的血清脂联素水平。结果 PCOS组血清脂联素水平显著高于PCOS并发NAFLD组,差异有统计学意义（P〈0.05）;PCOS并发NAFLD组和PCOS组中,TT、GT、GG基因型分别为8.0%、36.0%和56.0%、16.0%和51.0%、33.0%,差异有统计学意义（P〈0.05）,等位基因频率T、G分别为26.0%、74.0%和41.5%、58.5%,差异有统计学意义（P〈0.05）;PCOS并发NAFLD组中TT、GT、GG基因型之间的血清脂联素水平差异有统计学意义（P〈0.05）,PCOS组中TT、GT、GG基因型之间的血清脂联素水平差异有统计学意义（P〈0.05）。结论脂联素水平是PCOS并发NAFLD的保护因素;脂联素基因内含子2的G276T多态性与PCOS并发NAFLD有关且影响血清脂联素的水平。     

降脂治疗对冠心病患者脂联素水平的影响

脂联素（adiponectin）亦称28KD凝胶结合蛋白（GBP28），研究显示冠心病患者的脂联素水平显著下降，是冠心病发病的独立危险因素。本研究旨在了解他汀类降脂药降脂治疗对冠心病患者血清脂联素水平的影响。     

广西人群自噬相关基因ATG5的单核苷酸多态性与 ANCA相关性血管炎的关系

摘要：目的 探讨 ATG5 基因 10 个位点的单核苷酸多态性（SNP）与广西人群原发性中性粒细胞胞浆抗体 （ANCA）相关性血管炎（AAV）的关系。方法 收集符合AAV入组标准的177例患者（AAV组）和216例年龄、性别相 匹配的健康人（对照组）作为研究对象,采用多重聚合酶链反应结合高通量测序法对选定的SNP进行基因分型检测。 分析各SNP基因型与等位基因以及其构成的常见单体型在2组人群中的分布差异,并结合基因型对AAV组进行临 床资料分析。结果 （1）纳入研究的 10 个 SNP 位点分别是 rs617994、rs1766193、rs656994、rs148316514、rs573775、 rs662114、rs510432、rs506027、rs3761796、rs473543。AAV组与对照组的等位基因频率和基因型频率差异无统计学意 义（P＞0.05）。（2）10个SNP位点在研究对象中存在6个常见单体型,在AAV组和对照组中的频率差异均无统计学意 义（P＞0.05）。（3）AAV 组中 rs1766193、rs148316514 各基因型的水肿发生率,rs1766193 各基因型的发热发生率, rs617994 各基因型的血清白蛋白水平,rs510432、rs506027、rs473543 各基因型的血清白蛋白及红细胞沉降率, rs656994的各基因型中血肌酐水平差异均有统计学意义（P＜0.05）。结论 本研究中10个ATG5基因SNP位点多态 性可能与广西人群AAV遗传易感性无关,但部分可能与AAV患者的发热和水肿发生率,血清白蛋白、红细胞沉降率 和血肌酐水平存在关联。     

脂联素基因单核甘酸多态性与汉族人群肥胖易感性的关系

目的 探讨脂联素基因两个单核片酸位点多态性与汉族人群肥胖易感性的关系.方法 选取肥胖组483例,对照组517例为研究对象,用RT-PCR联合TaqMan-MGB探针检测基因型.结果 携带脂联素基因rs2241767 AG和AG/GG基因型者较AA基因型者发生肥胖的风险增加,尤其在男性、＜50岁、高血脂或不吸烟/戒烟群体中,AG/GG基因型者发生肥胖的风险增加.女性携带该基因rs12495941位点GT/TT型较GG型者发生肥胖的风险增加.结论 脂联素基因两位点(rs2241767、rs12495941)多态性改变可能与汉族人群肥胖有关.     

糖尿病合并高血压患者血清脂联素与一氧化氮、一氧化氮合酶的关系

目的：观察糖尿病合并高血压患者血清脂联素与一氧化氮、一氧化氮合酶水平变化,探讨患者血清脂联素与一氧化氮、一氧化氮合成酶的关系。方法：应用酶联免疫吸附法及硝酸还原酶比色法测定50例合并高血压糖尿病患者及30例血压正常糖尿病患者血清脂联素与一氧化、氮一氧化氮合成酶水平。结果：合并高血压糖尿病患者血清脂联素,一氧化氮、一氧化氮合成酶水平较血压正常糖尿病患者明显那降低（均P＜0.01）。合并高血压糖尿病患者血清脂联素与一氧化氮、一氧化氮合酶呈明显正相关（r=0.651,r=0.536,均P＜0.01）。结论：血清脂联素,一氧化氮、一氧化氮合酶水平降低,脂联素与一氧化氮、一氧化氮合酶相互作用相互影响,在糖尿病合并高血压的发病中发挥重要作用。     

Pin1基因多态性与喉鳞状细胞癌的相关性

目的探讨肽基脯氨酰顺反异构酶(Pin1)启动子区域的单核苷酸多态性(SNP)位点rs2233678、rs2233679与喉鳞状细胞癌(LSCC)的相关性。方法采用聚合酶链式反应-限制性内切酶片段长度多态性(PCR-RFLP)方法检测95例LSCC患者(病例组)及100例喉良性病变患者(对照组)外周血Pin1基因相关的SNP位点的差异;比较突变位点的基因型频率及等位基因型频率与患者颈淋巴结转移、临床分期的关系。结果 rs2233678多态性位点的基因型频率在病例组外周血中表达高于对照组(P<0.05),其基因型频率分布与淋巴结转移、TNM临床分期分组无关。rs2233679多态性位点的基因型频率分布在病例组和对照组中差异无统计学意义(P>0.05)。结论 rs2233678多态性位点与LSCC易感性有关。rs2233679多态性位点与LSCC易感性无关。     

糖尿病肾病患者血清脂联素水平的变化及与氧化应激的关系

目的：探讨糖尿病肾病患者血清脂联素水平的变化及与氧化应激的关系。方法：分别测定35例糖尿病肾病患者、30例单纯糖尿病患者和30例正常对照者血清脂联素、丙二醛、超氧化物歧化酶水平。结果：糖尿病肾病患者较单纯糖尿病患者血清脂联素水平明显降低,血清丙二醛水平明显升高,血清超氧化物歧化酶水平明显降低（均P〈0.01）,糖尿病肾病患者血清脂联素水平与丙二醛水平呈明显负相关（r=-0.68,P〈0.01）,与超氧化物歧化酶水平呈明显正相关（r=0.54,P〈0.01）。结论：糖尿病患者血清脂联素水平降低及所致的氧化应激增强在糖尿病肾病的发病中发挥重要作用。     

Associations between 45T/G polymorphism of the adiponectin gene and plasma adiponectin levels with type 2 diabetes

1. The purpose of the present study was to investigate the association between the single nucleotide polymorphism (SNP) 45T/G and plasma adiponectin levels and the prevalence of Type 2 diabetes mellitus (T2DM) in Uygurs of the Xinjiang region, China. 2. We performed a cross-sectional survey in a representative sample of 151 Uygur adults aged 24-80 years. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to determine the distribution of allele and genotype frequency of the SNP45 T/G polymorphism (exon 2) in the adiponectin gene. An ELISA was used to determine plasma adiponectin levels. Logistic regression was used to screen risk factors for T2DM. 3. Compared with the normal glucose tolerance (NGT) group, the T2DM group exhibited a higher distribution of the TG + GG genotype, G allele frequency and lower plasma adiponectin concentrations in TG + GG genotype carriers compared with those with the TT genotype. Compared with SNP45 T carriers, in the NGT group, G carriers had higher levels of systolic and diastolic blood pressure, low density lipoprotein (P < 0.05) and total cholesterol (P < 0.005). In the T2DM group, G carriers had lower levels of homeostasis model assessment (HOMA) of insulin sensitivity (P < 0.05) and higher levels of HOMA of insulin resistance (P < 0.05). 4. Adiponectin SNP 45 is positively correlated with the prevalence of T2DM in Uygurs of Xinjiang. The G allele carriers who have reduced plasma concentrations of adiponectin may have associated insulin resistance.     

脂联素及体质指数与女性冠状动脉粥样硬化性心脏病的关系

目的检测女性冠状动脉粥样硬化性心脏病（冠心病）患者血清脂联素及体质指数，并探讨其与冠心病的关系。方法初步诊断为冠心病的女性患者125例，其中确诊冠心病患者50例为冠心病组，非冠心病患者75例为非冠心病组。分别测量2组身高、体重获取体质指数，同时抽取肘静脉血检测脂联素。结果冠心病组患者的年龄、体质指数高于非冠心病组患者，2组相比有统计学意义。年龄（66．83±10．59）对比（63．26±11．99），（P〈0．05）；体质指数（25．68±3．41）对比（23．30±8．47），（P〈0．01）。冠心病组脂联素水平低于非冠心病组，（7．59±2．44）对比（9．62±1．11），2组之间有统计学意义（P〈0．01）。结论女性冠心病患者的年龄、体质指数和脂联素与非冠心病患者相比存在差异，脂联素是女性冠心病患者的独立危险因素。     

冠状动脉钙化积分及相关临床因素对老年冠心病的诊断研究

目的探讨多层螺旋CT冠状动脉钙化积分（CACS）及相关临床因素在老年冠心病诊断中的价值。方法入选疑诊冠心病患者106例,所有患者均行多层螺旋CT测量CACS、冠状动脉造影、外周血管彩超、心脏彩超以及相关血液生化检查。根据造影结果分为冠心病组62例（冠状动脉狭窄≥50%）,非冠心病组44例（冠状动脉狭窄〈50%）,并对冠状动脉病变严重程度进行评分。结果与对照组相比,冠心病组CACS值明显升高,且CACS值随冠状动脉狭窄程度及病变严重程度加重而增加。冠心病组颈动脉内中膜厚度（IMT）、股动脉IMT、瓣膜钙化以及血压、血脂、空腹血糖、C-反应蛋白与非冠心病组相比,差异具有统计学意义。冠心病组中瓣膜钙化较非钙化者CACS值明显升高,差异具有统计学意义。结论 CACS值与外周血管彩超、心脏彩超和相关血液生化检查相结合,能更好的预测老年冠心病的发生、发展。     

C反应蛋白与冠状动脉病变程度相关研究

目的 探讨冠状动脉病变患者血清C反应蛋白水平及其与冠状动脉病变严重程度的关系.方法 采用胶乳增强免疫比浊法测定经冠状动脉造影证实的管腔直径狭窄＞50%～95%冠状动脉病变患者血清C反应蛋白水平,与年龄、性别相匹配的冠状动脉造影证实的非冠状动脉病变患者进行比较.结果 冠状动脉病变患者血清C反应蛋白水平明显高于对照组（P＜0.05）,重度狭窄组血清c反应蛋白明显高于中度狭窄组（P＜0.05）.结论 冠状动脉病变患者血清C反应蛋白水平明显升高,可反映冠状动脉病变的严重程度.因此血清C反应蛋白水平可作为冠状动脉病变程度的参考指标之一.     

Identification of new single-nucleotide polymorphisms in the thrombin receptor gene and their effects on coronary artery diseases in Koreans

1. The thrombin receptor (the protease-activated receptor-1; PAR-1) is located on vascular cells as well as platelets and may play important roles in atherosclerotic disorders, such as coronary artery diseases (CAD). In the present study, we searched for genetic polymorphisms of the PAR-1 gene and evaluated their effects on CAD by association analysis. 2. We identified six polymorphisms in the 5'-untranslated region of the PAR-1 gene by polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP); five single-nucleotide polymorphisms (SNP) at -2355 (A to G), -2333 (T to G), -1428 (G to A), -1071 (C to T) and -561 (A to G) and a simple sequence repeat (SSR) polymorphism between -1935 and -1841. Five SNP were in strong linkage disequilibrium with each other to make three major haplotypes, the frequency of which was over 90% of all possible haplotypes. 3. For association analysis, 150 patients who had CAD (CAD+), 58 subjects who had no stenosis on the coronary angiogram and 186 reference subjects who had no clinical evidence of CAD were used from the Korean population. The genotype frequencies of the SNP were in Hardy-Weinberg equilibrium, except A-561G in CAD+. The association of these SNP as well as of the SSR with CAD was not evident. This result suggests no major roles of the PAR-1 gene in CAD in Koreans.     

Are decreased AdipoR1 mRNA levels associated with adiponectin resistance in coronary artery disease patients?

The aim of the present study was to investigate if circulating adiponectin levels and the expression of AdipoR1 and AdipoR2 in peripheral blood mononuclear cells (PBMC) are altered in coronary artery disease (CAD) patients, with and without significant stenosis, compared to healthy patients. The present study included 69 patients with presenting symptoms of CAD (26 patients with significant stenosis and 43 patients without significant stenosis). The control group (CG) consisted of 33 healthy patients. Circulating adiponectin levels were measured by enzyme‐linked immunosorbent assay, whereas AdipoR1 and AdipoR2 mRNA levels in PBMC were determined by real‐time polymerase chain reaction. Adiponectin levels were significantly higher in patients with and without significant stenosis compared to the CG (P < 0.001 vs P = 0.006, respectively). Both patient groups had lower AdipoR1 levels compared to the CG (P < 0.001 vs P < 0.001, respectively). There were no significant differences in these parameters between the two patient groups. Adiponectin negatively correlated with body mass index, triglycerides, insulin and homeostasis model assessment of insulin resistance index (HOMA IR), and positively with high‐denisty lipoprotein cholesterol in the CG. Glucose, insulin, and the HOMA IR index negatively correlated with adiponectin in patients. A positive correlation between adiponectin receptors was found in patients and the CG. Decreased AdipoR1 mRNA levels and increased circulating adiponectin in advanced stages of CAD, as well as in patients without significant stenosis, compared to the CG, implies that CAD could be related to ‘adiponectin resistance’. Despite increased adiponectin, its protective effects could be diminished even in early stages of atherosclerosis.     

冠心病合并2型糖尿病患者血浆脂蛋白a水平与冠脉病变的关系

目的:探讨冠心病(CAD)合并2型糖尿病(DM)患者血浆脂蛋白(a)[Lp(a)]水平与冠状动脉(冠脉)狭窄程度及范围之间的关系。方法:163例经冠状动脉造影(CAG)证实为CAD的2型DM患者按冠脉狭窄程度分中度(n=19)和重度(n=144)狭窄组,按病变范围分为单支(31例)、双支(48例)和多支(84例)病变组,54例无冠心病患者作为对照组,分别测量和比较各组Lp(a)、总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、载脂蛋白A-(IApoA-I)及载脂蛋白B(ApoB)水平。结果:中、重度狭窄组的Lp(a)水平高于对照组,中度狭窄组与重度狭窄组之间的Lp(a)水平差异无统计学意义。单支、双支、多支病变组Lp(a)水平高于对照组,多支病变组的Lp(a)水平高于单支、双支病变组,各组间TC、TG、HDL-C、LDL-C、ApoA-I、ApoB水平差异均无统计学意义。多元回归分析显示Lp(a)水平为冠脉狭窄程度和范围的危险因素。结论:Lp(a)水平可作为2型DM合并CAD患者冠脉病变严重性的评价指标之一。     

Biochemical investigation of rs1801282 variations in PPAR-γ gene and its correlation with risk factors of diabetes mellitus in coronary artery disease

We aimed to investigate the association of single nucleotide polymorphism of Pro/Ala (rs1801282) in peroxisome proliferator-activated receptor-gamma (PPAR-γ) gene with risk factors of diabetes mellitus (DM) in cardiovascular disease (CVD) patients. We recruited 244 participants from Faisalabad Institute of Cardiology and Department of Cardiology, Sargodha District Head Quarter Teaching Hospital, Pakistan. Out of 244 participants, 144 cases were CVD patients and 100 were healthy controls. CVD patients were further divided into 111 coronary artery disease (CAD) and 33 cardiomyopathy (CMP) patients. Assessment of variant specific polymorphism/mutation of Pro/Pro and Pro/Ala genotypes was done through amplification refractory mutation system polymerase chain reaction (ARMS-PCR). Further, serum biomarkers were measured to investigate the association among risk factors of DM and Pro/Ala polymorphism in PPAR-γ gene. About 31.5% Pro/Ala genotype was found in CVD patients out of which 22.5% were CAD patients and 9% were CMP patients. As a result, obesity, hypertension and smoking (35%, 23%, 21%, respectively) were observed to be the most critical risk factors accompanying Pro/Ala mutation in PPAR-γ particularly in CAD patients as compared to that in CMP patients. A similar pattern of association was observed among the elevated levels of glucose, cholesterol, triglyceride and ALT with Pro/Ala mutation in CAD patients. Further, CAD patients using ACE inhibitors (18%) and β-blockers (13%) were found to be the carriers of Pro/Ala genotype and also showed significant increase in glucose level. This study suggests that hyperglycaemia in CAD patients particularly obese, smokers and hypertensives having Pro/Ala polymorphism in PPAR-γ gene are at high risk of developing DM as clearly observed by hyperglycaemia in CAD patients.     

高灵敏度C反应蛋白对冠心病患者病情的判断价值

目的:评价血清高灵敏度C反应蛋白(hs鄄CRP)对冠心病患者临床病情的判断价值。方法:测定血清hs鄄CRP水平,结合冠状动脉造影,对冠心病患者临床病情进行分析评价。结果:陈旧心肌梗死(OMI)组、不稳定心绞痛(UAP)组及急性心肌梗死(AMI)组血清hs鄄CRP水平皆高于对照组,UAP组及AMI组皆高于OMI组,UAP组与AMI组间差别无统计学意义,急性冠状动脉综合征(ACS)患者三支病变组明显高于非三支病变组,血清hs鄄CRP水平与ACS患者病变血管支数呈正相关(rs=0.609,P<0.01)。结论:hs鄄CRP可能是慢性炎症引发的冠心病的危险因素,血清hs鄄CRP水平可较灵敏地反映冠心病患者临床病情的严重程度,可能为不稳定斑块的指示因子。