尿激酶型纤溶酶原激活剂和脑啡肽酶基因多态性与阿尔茨海默病的相关性研究

目的探讨尿激酶型纤溶酶原激活剂（PLAU）和脑啡肽酶（NEP）基因单核苷酸多态性与散发性阿尔茨海默病（SAD）的相关性。方法提取138例SAD患者和125例正常志愿者的静脉血基因组DNA，应用多聚酶链式反应扩增目的基因片段，应用聚合酶链式反应一限制性片段长度多态性的方法进行基因分型。结果比较PLAU基因rs2227564位点的三种基因型分别与NEP基因rs3736187位点的三种基因型组合起来组成八种基因型频率在SAD组与对照组中的分布，结果显示有显著性差异（x^2=16．953，P=0．018）。SAD组TTCT基因型频率降低，TTCT缺失基因型频率增高，与对照组比较有显著性差异（x^2=6．464，P=0．011）。结论PLAU和NEP复合基因的多态性与SAD的发病具有相关性，TTCT基因型可能是SAD的保护基因型。     

GSK3B基因启动子区多态性与中国北方汉族人群阿尔茨海默病的相关分析

目的研究中国北方汉族人群中糖原合成酶激酶38基因（GSK3B）启动子区rs334558位点基因多态性与阿尔茨海默病（AD）易感性的相关性。方法采用直接测序的方法,对403例AD病例及369名对照外周血DNA的GSK3B基因多态位点rs334558进行基因分型。结果AD组与对照组rs334558位点等位基因和基因型分布相似,等位基因T的频率在AD组和对照组分别为38．8％和37．9％,差异无统计学意义（y。一0．130,P〉0．05）。按照性别或者是否携带AopF~4等位基因分别进行分层分析,发现AD组和对照组之间等位基因频率和基因型分布的差异无统计学意义（,分别为0．331,0．565;P〉0．05）。结论GSK3B基因启动子区多态性位点rs334558可能与中国汉族人群AD发病无关。     

三磷酸腺苷结合盒转运子A1基因多态性与散发性阿尔茨海默病的关系

目的 探讨三磷酸腺苷结合盒转运子A1（ATP—binding cassette transporter 1，ABCA1）基因第6外显子D→A（R219K）多态性位点与散发性阿尔茨海默病（sporadic Alzheimer disease，SAD）易患性的关系。方法 采用病例．对照研究方法，利用聚合酶链反应．限制性片段长度多态性（PCR—RFLP）技术对168例SAD患者和215名健康对照的ABCA1基因多态性进行检测，比较不同基因型与阿尔茨海默病（AD）发病风险之间的关系。结果 SAD组ABCA1基因第6外显子G—A多态位点A等位基因频率明显低于对照组（37．8％ vs 48．1％，）（X^2=8．204，P=0．004）；SAD组AA基因型频率也明显低于对照组（14．3％ vs 22．8％，）（X^2=8．230，P=0．016）。Logistic回归分析表明，校正年龄、性别和ApoEe4等位基因的影响后，携带A等位基因者（G／A＋A／A基因型）比携带GG基因型者AD发病风险降低43．0％（OR 0．57，95％CI 0．36—0．91，P=0．019），而AA纯合子比携带GG基因型者AD发病风险降低60．0％（OR 0．40，95％ CI 0．21—0．77，P：0．006）。结论 ABCA1基因第6外显子D—A多态性与SAD相关，携带A等位基因或者AA基因型对SAD发病可能有一定的保护作用。     

CLU基因多态性与新疆哈萨克族及汉族阿尔茨海默病的相关性研究

目的探讨聚集素(clusterin,CLU)基因rs11136000位点及rs9331888位点多态性与新疆哈萨克族(简称哈族)及汉族散发性阿尔茨海默病(Alzheimer’s disease,SAD)相关性。方法运用病例对照研究,采用Kas P PCR技术和基因测序法测定CLU rs11136000及rs9331888位点的基因型及等位基因。结果 (1) CLU基因rs11136000位点基因型及等位基因分布在SAD及正常对照组差异有统计学意义(P 0. 05)。哈族SAD组CLU基因rs11136000位点T等位基因及TT基因型频率显著低于对照组(χ~2=8. 809,P=0. 003;χ~2=8. 242,P=0. 016)。携带T等位基因者(TT+TG基因型)相比携带GG基因型者AD发病风险降低63. 9%(OR=0. 361,P=0. 007)。汉族SAD CLU基因rs11136000位点基因型及等位基因与对照组之间差异均无统计学意义(P 0. 05)。(2) CLU rs9331888位点等位基因(C、G)及基因型(CC、CG、GG)频率差异无统计学意义(P 0. 05)。(3) rs9331888、rs11136000两位点存在连锁不平衡(D’=0. 764),单体型分析显示有C-C、C-G、T-G 3种单体型,频率分布差异无统计学意义(P 0. 05)。结论 CLU基因rs11136000位点多态性与新疆哈族AD发生可能有关,携带T等位基因对降低AD发病可能有一定的保护作用; CLU基因9331888位点可能与新疆SAD的发生无相关性。     

环指蛋白213基因多态性与中国汉族成人型烟雾病遗传易患性的相关性

目的 探讨环指蛋白213(RNF213)基因rs112735431和rs138130613两位点多态性与中国汉族成人型烟雾病的遗传易患性的关系.方法 从南京卒中注册系统中提取2010年12月至2011年10月经脑血管造影明确诊断的64例成年型烟雾病患者,同时选取96名性别和年龄与烟雾病患者相匹配的健康人作为对照.通过改进的多重连接酶检测反应技术分析RNF213基因rs112735431和rs138130613位点的多态性,对各位点基因型、等位基因型频率进行比较分析.结果 病例组中rs112735431位点GA+AA基因型频率为10.94％(7/64)、GG基因型频率为89.06％(57/64),等位基因A频率为6.25％ (8/128)、等位基因G频率为93.75％ (120/128)；对照组分别为1.04％(1/96)、98.96％(95/96),0.52％ (1/192)、99.48％ (191/192),两组间差异具有统计学意义(OR=11.67,95％ CI 1.40 ～97.28,P =0.007;OR=12.73,95％ CI 1.57 ～ 103.09,P=0.003).rs138130613位点的基因型和等位基因频率在两组间差异无统计学意义.结论 RNF213基因rs112735431位点的多态性可能是中国汉族成人型烟雾病患者的易患因子.     

卷曲蛋白6基因多态性与中国北方汉族儿童神经管缺陷的相关性

目的 研究中国北方汉族儿童卷曲蛋白6基因编码区单核苷酸多态性(singlenucleotide polymorphisms,SNPs)与神经管缺陷(neural tube defects,NTDs)发生的相关性.方法 采用PCR扩增和测序的方法对135例NTDs患儿和135例对照者卷曲蛋白6基因编码区3个错义单核苷酸多态位点(rs827528,rs3808553,rs12549394)进行基因分型及统计学分析.结果 rs3808553等位基因T和基因型TT在病例组中的频率显著高于对照组,T等位基因和TT基因型儿童发生NTDs的危险性分别是G等位基因和GG基因型的1.575倍(OR=1.575,95％CI1.112 ～2.230,P=0.010)和2.811倍(OR =2.811,95％CI 1.325～5.967,P=0.023);其余2个多态位点在两组间等位基因与基因型分布差异不具有统计学意义.3个SNPs位点间的单体型A-G-C在病例-对照组间分布具有统计学意义(OR =0.560,95％CI0.378～0.830,P=0.004),而单体型A-T-C在病例-对照组间分布也具有统计学意义(OR=1.670,95％CI 1.126 ～2.475,P=0.011).结论 中国北方汉族儿童中卷曲蛋白6基因rs3808553位点多态性与NTDs发生具有明显相关性,基因型TT使NTDs发生的危险度增加,而rs827528和rs 12549394位点多态性与NTDs发生无明显相关性.     

脑啡肽酶基因多态性与散发性阿尔茨海默病的关系研究

目的探讨脑啡肽酶(neprilysin,NEP)基因单核苷酸多态性与中国北方汉族散发性阿尔茨海默病(sporadic Alzheimer’s disease,SAD)的关系。方法临床确诊的99例中国北方汉族SAD患者及109例正常对照,提取外周血基因组DNA,聚合酶链反应-限制性片段长度多态性结合DNA直接测序法确定NEP基因rs989692位点及rs6776185位点基因型,分析上述两个位点单核苷酸多态性与AD的关系。结果 AD组和正常对照组NEP基因rs989692位点各等位基因频率及基因型分布无显著性差异(P>0.05);AD组NEP基因rs6776185位点A等位基因频率显著高于正常对照组(88.9%vs 81.2%,P=0.029),AA基因型频率显著高于正常对照组(80.8%vs 67.0%,P=0.024);携带A等位基因者,发生AD的风险是不携带A等位基因者的1.85倍(OR=1.85,95%CI 1.07~3.20);经载脂蛋白E基因(apolipoprotein E,Apo E)ε4等位基因及年龄分层比较,携带ε4基因及年龄<75岁组,AD组A等位基因及AA基因型分布频率仍明显高于正常对照组(P<0.05)。结论 NEP基因rs6776185位点A等位基因和AA基因型可能是中国北方汉族人群SAD的危险因素,可使AD发病年龄提前,并与Apo Eε4等位基因可能具有协同作用。     

CAMSAP1L1基因多态性与我国中部地区人群癫痫的相关性分析

目的 探讨我国中部地区汉族人群中CAMSAP1L1基因两个SNP位点rs6660197和rs2292096的多态性与癫痫遗传易感性的关系.方法 采取病例对照研究方法,分别选取157例癫痫患者,其中包括122例良性癫痫伴中央颞区棘波（BECT）和35例难治性癫痫（RE）患儿;选取160例正常体检儿童作为研究对象.利用PCR-RFLP的方法测定两个SNP位点多态性分布,并进行统计分析.结果 在所有患者中SNP位点（rs6660197）的基因型（CC,CT,TT）频率和等位基因C频率与对照组比较差异均有统计学意义（P＜0.05）;SNP位点（rs2292096）的基因型（AA,AG,GG）频率两组比较差异无统计意义（P＞0.05）.SNP位点（rs6660197）与我国中部地区汉族人群BECT的易感性相关（P=0.040）,CC为风险基因型,C等位基因为风险因子,与对照组比较OR =1.584,95％ CI：1.046～2.398,P=0.029.RE患者SNP位点（rs2292096）的基因型与对照组比较差异有统计学意义（P=0.028）,A等位基因为风险因子（OR=2.431,95％CI：1.265～4.134,P=0.010）,等位基因频率明显高于对照组（P=0.010）.结论 CAMSAP1L1基因SNP位点（rs6660197）与BECT的易感性相关,而SNP位点（rs2292096）与RE的易感性相关.     

乙二醛酶Ⅰ基因rs1049346 G/A多态性与耐药性癫痫的相关性

目的 探讨乙二醛酶Ⅰ （Glo Ⅰ）基因rs1049346 G/A多态性和耐药性癫痫的相关性.方法 收集67例汉族耐药性癫痫患者和69例汉族非耐药性癫痫患者.采用SNaPshot方法检测患者外周血Glo Ⅰ基因rs1049346 G/A多态性.结果 耐药组GG、GA、AA基因型分别占6.0％,49.3％,44.7％,非耐药组分别占7.2％,53.6％,39.1％,总体差异无统计学意义（χ^2=0.46,P=0.79）.耐药组等位基因G、A频率分别为30.6％,69.4％,非耐药组患者分别为34.1％,65.9％,差异也无统计学意义（OR =0.85,95％ CI 0.51-1.42,χ^2=0.37,P=0.54）.结论 Glo Ⅰ基因rs1049346 G/A多态与汉族癫痫耐药可能无相关性.     

中国汉族人群磷酸酶与张力蛋白同源物基因多态性与早发性精神分裂症的关联研究

目的：探讨中国汉族人群磷酸酶与张力蛋白同源物（phosphataseandtensinhomolog,PTEN）基因多态性与早发性精神分裂症（EOS）的关系。方法：纳入270例EOS患者和447名健康对照,用SNaPshot技术对PTEN的标签SNP进行基因分型,比较其等位基因、基因型、单体型分布频率在两组间有无差异。结果：rs2299941的等位基因分布在两组间存在边缘统计学差异（X2=4．454,P：0．035,校正P=0．175）,GG基因型在隐性遗传模式下显著降低EOS的发生风险（OR=0．51,95％CI=0．31～0．85,P=0．007）。rs17562384的CC基因型在隐性遗传模式下显著增加EOS的发生风险（OR：2．23,95％CI=1．01～4．91,P=0．047）。单体型GTr（rs2299941、rsl7562384、rs532678）的分布频率在患者组与对照组间存在边缘统计学差异（O．308VS0．364;x2=4．677,P=0．031,校正P=0．057）。结论：中国汉族人群PTEN基因多态性与EOS易感性有关。     

Biochemical Study of Adrenoleukodystrophy (ALD)

Abstract: Adrenoleukodystrophy (ALD) is an x-linked hereditary neurological disorder characterized by the accumulation of cholesterol ester with long chain fatty acids in the brain and adrenal gland. We examined cholesterol ester metabolism for the postmortem brain tissues of ALD patients, using cholesterol ester with short and long chain fatty acids as the substrate for hydrlyzing enzyme, as well as short and long chain fatty acids for synthesizing enzyme.
No enzyme abnormality was found. However, there was a discrepancy between hydrolytic and synthetic activities with short or long chain fatty acids. The findings suggest that the accumulation of cholesterol ester with long chain fatty acids in ALD brain is not due to enzyme abnormalities, but is a secondary phenomenon which comes from abnormal fatty acid metabolism causing a high concentration of long chain fatty acids.     

Distribution of cholesterol 24-hydroxylase in the monkey brain

Objective

Cholesterol 24-hydroxylase catalyzes the conversion of cholesterol to 24-hydroxycholesterol, which is a major pathway for cholesterol elimination from the brain, since 24-hydroxycholesterol can readily cross the blood brain barrier. The present study aimed to elucidate the distribution of cholesterol 24-hydroxylase in the monkey brain.

Methods

The distribution of cholesterol 24-hydroxylase in the monkey brain was examined using Western blot and immunohistochemistry methods, and was observed under light microscopy and electron microscopy.

Results

High levels of cholesterol 24-hydroxylase were observed in projection neurons and neuropil in structures derived from telencephalon, including the cerebral neocortex, hippocampus, amygdala, nucleus basalis of Meynert, and striatum. Electron microscopy revealed that the enzyme was localized in the axon terminals. One the other hand, cholesterol 24-hydroxylase was expressed at a lower level in the thalamus, globus pallidus and brainstem.

Conclusion

The high level of cholesterol 24-hydroxylase in the telencephalon possibly reflects a high rate of cholesterol turnover in this part of brain.     

THE EFFECT OF CHOLESTEROL OXIDATION PRODUCTS ON HUMAN PLATELET AGGREGATION

The cholesterol oxidation products (oxysterols) cholest-3,5-diene-7-one, cholestan-5, 6-epoxy-3β-ol (cholesterol 5-epoxide), cholestan-5β,6β-epoxy-3β-ol (cholesterol 5β-epoxide), cholest-5-ene-3β-ol-7-one (7-ketocholesterol), cholest-5-ene-3β,7-diol (7-hydroxycholesterol), cholestan-3β,5,6β-triol (choestane triol), and cholest-5-ene-3β,26-diol (27-hydroxycholesterol) potentiated platelet aggregation and increased thromboxane A₂ formation in platelets challenged with thrombin, ADP or collagen. These effects were observed at oxysterol concentrations in the range 5–100 μM. Cholesterol 5β-epoxide and 7-ketocholesterol increased the mobilization of ³H-arachidonic acid from prelabelled platelet phospholipids in response to thrombin and collagen.     

Serum cholesterol levels and the risk of multiple system atrophy: A case‐control study

Cholesterol in brain membranes may modulate the conformational state and accumulation of α‐synuclein in α‐synucleinopathies.We examined the association between serum cholesterol and the risk of multiple system atrophy (MSA), one of the α‐synucleinopathies. We enrolled 142 patients with probable MSA from two tertiary referral hospitals and 155 age‐ and gender‐matched healthy people with no neurological disease. The levels of total cholesterol, low‐density lipoprotein cholesterol (LDL‐C), and high‐density lipoprotein cholesterol (HDL‐C) were significantly lower in MSA patients than in controls (total cholesterol: 172.7 vs. 196.3 mg/dL, P < 0.001; LDL‐C: 104.0 vs. 115.3 mg/dL, P = 0.001; HDL‐C: 47.3 vs. 54.2 mg/dL, P < 0.001). After adjusting for age, gender, use of cholesterol‐lowering drugs, and histories of hypertension, diabetes mellitus, and smoking, the odds ratios was 5.9 (95% CI = 2.3–11.5, P < 0.001) for MSA patients in the lowest quartile of total cholesterol and 2.6 (95% CI = 1.2–5.5, P = 0.016) for those in the lowest quartile of HDL‐C, compared with the highest quartiles. Levels of serum cholesterol did not significantly correlate with disease duration or severity. Our data suggest that lower levels of total cholesterol and HDL may be associated with an increased risk of MSA. © 2009 Movement Disorder Society     

血清胆固醇与脑胶质瘤的关系

对37例脑胶质瘤病人及42例住院对照组病人血清脂类及脂蛋白胆固醇进行了分析.结果显示,脑胶质瘤病人血清甘油三酯和总胆固醇含量均明显高于对照组,其中女性病人升高尤为显著.表明血清胆固醇及甘油三酯含量升高与脑胶质瘤的发生、发展有关.     

非高密度脂蛋白胆固醇水平与周围动脉疾病的相关性研究

目的 评估不同非高密度脂蛋白胆固醇（non-high-density lipoprotein cholesterol，non-HDL-C）水平与周 围动脉疾病（peripheral artery disease，PAD）的关系。 方法 本研究纳入2010年6月-2011年6月年龄≥40岁、既往无心脑血管病史的社区人群，收集人口 学信息、血管相关危险因素、生化相关检查等资料。PAD定义为踝臂指数＜0.9；non-HDL-C水平分为： 正常＜4.1 mmol/L，边缘升高4.1～4.9 mmol/L，升高≥4.9 mmol/L；采用单因素和多因素logistic回归分 析non-HDL-C水平与PAD的相关性。 结果 共纳入5132例受试者，平均年龄55.13±11.80岁，男性3214例（60.07%），平均non-HDL-C水平 为3.42±1.00 mmol/L，其中PAD患病率为3.39%（174/5132）。PAD受试者non-HDL-C水平高于无PAD受 试者，但差异无统计学意义（3.51±1.03 mmol/L vs 3.42±1.00 mmol/L，P＞0.05）。进一步多因素分析 结果显示，边缘升高（OR 1.23，95%CI 0.78～1.93，P ＞0.05）和升高non-HDL-C水平（OR 1.24，95%CI 0.60～2.55，P＞0.05）与PAD患病风险无关。 结论 本研究中未发现non-HDL-C与PAD的相关性。     

Plasma HDL cholesterol in epileptics with elevated triglyceride and cholesterol

Due to the metabolic changes induced, e.g. in the liver by anti-epileptic drugs, the significance of high serum triglyceride and cholesterol in epileptics was studied and the plasma HDL cholesterol level was compared in 190 epileptic patients with elevated or normal triglyceride and cholesterol, with the corresponding values in 43 healthy subjects. One-third of the epileptic patients showed elevated plasma HDL cholesterol levels. Female epileptics had higher plasma HDL cholesterol than the normolipidemic healthy subjects. Epileptics with elevated triglyceride or a combination of elevated triglyceride and cholesterol had a lower plasma HDL cholesterol level than normolipidemic patients with epilepsy. HDL cholesterol level in epileptics with high serum cholesterol did not diverge from the level in epileptics with normal serum triglyceride and cholesterol. The results show significant differences of plasma HDL cholesterol between epileptic patients and normolipidemic healthy controls on one hand, and between epileptics with altered and epileptics with normal serum lipid levels on the other. The findings suggest that the increase of plasma HDL cholesterol level in epileptics undergoing anticonvulsant treatment is influenced by endogenous triglyceride metabolism.     

Preliminary report on effects of oxcarbazepine-treatment on serum lipid levels in children

The aim of the present study was to assess serum lipid levels before and after treatment with oxcarbazepine (OXC) in children with epilepsy. We measured total cholesterol (TC), triglycerides (TGs) and high-density lipoprotein cholesterol (HDL-C) in 28 patients whereas only TC levels in 11 patients, during baseline period and at 3 months after the beginning of therapy with OXC. During baseline period, median values were: 4.38 mmol/l (IQR = 4.12–5.03) for TC levels, 1.72 mmol/l (IQR = 1.42–2.01) for HDL-C levels and 1.54 mmol/l (IQR = 1.29–1.96) for TGs levels. At 3 months, median values were: 4.38 mmol/l (4.10–4.95) for TC levels ( P  < 0.05), 1.57 mmol/l (1.34–1.93) for HDL-C levels ( P  < 0.005) and 1.8 mmol/l (1.23–2.34) for TGs levels ( P  < 0.05). Median serum lipid levels remained in the normal range, despite an increasing-trend at 3 months of treatment with OXC. Further studies are necessary to confirm these results.     

LDL-C/HDL-C ratio and risk of all-cause mortality in patients with intracerebral hemorrhage

Background: The low-density lipoprotein cholesterol/high-density lipoprotein cholesterol (LDL-C/HDL-C) ratio has been recognized as a strong risk predictor of cardiovascular diseases. However, the association between the LDL-C/HDL-C ratio and the prognosis of acute intracranial hemorrhage (ICH) is unclear. Thus, we prospectively investigated whether a low LDL-C/HDL-C ratio could predict all-cause mortality and whether LDL-C/HDL-C ratio is superior to traditional lipid profiles in predicting mortality among Chinese patients with acute ICH.

Methods: A prospective cohort study of 356 patients with acute ICH was conducted, and the mean follow-up time point was 80.4 days. Participants were divided into four categories based on LDL-C/HDL-C ratio quartiles. Three-month outcomes were evaluated by in-person or telephone interviews with patients or their family members. The end point was three-month mortality from all causes.

Results: Forty-seven deaths from all causes were documented. The multivariate analysis found that LDL-C/HDL-C ratio [hazard ratio (HR) = 0.49, p = 0.008] and LDL-C (HR = 0.27, p = 0.044) were significantly associated with all-cause mortality. The Kaplan–Meier curves show that patients in the lowest quartiles had the highest cumulative incidence rates (log-rank p = 0.027). After adjusting for covariates, a low LDL-C/HDL-C ratio was associated with a 3.55-fold increase in the risk of all-cause mortality (HR, 3.55 [95% confidence interval, 1.04–12.14]; P-trend = 0.011) when the highest and lowest quartiles were compared. The C-statistic of the LDL-C/HDL-C ratio was significantly larger than other traditional lipid profiles (all p < 0.05).

Conclusions: A low LDL-C/HDL-C ratio was independently associated with an increased risk of all-cause mortality at three months in patients with ICH. Moreover, the LDL-C/HDL-C ratio appeared to be a best lipid predictor of all-cause mortality than traditional lipid profiles.     

抑郁症患者的血糖、血脂水平及其与症状关系的对照研究

目的了解抑郁症患者糖脂代谢的情况及其与精神症状的关系。方法以HAMD17和HAMA评定92例近期未服用精神药物的抑郁症患者的精神症状,了解他们简易体质参数、测定其空腹血糖和血脂,并与60例健康者组成的对照组进行比较。结果抑郁症组的甘油三酯(TG)、空腹血糖(FBS)值显著高于对照组(P＜0．001),而高密度脂蛋白胆固醇(LDL—ch)、载脂蛋白A1(ApoA1)值显著低于对照组(P＜0．01)；血浆总胆固醇(TC)、高密度脂蛋白胆固醇(HDL—ch)和载脂蛋白B(ApoB)两组之间无显著性差异(P＞0．05)；相关分析发现,抑郁症患者的HAMA总分、精神性焦虑因子分以及躯体性焦虑因子分与TG水平呈正相关(P＜0．01或P＜0．05)。结论抑郁症患者存在一定的糖脂代谢异常,临床医师应该对抑郁症患者的血糖、血脂进行监测,以便早期发现,早期治疗。