Ⅱ型对氧磷酯酶基因311Cys/Ser多态性与2型糖尿病合并冠心病关系的研究

目的:探讨型对氧磷酯酶(PON2)基因311Cys/Ser遗传多态性与2型糖尿病合并冠心病的关系。方法:应用PCR-RFLP技术,对75例老年2型糖尿病患者,其中39例2型糖尿病者合并冠心病者,36例糖尿病对照者,和38例健康对照者,检测PON2-311Cys/Ser基因多态性,等位基因以C/S表示。结果:2型糖尿病合并冠心病组与健康对照组比较,各基因型分布有显著差异(P<0.05)。S等位基因在2型糖尿病合并冠心病组明显增高;S等位基因是2型糖尿病并发冠心病的危险因素(OR=2.09,95%CI:1.04-4.22,P<0.05)。结论:PON2基因311Cys/Ser遗传多态性与中国北方地区2型糖尿病并发冠心病发病具有相关性。该酶切位点多态性具有明显的种族差异。     

PON2基因C311S、G148A多态性与脑卒中关系的研究

目的探讨对氧磷酶2（paraoxonase2,PON2）基因多态性与脑卒中的关系。方法用聚合酶链反应-限制性片段长度多态性分析法分别检测PON2基因C311S、G148A多态性在脑出血组（150例）、脑梗死组（180例）和正常对照组（120名）的基因频率。结果发现中国湖南地区人群存在PON2基因C311S、G148A多态性,在正常对照组中等位基因频率分别是S/C0.77/0.23,A/G0.43/0.57。脑出血组、脑梗死组患者PON2基因的等位基因频率与正常对照组相比差异无统计学意义（P〉0.05）。结论PON2基因多态性可能与中国湖南汉族人群脑卒中发病无关,C/S、G/A等位基因可能不是中国湖南地区汉族人群脑卒中发病的独立危险因素。     

HLA-DRB1等位基因与中国北方地区汉族人2型糖尿病大血管病变的相关性研究

目的 :探讨HLA DRB1基因多态性与 2型糖尿病 (type 2diabetesmellitus,T2DM)大血管病变的关系。方法 :采用序列特异性引物聚合酶链反应技术 (polymerasechainreactionwithsequence specificprimers ,PCR SSP)检测了中国北方地区汉族人88例T2DM患者 ( 5 2例无并发症 ,36例合并大血管病变 )HLA DRB1等位基因多态性。结果 :T2DM患者至少存在 11种HLA DRB1等位基因 ,T2DM伴大血管并发症组HLA DRB1 0 3、HLA DRB1 0 90 12基因频率明显高于无并发症组 (P <0 .0 5 )。结论 :HLA DRB1基因中DRB1 0 3、DRB1 0 90 12等位基因或其连锁不平衡基因可增高T2DM发生大血管并发症的危险性     

汉族人群载脂蛋白A5基因多态性与2型糖尿病易感性及肾损害的关系

目的：探讨载脂蛋白A5(ApoA5)基因多态性与汉族人群2型糖尿病（T2DM）易感性及肾损害的关系。方法：选取汉族T2DM患者189例（T2DM组）,且根据随机配对原则选取189例健康者（对照组）,另根据T2DM组患者肾脏检查情况将其分为肾损害者与无肾损害者。采取聚合酶链反应-限制性片段长度多态性（PCR-RFLP）检测受检对象ApoA5-1131T>C和c. 553G>T基因型及统计等位基因频率,并采用logistic回归分析法分析ApoA5基因多态性与汉族T2DM易感性及肾损害的关系。结果：T2DM组ApoA5基因-1131T>C位点的TC基因型和c. 553G>T位点的GT基因型占比均高于对照组,T2DM组-1131T>C位点等位基因C和c. 553G>T位点等位基因T频率均高于对照组,差异均有统计学意义（P<0.05）;T2DM组并发肾损害者ApoA5基因-1131T>C位点的TC基因型和c. 553G>T位点的GT基因型占比均高于无肾损害者,-1131T>C位点等位基因C和c. 553G>T位点等位基因T频率均...     

血管紧张素Ⅱ的Ⅰ型受体基因多态性和胰岛素抵抗与2型糖尿病冠心病的关系

目的　探讨血管紧张素Ⅱ的Ⅰ型受体 (typeⅠangiotensinⅡreceptor,AT1R)基因A116 6C多态性和胰岛素抵抗 (insulinresistance ,IR)与 2型糖尿病 (type 2diabetesmellitus,DM2 )冠心病的关系。方法应用PCR -RFLP法 ,对 6 2例DM2合并冠心病 (CHD)患者 ,4 9例DM2 非合并CHD患者和 10 1例正常对照组人群的AT1R基因A116 6C多态性进行检测 ;以 -log(空腹血糖×空腹胰岛素 )作为IR指标。结果　DM2 合并CHD组与DM2 非合并组比较 :AT1R基因型频率的差异无显著性 (P >0 .0 5 ) ;合并CHD组C等位基因频率显著升高 (0 .0 81vs0 .0 2 1) P <0 .0 5 ;OR =4 .2 1,95 %CI :1.0 0— 17.6 0。DM2 合并CHD组与非合并CHD组相比 ,ISI(- 2 .0 1vs- 1.77)显著升高 (P <0 .0 1)。AT1R基因多态性各基因型之间IR指标无显著性差异 (P >0 .0 5 )。结论　AT1R基因A116 6C多态性参与中国汉族人群DM 2CHD的发病 ;AT1R基因A116 6C多态性与IR无相关性 ;AT1R基因 116 6C等位基因携带者不是通过IR的影响而参与DM2 CHD的发病。     

肝脂酶基因启动子-250G/A多态性与2型糖尿病合并冠心病易感性的相关研究

目的 探讨汉族人群肝脂酶(hepatic lipase,HL)基因启动子-250G/A多态性与2型糖尿病(type 2 diabetes mellitus,T2DM)合并冠心病(coronary heart disease,CHD)的相关性.方法 采用聚合酶链反应-限制性片段长度多态性方法(polymerase chain reaction-restricted fragment length polymorphism,PCR-RFLP)检测364例T2DM+CHD组、357例T2DM组患者和356名健康对照者HL基因启动子-250G/A多态性,并分析其对脂类的影响.结果 T2DM组与对照组HL基因启动子-250G/A多态性基因型和等位基因频率差异无统计学意义(P>0.05);T2DM+CHD组GA+AA基因型频率低于对照组(0.431 vs 0.618,P=0.031);等位基因频率差异无统计学意义(P>0.05).调整混杂因素后,Spearman相关及线性回归分析,糖尿病患者(T2DM组和T2DM+CHD组),A等位基因与高密度脂蛋白胆固醇、载脂蛋白A1呈正相关;Logistic回归分析显示,A等位基因是冠心病发生的一个危险因素.结论 HL基因启动子-250G/A多态性与2型糖尿病合并冠心病的发生有关,并影响脂类代谢.     

整合素基因多态性与缺血性脑卒中及血脂的相关研究

目的 探讨整合素-α2基因(integrin alpha-2,ITGA2)C807T和整合索-β3基因(integrinbeta-3,ITGB3)T176C多态性与缺血性脑卒中的关系及其对血脂、脂蛋白水平的影响.方法 应用聚合酶链反应-限制性片段长度多态性和DNA测序的方法检测265例缺血性脑卒中患者和280名对照组ITGA2和ITGB3的基因型;同时按常规方法测定血浆脂质、脂蛋白水平.结果 缺血性脑卒中组总胆固醇(totalcholesterol,TC),甘油三酯(triacylglycerol,TG)、低密度脂蛋白-胆固醇(low density lipoprotein-cholesterol,LDL-C)水平明显高于对照组(P<0.05),ITGB3基因T176C多态性在缺血性脑卒中组和正常人群中的分布差异无统计学意义(P>0.05).而ITGA2基因C807T多态性在两组人群中的分布差异有统计学意义(P<0.05),等位基因频率的相对风险分析发现,T等位基因携带者患缺血性脑卒中的风险是C等位基因的1.455倍(OR=1.455,95%CI:1.134～1.866),携带T等位基因的缺血性脑卒中个体血浆TC水平显著高于不携带者(P<0.05).结论 ITGA2基因C807T多态性与缺血性脑卒中的发病具有相关性,其中T等位基因可能是缺血性脑卒中的遗传易感基因;ITGA2基因C807T多态性可能通过影响血脂水平而影响缺血性脑卒中的发生.     

CDKN2A/2B基因多态性与妊娠糖尿病相关

目的研究CDKN2A/2B基因rs10811661的单核苷酸多态性(SNP),探讨其与妊娠糖尿病(GDM)的相关性。方法选取鲁西南地区正常糖耐量孕妇(NGT)100例、GDM患者120例、2型糖尿病(T2DM)患者100例作为研究对象,提取基因组DNA,采用PCR-RFLP方法检测CDKN2A/2B基因rs10811661多态性。结果 CDKN2A/2B基因rs10811661的TT、TC、CC 3种基因型分布在NGT组与GDM组间有显著差别(P<0.01),GDM组危险等位基因T分布频率显著高于NGT组(P<0.05)。3种基因型及等位基因分布在NGT组与T2DM组之间亦有显著差别(P<0.05)。结论在鲁西南地区女性人群中,CDKN2A/2B基因rs10811661 T/C多态性可能与妊娠糖尿病有明显相关性。     

血管紧张素转换酶基因多态性和酗酒与缺血性脑卒中的关联

目的探讨血管紧张素转换酶（ACE）基因多态性和酗酒与缺血性脑卒中（IS）发病风险的关系。方法应用聚合酶链反应（PCR）和变性高效液相色谱（DHPLC）技术筛查了454例IS患者（病例组）和334例非IS患者（对照组）的ACE基因的多态分布，采用非条件Logistic回归模型分析基因型、酗酒情况与缺血性脑卒中患病的关系。结果与对照组相比，酗酒群体的DD基因型和D等位基因的频率显著性升高（P〈0．05），患缺血性脑卒中的相对危险度分别为8．130和2．488；而携带有Ⅱ基因型的酗酒群体患缺血性脑卒中的相对危险度则为0．389。相反。非酗酒IS患者的ACE基因的各基因型和等位基因频率的分布与对照组相比，均无显著性差异（P〉0．10）。结论携带有D等位基因的酗酒群体容易患缺血性脑卒中，但携带有I等位基因的酗酒群体不容易患缺血性脑卒中。ACE基因与酗酒在缺血性脑卒中的发病过程中存在协同作用。     

PPARY2基因Pro12Ala和C1431T多态性及其单倍型与2型糖尿病和肥胖的相关性研究

目的 研究过氧化物体增殖活化受体γ2(peroxisome proliferator activated receptorγ2,PPARγ2)基因Pro12Ala和C1431T多态性及其单倍型与汉族人2型糖尿病、肥胖的关系.方法 应用聚合酶链反应-限制性片段长度多态性的方法,对207例2型糖尿病患者和101名非糖尿病对照者进行PPARγ2基因Pro12Ala和C1431T多态性研究.结果 (1)在非糖尿病对照人群中Aal 12等位基因频率是0.064,T1431等位基因频率是0.252.单倍型分析显示Pro12Ala和C1431T两个位点连锁不平衡(D'=0.63,r2=0.074),组成了3种常见单倍型Pro-C、Pro-T和Ala-T.(2)Pro12Ala和C1431T多态性分布及其单倍型分布频率在2型糖尿病组与对照组组间差异均无统计学意义(P>0.05).(3)Pro12Ala变异与糖尿病患者的血压、血脂相关,地等位基因降低非肥胖糖尿病患者的舒张压(P<0.05),而对肥胖糖尿病患者的血脂水平无保护作用(P<0.05);C1431T多态性与糖尿病患者的超重和肥胖相关,超重和肥胖的糖尿病者T等位基因频率相对较高(P<0.05).结论 Pro12Ala和C1431T多态性可能在汉族人糖尿病发病中不是起主要作用;C1431T多态性与糖尿病患者的超重和肥胖相关.     

Paraoxonase Gene Polymorphism in South-western Korean Population

Paraoxonase (PON) has anti-atherogenic activity. Considering the important role of polymorphism in the genetic susceptibility to cardiovascular disease and the variability of its allele frequencies in different ethnic groups, the distribution of genotypes and allele frequencies of PON1M55L, PON1Q192R, PON2A148G, and PON2S311C polymorphisms was analyzed in a total 988 South-western Koreans and determined their effects on lipid parameters. The genotype distribution of PON1 at position 55 was LL=0.886, LM=0.114; and at position 192 was QQ=0.406, QR=0.594. The frequencies of the PON1 55L allele and the PON1 192R allele were similar to those seen in Chinese populations and Western populations, respectively. The genetic distribution of PON2 at position 148 was AA=0.619, AG=0.345, GG=0.035; and at position 311 was CC=0.035, SC=0.345, SS=0.619. The frequencies of the PON2 148G and 311S alleles were similar to those seen in Chinese populations. The concentrations of LDL and ApoB were significantly different between the PON2A148G (P<0.05) and PON2 S311C polymorphisms (P<0.01). PON polymorphisms and allele frequencies were described in Koreans living south-western part of Korea. These ethnic variations are considered important in the interpretation of diseases associated with PON polymorphisms.     

Paraoxonase2 C311S polymorphism and low levels of HDL contribute to a higher mortality risk after acute myocardial infarction in elderly patients

It is well known that oxidative stress plays an important role in atherosclerosis and age-related diseases. The antioxidant properties of the Human Paraoxonase gene family (PON1, 2, 3) have been widely investigated, as well as a possible role of the such gene family in cardiovascular disease. In this study, we investigated the relationship between the C311S PON2 polymorphism and the prognosis of acute myocardial infarction (AMI). We analyzed the PON2 C311S polymorphism in 442 elderly patients who had experienced an AMI. PON2 C311S genotypes were identified by PCR based analysis and analyzed as C− (SS genotype) or C+ (CS + CC) carriers. After 1 year of follow-up, the cardiovascular mortality rate in a sub-group of 295 AMI patients was calculated. We found that AMI patients carrying CS + CC genotypes (C+ carriers) had a history of type 2 diabetes mellitus, low levels of HDL-cholesterol and higher levels of TroponinT (TnT). Furthermore, we found that C+ carrier patients with low levels of HDL-cholesterol had an increased risk for mortality after 1 year of follow-up (Log Rank = 11.45, p = 0.001). Our study suggests a possible role for PON2 C311S polymorphism in the pathogenesis of cardiac ischemic damage. Patients with at least one C allele (C+ carriers) represent a category of subjects at a higher risk for the development of AMI with a worse prognosis. Our findings suggest the need for a more careful clinical monitoring in older persons with such characteristics.     

肾素-血管紧张素系统基因多态性与2型糖尿病脑梗塞的关系

目的研究肾素-血管紧张素系统(renin-angiotensin system,RAS)中血管紧张素Ⅱ的1型受体(type1angiotensin Ⅱ receptor,AT1R)基因A1166C多态及血管紧张素Ⅰ转化酶(angiotensin1-converting enzyme,ACE)基因插入/缺失(I/D)多态与中国汉族2型糖尿病(type 2 diabetes     

胆固醇酯转运蛋白基因L296Q多态性与中国人2型糖尿病和脂代谢关系的研究

目的 研究中国人群胆固醇酯转运蛋白(cholesterol ester transier protein,CETP)基因L296Q多态性与2型糖尿病及血脂水平问的关系.方法 根据血糖及甘油三脂水平将303名研究对象分4组后测糖代谢和脂代谢相关指标;应用实时荧光定量PCR技术对研究对象的CETP基因L296Q多态性进行筛查.结果 LL和LQ两种基因型的频率以及变异的296Q等位基因的频率在4组人群中的差异无统计学意义;两种基因型频率在糖尿病与非糖尿病人群问的差异也无统计学意义;LQ基因型者的血脂水平(甘油三酯,高密度脂蛋白胆固醇,总胆固醇,低密度脂蛋白胆固醇)与IJJ基因型者差异无统计学意义.结论 在中国成都地区的汉族人群中,未见CETP基因L296Q多态性与2型糖尿病相关,也未见其多态性与血脂水平变化有关.     

Association of the Pro12Ala and C1431T polymorphism of the PPAR gamma2 gene and their haplotypes with obesity and type 2 diabetes

OBJECTIVE: To study the association of the Pro12Ala and C1431T polymorphism of the PPAR gamma2 gene and their haplotypes with obesity and type 2 diabetes in Chinese population. METHODS: PCR-restriction fragment length polymorphism was used to determine the Pro12Ala and C1431T polymorphisms in 207 patients with type 2 diabetes and 101 non-diabetic control subjects. RESULTS: (1) In non-diabetic control population, the Ala allele frequency was 0.064, the T1431 allele frequency was 0.252. Haplotype analysis showed that the Pro12Ala and C1431T polymorphisms were in linkage disequilibrium (Do=0.63, r(2)=0.074), which constituted three major haplotypes Pro-C, Pro-T and Ala-T. (2) There were no significant differences of the distribution frequencies of the Pro12Ala and C1431T polymorphism and their haplotypes between the type 2 diabetes mellitus group and non-diabetic control group (P > 0.05). (3) The Pro12Ala polymorphism was associated with blood pressure and lipidemia in diabetic patients. The Ala allele significantly decreased the diastolic blood pressure of non-obese diabetic patients (P < 0.05), but it did not benefit to the obese diabetic patients for the lipidemia (P < 0.05). The C1431T polymorphism was associated with overweight and obesity in diabetic patients. The T1431 allele frequency in the body mass index >/= 25 layer was significantly higher than that in the body mass index < 25 layer (P < 0.05). CONCLUSION: The Pro12Ala and C1431T polymorphisms of the PPAR gamma2 gene might not be a major etiological factor for type 2 diabetes; the C1431T polymorphism was associated with overweight or obesity in diabetic patients.