护骨素基因启动子区T950-C多态性与骨密度及骨代谢的关系

目的探讨绝经后汉族妇女护骨素(OPG)基因启动子区T^950-C多态性与骨质疏松症和骨代谢的关系。方法应用PCR—RFLP测定随机选取的73例绝经后骨质疏松症妇女和61例绝经后正常妇女OPG基因T^950-C的基因型，双能X线骨吸收方法分别测腰椎各椎体和股骨颈髋部的BMD，放射免疫分析法测骨代谢指标。结果所选人群OPG基因T^950-C基因型频率分布在骨质疏松症和绝经正常妇女均符合Hardy-Weinberg定律，而且其基因型在两组研究对象中分布差异无显著性，但汉族妇女T^950-C基因型分布与高加索人种妇女相比有明显差异。在骨质疏松症组CC型的股骨颈BMD低于TT型和TC型，而绝经后正常妇女三种基因型之间BMD无差异。结论OPG基因T^950-C基因型分布存在明显的种族差异。OPG基因T^950-C多态性不能作为中国汉族妇女是否发生骨质疏松症的遗传标志，但对于患有骨质疏松症的中国汉族妇女CC型却能预测骨骨质疏松症的患病程度。     

2型糖尿病患者护骨素基因启动子区950T→C多态性与血管并发症的关系

目的探讨2型糖尿病患者护骨素（OPG）基因启动子区950T→C多态性与合并冠心病、脑血管病、视网膜病变的关系。方法采用聚合酶链反应-限制性片断长度多态性（PCR—RFLP）法检测OPG基因型。结果OPG基因启动子区950T→C多态性与糖尿病合并冠心病、脑血管病无明显相关性（P〉0．05）,而与视网膜病变相关,合并视网膜病变患者C等位基因比例显著高于无视网膜病变患者（x^2=4．696,P〈0．05）。结论C等位基因可能增加2型糖尿病并发视网膜病变的遗传易感性。     

护骨素基因多态性与老年男性骨质疏松症的关系

目的探讨护骨素（OPG）基因启动子区T950C单核苷酸多态性与老年男性骨质疏松症发生的关系。方法选择98例老年男性骨质疏松症患者和101例正常老年男性,利用聚合酶链反应—限制性片段长度多态性分析技术检测OPG T950C多态位点的基因型,分析比较两组之间OPG T950C位点基因型频率的差异。结果OPGT950C基因型频率分布符合Hardy-Weinberg平衡,OPG T950C位点CC基因型频率在老年男性骨质疏松症患者和正常老年男性之间具有统计学差异（P〈0.01）。结论OPG基因启动子区T950C位点多态性与老年男性骨质疏松症的发生有关,OPG C950C基因型可能是老年男性发生骨质疏松的遗传易感性指标。     

护骨素基因C1217T多态性对应用糖皮质激素患者骨量的影响

糖皮质激素（GO）在肾脏疾病、风湿性疾病、器官移植等领域应用广泛，其长程治疗相关的骨质疏松也逐渐成为肾科医师关注的重要问题。糖皮质激素性骨质疏松症的发病率仅次于绝经后及老年性骨质疏松症而居第三位。护骨素（OPG）是肿瘤坏死因子受体超家族成员之一，OPG基因是调节骨量的一个候选基因。我们对应用糖皮质激素患者OPG基因内含子C1217T单核苷酸多态性及其与骨量、骨代谢指标之间的相关性进行了研究。     

绝经后妇女护骨素基因G1181C多态性与骨密度变化相关

目的　寻找护骨素基因(OPG)外显子中的单核苷酸多态性 (SNP),并分析其与绝经后妇女骨密度的关系。方法　在 205名绝经后妇女中,采用PCR和直接测序法确定OPG基因的SNP及基因型。应用双能X线骨密度仪测定腰椎和股骨颈骨密度 (BMD)。同时检测血清骨钙素 (BGP)、尿Ⅰ型胶原交联N端肽(NTx),以及血清护骨素(OPG)和核因子κB受体活化子配体 (RANKL)。结果　在OPG基因第一外显子中发现一个G1181C的SNP,该SNP的基因型频率分布依次为GG型占 0. 566、GC型 0. 346、CC型0. 088。去除年龄和体重的影响后,CC型的腰椎BMD明显高于GC和GG型 (P<0. 05),多元回归分析提示OPG基因型与绝经后妇女腰椎、股骨颈BMD相关 (P<0. 01)。Logistic回归分析显示OPG基因是绝经后妇女发生骨量减少和骨质疏松的独立危险因子,GG型发生骨量减少和骨质疏松的危险是CC型的 2. 83倍(P<0. 05)。结论　OPG基因的G1181C多态性与绝经后妇女BMD存在一定的关联,CC型对绝经后妇女腰椎BMD具有保护作用。     

唐山地区汉族人群血管紧张素转换酶基因多态性与冠心病的相关性研究

目的探讨血管紧张素转换酶(ACE)基因插入/缺失(insertion/deletion,I/D)多态性与冠状动脉粥样硬化性心脏病(冠心病)及冠状动脉(冠脉)病变支数间的关系。方法选取住院患者332例,其籍贯均为河北唐山地区,行冠脉造影术检查判定其是否患有冠心病及其冠脉病变支数。根据造影结果分为冠心病组(至少有一支冠脉主支血管狭窄≥50%)233例(稳定型心绞痛亚组150例、急性冠脉综合征组亚组83例)和对照组99例(任一冠脉主支血管狭窄50%)。应用聚合酶链式反应技术检测患者ACE基因I/D多态性,包括II型(插入型纯合子)、ID型(插入与缺失型杂合子)、DD型(缺失型纯合子)三组,并分析不同组别间I/D多态性差异。结果冠心病组及急性冠脉综合征亚组ACE基因DD型和D等位基因频率显著高于对照组(P0.05)。稳定型心绞痛组与对照组比较DD基因型和D等位基因频率间并无显著差异(P0.05)。不同冠脉病变支数在ACE基因型间差异无统计学意义(P0.05)。结论唐山地区汉族人群ACE基因I/D多态性中DD型和D等位基因发生率冠心病及急性冠脉综合征患者中增高,但与冠脉病变支数无关。     

汉族人群C反应蛋白基因多态性与冠心病和C反应蛋白水平相关性研究

目的研究汉族人群中C反应蛋白(CRP)基因启动子区-717A/G和-390C/A/T单核苷酸多态性(SNP)的分布以及与冠心病(CHD)和CRP水平的相关性。方法选取2007年10月至2008年5月北京医院住院患者分为CHD组(111例)及对照组(101例)。-717A/G位点运用限制性酶切长度多态性(RELP)的方法检测基因多态性,-390C/A/T位点运用序列特异性的聚合酶链反应(SSP)检测多态性。为排除其他危险因素的干扰,综合考虑与CHD相关的其他危险因素,运用Logistic回归的方法分析相关性。结果在汉族人群中-717A/G多态性各种等位基因与基因型研究对象的CRP水平差异无统计学意义,各等位基因频率和基因型频率在CHD和对照组中分布差异无统计学意义。-390C/A/T多态性与CRP水平相关,-390C/A/T多态性的等位基因频率(P<0.05)基因型频率(P<0.05)在两组之间差异有统计学意义。分析CHD相关危险因素发现该位点依然与CHD显著相关,带有T等位基因的个体得CHD的概率是不带T等位基因个体的2.66倍。结论-717A/G多态性与CRP水平和CHD未见相关;CRP基因-390C/A/...     

脂联素基因多态性与早发冠心病的相关性研究

目的:探讨早发冠心病(PCAD)与脂联素基因多态性的相关性。方法:采用病例对照研究方法,连续入选早发冠心病患者563例为病例组,412例冠状动脉造影阴性者为对照组。脂联素基因的17个SNP为候选位点,应用质谱分析的方法对单核苷酸多态性(SNP)进行分型。分析各个SNP的等位基因及基因型频率在病例组和对照组之间的差异,应用Logisitic回归方法分析各个SNP在各种遗传模型下与早发冠心病的关联。结果:脂联素基因各SNP位点的基因型和等位基因在病例组和对照组中的分布频率,差异无统计学意义(P>0.05);应用Logisitic回归方法分别在相加、显性和隐性遗传三种遗传模型下进行SNPs位点与早发冠心病的关联分析,校正混杂因素后发现在相加遗传模型下SNP+45T>G(rs2241766)多态性与中国汉族人群PCAD易感性相关(OR=1.416,95%CI:1.006~2.051,P=0.043)。结论:脂联素基因SNP+45T>G(rs2241766)多态性与中国汉族人群PCAD易感性相关。     

脂联素基因SNP+276G/T单核苷酸多态性与冠心病的相关性研究

目的探讨上海汉族人群中脂联素基因多态性分布情况，研究基因多态性与冠心病的相关性。方法采用聚合酶链反应-限制性片段长度多态性（PCR—RFLP）方法，以100例健康者为对照组，100例冠脉造影证实为冠心病的非糖尿病患者为冠心病组，研究脂联素基因单核苷酸多态性（SNP276G／T）与冠心病的相关性。结果冠心病组G／G基因型频率明显高于对照组，分别为29％和16％（P〈0．05），冠心病组G等位基因频率为45％，对照组为16％，冠心病组明显高于对照组（P〈0．05）；T等位基因频率冠心病组明显低于正常对照组，分别为55％和84％（P〈0．05）。相对于T／T基因型，G／G基因型修正后的OR值为3．93（P〈0．05），G／G＋G／T基因型的修正后的OR值为2．41。结论脂联素SNP＋276G／T各种基因型和冠心病的发病密切相关，G／G基因型很可能是冠心病的易感基因型。     

中国汉族人群APOA5-1131 T/C基因单核苷酸多态性与冠心病的相关性

目的探讨APOA5-1131 T/C单核苷酸多态性与冠心病相关性。方法对经冠状动脉造影的冠心病组168例和对照组160例,采用聚合酶链反应—限制性片段长度多态性（PCR-RFLP）方法检测APOA5-1131 T/C单核苷酸多态性,分析不同基因型与冠心病的关系。结果APOA5-1131 C等位基因频率在冠心病组明显高于对照组（P〈0.01）。相对于T/T基因型,C/C基因型修正后的OR值为2.45,P=0.01;T/C＋C/C基因型的修正后OR值为1.72,P=0.02。结论APOA5-1131 T/C单核苷酸多态性和冠心病的发病密切相关。C/C基因型很可能是冠心病的易感基因型。APOA5-1131 T/C多态性C等位基因可能是中国人群冠心病发病的危险因素之一。     

Apolipoprotein AI gene polymorphisms and risk for coronary artery disease in Chinese Xinjiang Uygur and Han population

Objective To analyze the relationship between polymorphism at the Apolipoprotein AI (Apo AI) gene and the risk for coronary artery disease. Methods A total of 107 patients (mean age 56 ±11 years) diagnosed as having stable angina pectoris (SAP) (23 cases), unstable angina pectoris (UAP) (23 cases) or myocardial infarction (MI) (61 cases) were prospectively evaluated.DNA was obtained from the 107 patients and 50 controls. In order to determine the Apo AI genotypes at two polymorphic sites (G/A at -75 bp, and C/T at+83 bp), DNA was PCR amplified and digested with MspI. Results The frequency of carriers of the rare allele at the - 75 bp site (Ml-) was 0.49 in cases and 0.30 in controls ( P< 0. 05). The frequencies of the Ml - allele among patients with SAP, UAP, MI and controls were 0. 37 (vs. controls, P > 0. 05), 0.54 (vs. controls, P < 0.05), 0.52 (vs. controls, P< 0. 05) and 0. 30, respectively. The frequencies for carriers of the rare allele at the + 83bp polymorphism (M2) were observed among patients     

C950T and C1181G osteoprotegerin gene polymorphisms in myeloma bone disease

Objectives

Bone disease is one of the hallmarks of multiple myeloma (MM). The role of osteoprotegerin (OPG) in the RANK/RANKL/OPG signaling system is well defined in the myeloma bone disease. Polymorphisms of the TNFRSF11B gene encoding OPG have been studied in various bone diseases. However, relationship between the levels of OPG and development of bone lesions regardless of RANKL is yet unknown. In this study, the effects of OPG gene polymorphism on the development of bone lesions in MM were investigated.

Methods

C950T and C1181G polymorphisms of the OPG gene were studied in 52 MM patients (36 with bone lesions and 16 without bone lesions) and in another 20 control subjects using DNA sequencing.

Results

1181 G and 950 T alleles were overrepresented in MM patients having bone lesions. 950 TT/1181 GG haplotype frequency and TT/GG combined haplotype were also higher in MM patients having bone lesions compared to MM patients without bone lesions or to control.

Discussion

This is the first study searching for the relationship between OPG gene variants C950T (promoter), C1181G (exon 1), and myeloma bone disease. It was concluded that the presence of polymorphic 1181 G/950 T alleles and 950 TT/1181 GG genotypes may play a role in the development of bone disease.     

新疆维汉两民族冠心病患者载脂蛋白AI基因多态性研究

目的　探讨新疆维汉两民族冠心病患者载脂蛋白AI基因启动子嘌呤置换突变限制性片段长度多态性。方法　用酚氯仿抽提核酸法从外周血白细胞中分离DNA ,用多聚酶链式反应 限制性片段长度多态性 (PCR RFLP)方法对新疆维汉两民族 10 7例冠心病患者和 5 0例对照组进行载脂蛋白AI(ApoAI)基因启动子嘌呤置换突变限制性片段长度多态性 (- 75bpG/A和 +83bpC/T)MspⅠ酶切研究。结果　①M1- (- 75bp位点为GA或AA)等位基因频率在冠心病组为 0 49,与对照组 (0 30 )比较有显著差别 (P <0 0 5 )。冠心病组中稳定性心绞痛 (SAP)、不稳定性心绞痛 (UAP)和心肌梗死 (MI)M1-等位基因频率分别为 0 37、0 5 4和 0 5 2 ,相互间比较无显著性差异 (P >0 0 5 )。M1-与冠心病其他危险因子一起作Logistic回归分析 ,M1- (OR =3 74,P <0 0 5 )为冠心病的危险因子之一。②M2 - (+83bp位点为CT或TT)等位基因频率在冠心病组为 0 11,与对照组 (0 12 )比较无显著差异 (P <0 0 5 )。SAP、UAP和MI中M2 -等位基因频率分别为 0 0 9、0 11和 0 12 ,相互间及与对照组比较均无显著性差异 (P >0 0 5 )。M2 -与冠心病其他危险因子一起做Logis tic回归分析 ,M2 - (OR =0 .80 ,P >0 0 5 )与冠心病无相关。结论　新疆乌鲁木齐维汉两民     

安徽地区冠心病人群冠状动脉病变特征与载脂蛋白E基因多态性的研究

目的研究安徽地区冠心病人群冠状动脉病变特征与载脂蛋白E(ApoE)基因多态性的相关性,评估其在冠心病诊疗及预防中的临床应用价值。方法收集2019年9月至2020年9月在合肥市第二人民医院心内科住院行冠状动脉造影检查的患者共199例,根据研究内容不同采用两种分组方式(分别是冠心病组和对照组,ε2、ε3和ε4组),采用PCR-荧光探针法检测ε2、ε3和ε4等位基因以及rs7412和rs429358的基因型。通过比较等位基因ε2、ε3、ε4携带者的冠状动脉病变特征,分析ApoE基因型/亚型与冠心病的发病及严重程度之间的关系。结果ε2、ε3和ε4在样本中的频率分别为13.6%、69.3%和17.1%,ApoE基因多态性与冠心病的发生有相关性(ε2:r=0.160,P<0.05;ε4:r=0.154,P<0.05);ε2、ε3和ε4组Gensini评分差异有统计学意义(P=0.026,0.013,0.001),犯罪血管狭窄程度和病变血管支数与ApoE基因多态性差异无统计学意义(ε2=0.15,ε3=0.822,ε4=0.276;ε2=0.324,ε3=0.849,ε4=0.233);犯罪血管病变类型中ε4携带者以局限性为主,差异有统计学意义(P=0.027)。结论 ApoE基因多态性与冠心病的发生具有良好的相关性,在安徽地区冠心病人群中,冠状动脉病变严重程度及犯罪血管病变类型与其相关。     

Serum osteoprotegerin and osteopontin levels are associated with arterial stiffness and the presence and severity of coronary artery disease

Background

Osteopontin (OPN) and osteoprotegerin (OPG) have recently emerged as key factors in both vascular remodeling and development of atherosclerosis. Arterial stiffness has an independent predictive value for cardiovascular events. We evaluate the relationship between OPG, OPN serum levels and vascular function in coronary artery disease (CAD) patients.

Methods

The study population was consisted of 409 subjects (280 with CAD and 129 without CAD). Carotid-femoral pulse wave velocity (PWV) was measured as an index of aortic stiffness. OPG and OPN levels were measured, as markers of vascular remodeling and calcification, by ELISA. Gensini score was used to evaluate the extent of CAD.

Results

CAD patients, compared to those without CAD, had higher OPG (3.91 ± 1.87 pmol/l vs. 2.88 ± 1.32 pmol/l, p < 0.001) and logOPN levels (1.81 ± 0.18 ng/ml vs. 1.71 ± 0.24 ng/ml, p < 0.001) and impaired PWV (8.94 ± 2.21 m/s vs. 8.28 ± 1.91 m/s, p = 0.006). Furthermore, PWV was associated with serum OPG levels (r = 0.19, p < 0.001) and with serum logOPN levels (r = 0.10, p = 0.049). Multivariate linear regression analysis revealed that increased OPG (p = 0.013) and logOPN (p = 0.006) levels are associated with 3‐vessel CAD and Gensini score (p = 0.04 for OPG and p = 0.09 for OPN), independently of other known cardiovascular risk factors.

Conclusion

The present study revealed that serum OPG and OPN levels are positively associated with arterial stiffness, and with the extent of CAD. These preliminary results suggest that OPG and OPN levels are significantly correlated with vascular function contributing to the pathogenesis of atherosclerosis in CAD. Further studies are needed to explore the mechanisms of action of OPG and OPN in CAD.     

冠心病患者腹部内脏脂肪厚度与冠状动脉狭窄程度的关系

目的探讨冠心病患者腹部内脏脂肪厚度（VFT）与冠状动脉狭窄程度的关系。方法对158例冠心病患者的冠状动脉狭窄（CAS）程度进行Gemini积分,应用超声测量VFT。结果与低值组比较,中、高值组患者腰围、体重指数、甘油三酯（TG）明显增高,高密度脂蛋白胆固醇（HDL-C）显著降低。随着VFT增加,Gensini积分明显增大。Gensini积分与年龄、腰围、体重指数、TG、低密度脂蛋白和胆固醇呈正相关,与HDL—C呈负相关。校正年龄、性别、腰围后,VFT仍然与Gensini积分相关,但进一步校正其他心血管危险因素后不再明显。结论VFT与冠状动脉狭窄程度关系密切。     

中国2型糖尿病人群脂联素受体1基因多态性与冠心病风险的相关性研究

目的 研究我国2型糖尿病(T2DM)人群脂联素受体1(AdipoR1)基因多态性与冠心病(CAD)风险的相关性. 方法 以307例T2DM患者为研究人群,其中205例伴有CAD,102例不伴CAD.应用聚合酶链式反应-限制性内切酶片断长度多态性(PCR-RFLP)技术或基因测序方法,研究AdipoR1 10个单倍型标记单核苷酸多态性(Haplotype-tagging SNPs)与CAD风险的关系. 结果 (1)Ad-ipoR1 SNP rs1342387 GG和AG基因型携带者均较AA型携带者发生CAD的风险显著增加(GG vsAA:校正OR'=2.491,95%CI' 1.354～6.885,P'=0.031;AG vs AA:校正OR'=3.053,95%CI' 1.085～5.718,P'=0.007).(2)SNP rs12045862基因型CC携带者与TT携带者相比,CAD的风险显著增加(校正OR'=2.751,95%CI' 1.063～7.115,P'=0.037).(3)SNPs rs1342387、rs12045862 GX/CC基因型组合携带者较非携带者CAD的风险显著增加(校正OR'=3.646,95%CI' 1.253～10.608,P'=0.018).保护性基因型组合AA/TX携带者较非携带者发生CAD的风险显著降低(校正OR'=0.260,95%CI'0.113～0.601,P'=0.002).(4)在超重和肥胖(BMI≥24)的T2DM人群中,发现肥胖与SNPs rs1342387、rs12045862对CAD的风险有相互作用(P<0.05);在总人群中发现的与CAD风险相关的SNPs rs1342387和rs12045862在这一亚组仍具有相关性;同时发现SNP rs7539542基因型CC携带者较GG携带者CAD的风险增加(校正OR'=4.714,P'=0.036). 结论 中国T2DM人群中,AdipoR1 SNPs与CAD的风险可能相关.在超重或肥胖T2DM人群中,AdipoR1 SNPs与肥胖对CAD风险的影响有协同作用.     

汉族人 CST3单核苷酸多态性与冠心病、胱抑素 C水平相关性研究

目的：研究胱抑素 C 基因（CST3）－157位点单核苷酸多态性（SNP）与冠心病及血胱抑素 C（Cys C）水平的相关性。方法：采用病例对照研究,入选因疑似冠心病入院的282例患者为研究对象,依据冠脉造影结果分为冠心病组（n＝130）及对照组（n＝152）。提取外周血白细胞基因组 DNA,应用巢式 PCR-直接测序技术检测 CST3－157位点 SNP,分析该位点的基因型分布及等位基因频率与冠心病、Cys C 水平的关系。结果：汉族人群中 CST3基因－157位存在 G／C 突变,存在 GG、GC 和 CC 3种基因型, GG 型为野生基因型,无论等位基因频率或者基因型分布在冠心病及对照组无明显差异,但野生基因型 Cys C 水平明显高于突变基因型。结论：汉族人群中 CST3基因－157位基因多态性与冠心病发病无直接相关性,携带野生型者血 Cys C 水平较高。     

Association of angiotensin II type 1 receptor gene A1166C polymorphism with the presence of diabetes mellitus and metabolic syndrome in patients with documented coronary artery disease

Background

There are relatively limited data available on the genetic susceptibility to diabetes mellitus and metabolic syndrome in the Iranian population. We have therefore investigated the association between the angiotensin II type I receptor gene polymorphism (AT₁R/A1166C) and the presence of diabetes mellitus and metabolic syndrome in a well defined group of patients.

Methods

Patients with angiographically defined coronary artery disease (CAD) (n = 309) were evaluated for the presence of AT₁R/A1166C polymorphism. These patients were classified into subgroups with (n = 164, M/F: 109/55) and without (n = 145, M/F: 84/61) diabetes mellitus. The AT₁R polymorphism was assessed using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) based method.

Results

There was a higher frequency of polymorphic genotypes (AC + CC) in the diabetic compared with the non-diabetic group (p = 0.01). When determined for each gender separately, this difference remained significant in the males (p = 0.04) but not in females (p = 0.09). With regard to the allele frequencies, the C allele was significantly higher and the A allele frequency was lower in the diabetic group (p = 0.01). This remained significant after gender segregation for males (p = 0.01) but not females. In the binary logistic regression analysis, only serum fasting glucose was found as the independent predictor for the presence of diabetes in the CAD patients (β = 1.16, p < 0.001 for total population and β = 1.29, p < 0.001 for male subjects). There was no significant difference in genotype or allele frequencies between subgroups with and without metabolic syndrome, this being unaffected by gender or the definition of metabolic syndrome used apart from a significantly lower frequency of C allele in male subjects with metabolic syndrome defined by the NCEP ATP III criteria (p = 0.04).

Conclusion

The AT₁R/A1166C polymorphism may be associated with the presence of diabetes mellitus in male subjects with documented CAD.