动脉粥样硬化性脑梗塞与低密度脂蛋白受体基因NcoI、AvaⅡ多态性的关系

目的 探讨动脉粥样硬化性脑梗死（atherosclerotic cerebral infarction,ACI)与低密度脂蛋白受体（low density lipoprotein receptor,LDL-R)基因NcoI、AvaⅡ多态性的关系。方法 用聚合酶链反应技术检测113名辽宁藉汉族健康人和77例ACI患者的LD－R基因NcoI、AvaⅡ多态性及血脂、载脂蛋白的含量。结果 LDL－R基因NcoI、AvaⅡ等位基因频率健康人N^ 为0．667、A^ 为0．230；ACI组N^ 为0．662、A^ 为0．125。A^-A^-与N^ N^ 联合存在时ACI的发病相对风险率（RR）为5．56（P＜0．001），引起血清TG、TC、LDL－C、LP（a)升高的相对风险率依次为4．29、7．67、9．33、3．09（P＜0．05）。结论 LDL－R基因A^-A^-与N^ N^ 联合存在影响血脂、脂蛋白的含量，与ACI密切相关。     

肾上腺髓质素基因多态性与动脉粥样硬化性脑梗死的关系

目的探讨肾上腺髓质素(adrenomedullin,ADM)基因微卫星多态性(CA重复序列)与动脉粥样硬化性脑梗死(atherosclerotic cerebral infarction,ACI)的关系。方法应用PCR,检测189名正常人和283例脑梗死患者的ADM基因型。采用放射免疫法测定262例不同基因型的脑梗死患者的血浆ADM水平,同时测定生化指标。结果脑梗死组ADM等位基因型频率分布与对照组相比较差异有统计学意义(χ2=28.732,P<0.05),在4种等位基因11,13,14,19中,等位基因19值在脑梗死组中所占的比例显著高于对照组(χ2=26.929,P<0.05),不同基因型脑梗死患者血浆ADM水平无明显差异。结论ADM基因多态性可能与动脉粥样硬化性脑梗死发生的倾向性有关。     

载脂蛋白A5基因多态性与动脉粥样硬化性脑梗死的关联研究

目的探讨载脂蛋白A5基因(apolipoprotein A5 gene,APOA5)多态性与动脉粥样硬化性脑梗死(atherosclerotic cerebral infarction,ACI)的关联性及与血脂的关系。方法用聚合酶链反应-限制性片段长度多态性分析170例ACI患者和171名健康对照-12238T>C位点多态性。结果T/C多态位点等位基因T、C频率在ACI组和正常对照组分别为0.588、0.412和0.424、0.576,等位基因T、C频率在两组间差异有统计学意义(P<0.05),且TT基因型的ACI患者其血浆甘油三酯(triglyceride,TG)水平明显高于CC型患者(P<0.05)。结论-12238T>C位点多态性可能与ACI存在关联,ACI组TT基因型可能与血浆TG水平密切相关。     

OLR1基因多态性与动脉粥样硬化性脑梗死的相关性研究

目的探讨OLR1基因3′-UTR-C188T及G501C位点多态性与动脉粥样硬化性脑梗死的相关性。方法用PCR-LDR方法检测219例动脉粥样硬化性脑梗死患者和386例健康对照者OLR1基因3'-UTR-C188T及G501C位点基因型。结果动脉粥样硬化性脑梗死组及对照组3′-UTR-C188T基因型和等位基因分布无统计学意义。病例组G501C位点的CC+GC基因型、GC基因型频率明显高于对照组(P=0.04,P=0.03)。病例组G501C位点的GC基因型频率,在校正传统危险因素后仍明显高于对照组,且差异有统计学意义(OR=1.535,95%CI=1.044-2.256,P=0.03)。结论 OLR1基因G501C位点多态性与动脉粥样硬化性脑梗死的发病具有相关性,可能是动脉粥样硬化性脑梗死发病的危险因素。     

基因多态性在2型糖尿病大血管病变预测中的意义

2型糖尿病是一种多基因遗传性疾病 ,其大血管并发症的发生同样与遗传因素密切相关。与肥胖及胰岛素抵抗、血脂、血压、血凝等方面有关的基因多态性 ,可能在 2型糖尿病大血管病变发生的预测中起着某种作用。如何在众多的候选易感基因中筛选出最有预测价值的基因正成为今后临床与基础研究的新热点之一 ,有针对性的基因治疗亦有望成为预防 2型糖尿病大血管病变综合治疗的重要途径之一。     

MTNR1B基因多态性与2型糖尿病

2型糖尿病是一种与多基因、多因素相关联的具有明显遗传异质性的疾病.全基因组关联分析显示MTNR1B基因变异与胰岛素分泌、葡萄糖水平以及2型糖尿病发病有显著相关性.MTNR1B基因是2型糖尿病重要的易感基因之一,其变异可能通过减少β细胞胰岛素分泌,从而增加2型糖尿病的易感性.     

MTNR1B基因多态性与2型糖尿病

2型糖尿病是一种与多基因、多因素相关联的具有明显遗传异质性的疾病.全基因组关联分析显示MTNR1B基因变异与胰岛素分泌、葡萄糖水平以及2型糖尿病发病有显著相关性.MTNR1B基因是2型糖尿病重要的易感基因之一,其变异可能通过减少β细胞胰岛素分泌,从而增加2型糖尿病的易感性.     

NAT2基因多态性与2型糖尿病的关系

目的探讨NAT2基因多态性与2型糖尿病易感性的关系,为糖尿病的有效防治提供科学依据。方法采用PCR及测序技术对174例2型糖尿病患者和174例健康者的NAT2基因4个常见突变位点进行检测。结果糖尿病组中NAT2等位基因频率分别为：Wt（69.54%）,M2（16.37%）,M3（10.63%）,M1（3.44%）。与正常对照组比较差异无显著性。NAT2基因型（WT/WT,WT/Mx,Mx/Mx）在糖尿病组中分布频率分别为44.82%,49.42%,5.74%,两组间比较差异显著。糖尿病组中快乙酰化者164例（占94.25%）,慢乙酰化者10例（占5.75%）,两组间比较有差异。携带NAT2快乙酰化基因型者患2型糖尿病的风险是携带NAT2慢乙酰化基因型者的3.98倍。结论本研究提示快乙酰化代谢表型可能是糖尿病的一个遗传易感因素,而慢乙酰化代谢表型可能对糖尿病的发生具有一定保护作用。     

2型糖尿病家系与尾加压素2基因多态性

目的探讨我国常州地区汉族家系2型糖尿病与尾加压素2(urotensinⅡ,UT-Ⅱ)基因rs228648多态性位点的关系。方法采用家系内外对照的病例对照研究,并设置无家族史的普通病例组,应用聚合酶链反应-限制性片段长度多态性技术,对rs228648(G/A)多态性进行基因分型。结果家系中携带AG和AA基因型者患病风险分别为GG型的1.98(95%可信区间=1.19～3.29)和2.46(95%可信区间=1.39～4.34)倍,家系病例组A等位基因频率高于内对照组及普通病例组(P=0.01)。内对照组A等位基因频率高于外对照组(P=0.001)。内对照组携带AG基因型者的胰岛素抵抗指数、胰岛素敏感指数以及胰岛初期分泌功能指数均高于GG基因型者(P<0.05)。结论rs228648多态性位点变异可能是2型糖尿病的危险因素之一,家系人群该基因变异与其胰岛功能间存在关联。     

Hcy、MTHFR基因多态性与急性脑梗死的关系

目的：探讨同型半胱氨酸（Homocysteine,Hcy）及亚甲基四氢叶酸还原酶（MTHFR）基因多态性与急性脑梗死的关系。方法：选取98名急性脑梗死患者以及98名健康志愿者进行性别、年龄和体重指数配对,检测并分析比较两组血浆Hcy浓度以及MTHFR677位点基因型。结果：急性脑梗死组和对照组的Hcy浓度分别为（16.83±5.86）μmol/L和（14.20±5.73）μmol/L,经统计学处理,差异具有统计学意义（P〈0.01）。急性脑梗死组的T等位基因频率（58.2%）显著高于对照组（40.8%）（χ2=11.80,P〈0.01）。急性脑梗死组CC、CT和TT基因型相应的Hcy浓度分别为（14.34±5.25）μmol/L、（16.12±5.87）μmol/L和（18.96±5.58）μmol/L,差异具有统计学意义（F=5.36,P〈0.05）,TT型显著高于CC型与CT型（P值分别为0.002;0.031）。结论：MTHFR基因C677T突变可影响Hcy水平,可能是急性脑梗死的重要发病机制之一。     

基质金属蛋白酶-3血清水平及启动子基因5A/6A多态性与动脉粥样硬化性脑梗死的关系

目的 探讨摹质金属蛋白酶-3(matrix metalloproteinase-3,MMP-3)血清水平及启动子基因5A/6A多态性与动脉粥样硬化性脑梗死(atherosclerotic cerebral infarction,ACI)的关系.方法 对215例ACI患者和226名健康体检者进行研究.采用ELISA法测定血清MMP-3水平,同时采用聚合酶链反应-限制性片段长度多态性方法分析MMP-3启动子基因5A/6A多态性.结果 ACI组发病48 h内的血清NIVIP-3水平为(23.28±12.19)ng/μL,较对照组(2.76±2.25)ng/μL显著增高(t=24.867,P=0.000).Aa组内5A/6A+5_4/5.4基因型患者外周血MNP-3水平为(26.04±11.79)ng/μg,6A/6A基因型患者外周血MMP-3水平为(22.24±12.21)ng/mL,两者间差异有统计学意义(t=2.057,P=0.041).ACI组5A./6A+5A/5A基因型频率为27.4%,对照组为15.5%,两者比较差异有统计学意义(x2=9.389,P=0.1102),5A等位基因频率在ACI组为14.2%,对照组为7.7%,两者比较差异也有统计学意义(X2=9.430,P=0.002).结论 ACI患者发病48h内血清MMP-3水平显著增高,MMP-3启动子基因5A/6A多态性可能与MMP3的血清水平及ACI发生倾向性有关.     

Polymorphisms of the lipoprotein lipase gene are associated with atherosclerotic cerebral infarction in the Chinese

BACKGROUND: Lipoprotein lipase (LPL), which plays an essential role in plasma lipoprotein metabolism and transportation, appears to be a risk factor for ischemic vascular diseases. Several studies have recently reported the presence of relationship between HindIII, PvuII, Ser447Ter (C-->G) polymorphisms of LPL and ischemic vascular diseases. PURPOSE: We first studied the relationship between LPL polymorphisms and the risk of atherosclerotic cerebral infarction (CI) by detecting the frequencies of LPL HindIII, PvuII and Ser447Ter genotypes and combined genotypes in the Chinese. METHODS: We recruited 185 CI patients, confirmed by cranial computed tomography or magnetic resonance imaging/angiography, or both, and 186 control subjects. Polymerase chain reaction-restriction fragment length polymorphisms technique was used to detect HindIII, PvuII and Ser447Ter polymorphisms of the LPL gene. RESULTS: The frequencies of the H+H+ genotype and H+ allele did not differ between CI and control groups. The frequencies of the P+P+ genotype and P+ allele gene were significantly higher in the CI group (P=0.040, P=0.015). The frequencies of CG+GG genotype and G allele were lower in the CI group (P<0.001, P<0.001). In the CI group, the individuals with P+P+ genotype had a significantly higher level of plasma triglyceride (TG) and a lower level of plasma high density lipoprotein cholesterol (HDL-c). CG+GG genotypes were correlated with significantly higher levels of plasma total cholesterol (TC), HDL-c and low density lipoprotein cholesterol (LDL-c) in the CI group. The frequencies of H+/C and P+/C combined genotypes were higher in the CI group than in controls (P<0.001, P<0.001). The frequency of H+/P+/C combined genotype was significantly higher in the CI group than in controls (P<0.001). CONCLUSIONS: Our study suggests that PvuII and Ser447Ter polymorphisms are associated with lipid profile and CI.     

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。     

脂蛋白脂酶Ser447Ter基因多态性与动脉硬化性脑梗死的相关研究

目的研究脂蛋白脂酶（lipoprotein lipase，LPL）Ser447Ter基因多态性与动脉粥样硬化性脑梗死（atherosclerotic cerebral infarction, CI）发病的关系及其对血脂水平、颈动脉斑块的影响。方法对166例CI患者及72名健康成人采用聚合酶链反应-限制性片段长度多态性方法检测LPL-Ser447Ter基因多态性，颈动脉超声多普勒检查颈总动脉内膜中层厚度（intima-media thickness，IMT）和颈动脉斑块（carotid artery plaque，CAP）的形状及大小。结果CI组CG＋GG基因型甘油三酯（triglyceride，TG）含量比CC基因型明显降低（P=0．1301），高密度脂蛋白胆固醇（high density lipoprotein cholesterol，HDL-C）含量明显增高（P=0．007）；对照组CG＋GG基因型TG含量比CC基因型低（P=0．041）；CI组G等位基因频率低于对照组（P=0．014）；LPLSer447Ter基因多态性与颈总动脉IMT和CAP分级无明显相关。结论LPL Ser447Ter基因多态性与血脂变化及脑梗死的关系密切，G等位基因可能引起血TG降低、HDL-C升高；G等位基因可能是脑梗死的保护基因型．     

Metabolic Syndrome with Hyperglycemia and the Risk of Ischemic Stroke

Purpose

The association of ischemic stroke and metabolic syndrome (MetSyn) with or without diabetes mellitus (DM) is not clear. The present study aimed to identify the impact of diabetes or hyperglycemia on the risk of MetSyn-associated ischemic stroke.

Materials and Methods

This study comprised an Asian population of 576 patients with acute nonembolic cerebral infarction and 500 controls. MetSyn was defined according to the criteria of the International Diabetes Federation. MetSyn patients were further subgrouped according to their glucose levels: MetSyn with DM, MetSyn with impaired fasting glucose (IFG) and MetSyn with normal glucose tolerance (NGT). The impact of MetSyn on cerebral infarction was then evaluated.

Results

At baseline, the prevalence of MetSyn in patients with cerebral infarction was higher than that of the controls (57.29% vs. 10.00%, p<0.01). In the stroke group, the prevalences of MetSyn with DM, IFG, and NGT were 25.69%, 8.85% and 22.74%, respectively, all of which were higher than that of the controls (all p-values <0.05). By multiple logistic regression analysis, we discovered that MetSyn was associated with an increased risk of cerebral infarction (odds ratio: 5.73, p<0.01). After adjustment for all the components of MetSyn, the odds ratios of MetSyn with DM, IFG, and NGT were 5.70, 2.24 and 2.19 (all p-values <0.05), respectively.

Conclusion

In Asian population, patients with MetSyn accompanied by T2DM are at the greatest risk for acute non-embolic stroke. Additionally, IFG was not observed to be associated with an increased risk for MetSyn-related ischemic stroke.     

The Association of Mitofusion-2 Gene Polymorphisms with Susceptibility of Essential Hypertension in Northern Han Chinese Population

Background: Mitofusion-2 (Mfn2) played an important role in regulating vascular smooth muscle cells proliferation, insulin resistance and endoplasmic reticulum stress, which were found to be involved in the development of hypertension. So we inferred that the Mfn2 gene may participate in the pathogenesis of hypertension. The aim of this study was to determine whether common single nucleotide polymorphisms (SNPs) in Mfn2 gene were associated with essential hypertension (EH) in northern Han Chinese.Methods: We genotyped 6 tagging SNPs of Mfn2 gene (rs2336384, rs2295281, rs17037564, rs2236057, rs2236058 and rs3766741) with the TaqMan assay in 626 hypertensive patients and 618 controls.Results: Logistic regression analysis indicated that CC+CA genotype of rs2336384 and AA+AG genotype of rs2236057 were significantly associated with increased risk of EH (OR=1.617, P=0.005; OR=1.418, P=0.031, respectively). GG genotype of rs2236058 and GG+CG genotype of rs3766741 were found to be significantly associated with decreased risk of EH (OR=0.662, P=0.023; OR=0.639, P=0.024).When stratified by gender, for rs2336384, rs2236057 and rs2236058, significant association was observed in males, but not in females. Haplotype analysis indicated that the CCAACC haplotype was positively correlated with EH and there was a negative correlation between ACAGGG haplotype and EH.Conclusions: This study demonstrated that Mfn2 gene polymorphisms were associated with essential hypertension in northern Han Chinese population, especially in male subjects.     

Proinflammatory Cytokine Gene Polymorphisms among Iranian Patients with Asthma

Introduction  Asthma is one of the most common respiratory diseases caused by acute and chronic inflammation of airways. Proinflammatory cytokines could contribute to this inflammatory process. This study was performed in order to analyze the genetic profile of proinflammatory cytokines in Iranian asthmatic patients. Patients and Methods  The allele and genotype frequencies of a number polymorphic genes coding for tumor necrosis factor (TNF)-α, interleukin (IL)-1α, IL-1β, IL-1 receptor (IL-1R), IL-1RA, and IL-6 were investigated in 60 patients with asthma in comparison with 140 controls using polymerase chain reaction with sequence-specific primers. Results  The most frequent genotypes in our patients were TNF-α GA at position −308 (P = 0.001), TNF-α AA at position −238 (P = 0.01), IL-1α TC at position −889 (P = 0.0001), IL-1β TC at position −511 (P = 0.0001), and IL-1RA TC at position Mspa-I 11100 (P = 0.001). In contrast, the frequencies of the genotypes TNF-α GG at position −308 (P = 0.001), IL-1α CC at position −889 (P = 0.005), IL-1β CC at position −511 (P = 0.0001), and IL-1RA TT at position Mspa-I 11100 (P = 0.0001) in the patient group were significantly lower than controls. The most frequent haplotypes for TNF-α (positions 308, −238) was A/A in the patient group in comparison with controls (P = 0.0001). Conclusion  While environmental factors are important in the development of asthma, genetic factors could have a critical role in the expression of the disease. Considering the high frequency of presence of TNF-α AG genotype (−308), it seems that the production of TNF-α in the asthmatic patients could be higher than normal subjects.     

用PCR—RFLP方法检测动脉硬化性脑梗死患者的载脂蛋白E基因多态性分布

目的 研究动脉硬化性脑梗死（ＡＣＩ）患者中的载脂蛋白Ｅ（ＡｐｏＥ）基因的分布。方法 利用聚合酶链式反应（ＰＣＲ）技术扩增ＡｐｏＥ基因含编码１１２位和１５８位氨基酸的片段，并用限制性片段长度多态性（ＲＦＬＰ）技术对ＡＣＩ患者和相应健康对照的ＡｐｏＥ基因进行分型，从而进行ＡＣＩ与ＡｐｏＥ等位基因多态性的关联分析。结果 ＡＣＩ患者中ＡｐｏＥ等位基因ε４占２８．３０％，明显高于正常人对照组的７．６４％，而等位基因ε３则占５７．５５％，低于正常人对照组的８４．１２％，均有极显著性差异（ｐ〈０．０１）。结论 ＰＣＲ－ＲＦＬＰ是一种快速有效的ＡｐｏＥ基因分型方法，ε４可能为ＡＣＩ的易感因子，而ε３则为保护因子。