冠心病患者E-选择素血清水平及其G98T、S128R基因多态性研究

目的　研究中国汉族人群E 选择素 (E selectin)基因第 2外显子G98T和第 4外显子S12 8R多态性与冠心病 (CHD)的相关性 ,以及对血清E selectin水平的影响。方法　采用聚合酶链反应 限制性片段长度多态性 (PCR RFLP)技术 ,检测 2 38例CHD患者和 199例健康人作对照者的E selectin基因多态性 ,同时采用酶联免疫吸附试验 (ELISA)检测CHD患者和对照者血清E selectin水平。结果　E selectin基因S12 8R基因型频率和等位基因频率在CHD组和对照组比较差异有显著性(P <0 0 5 ) ,基因型频率的相对风险分析发现 ,SR基因型携带者患冠心病的风险是SS基因型的 2 16 2倍 (OR =2 16 2 ,95 %CI:1 0 73～ 4 35 9) ,SR基因型携带者的E selectin血清水平显著高于SS基因型(4 2 9± 8 1比 35 7± 7 7,P <0 0 1)。E selectinG98T各基因型分布在CHD组和对照组之间比较差异无显著性 (P >0 0 5 ) ,但在心肌梗死组与心绞痛组间比较差异有显著性 (P <0 0 5 )。结论　E selectinS12 8R基因多态性与冠心病的发病有关联 ,并可影响血清E selectin水平 ,R等位基因可能是CHD发病的遗传易感基因 ;E selectin基因G98T多态性在冠心病发病中可能不起直接重要作用。     

No Association Between the Dopamine D2 Receptor Taq I A1 Allele and Earlier Age of Onset of Alcohol Dependence According to Different Specified Criteria

BACKGROUND: The presence of the A1 allele of the dopamine D2 receptor TaqI restriction fragment length polymorphism has been reported to be associated with an earlier age of onset of alcohol dependence as a marker for severity. METHODS: We tested this hypothesis with special regard to the definition of the age of onset of alcoholism in 243 patients with alcohol dependence, according to DSM-IV criteria assessed by the standardized interview Münchner Composite International Diagnostic Interview (M-CIDI), consecutively admitted for detoxification. Additionally, the Addiction Severity Index (ASI) was performed. The TaqIA polymorphism was amplified by polymerase chain reaction (PCR), and the PCR product was digested by the restriction enzyme TaqI. Patients were subsequently divided into an A1 (presence of at least one A1 allele, n = 88) and an A2 group (absence of an A1 allele, n = 155). The following criteria for different definitions of age of onset were used: (1) age of onset of the first occurring symptom necessary for the diagnosis of alcohol dependence according to M-CIDI; (2) age of onset of the last symptom of alcohol dependence according to M-CIDI; (3) age of onset of more than 3 drinking days per week on a regular basis according to ASI; (4) age of onset of more than 3 drinking days-of more than five drinks per drinking day-or at least one binge drinking episode per week on a regular basis according to ASI. RESULTS: The frequency of the A1 allele in our patient sample was 0.208. No statistically significant association between the A1 allele and the age of onset of alcoholism was found. The mean age of onset according to criterion 1 was 30.4 +/- 10.8 years for the A1 group and 30.2 +/- 10.2 years for the A2 group (p = 0.89); for criterion 2, it was 33.3 +/- 10.0 years for the A1 group and 33.9 +/- 10.2 years for the A2 group (p = 0.77); for criterion 3, it was 18.0 +/- 7.5 years for the A1 group and 18.1 +/- 6.1 years for the A2 group (p = 0.92); and for criterion 4, it was 22.3 +/- 9.7 years for the A1 group and 21.8 +/- 8.5 years for the A2 group (p = 0.76). CONCLUSIONS: No association was found between the A1 polymorphism and age at onset of alcohol dependence according to different specified criteria.     

国人脂蛋白脂肪酶基因突变的筛查

目的筛查天津地区脂蛋白脂肪酶基因突变情况,并探讨其对血脂水平的影响。方法利用聚合酶链反应—单链构象多态性分析技术对386例样本(血脂正常组278例,血脂异常组108例)的脂蛋白脂肪酶基因进行突变筛查,对可疑突变的扩增样品进行DNA序列测定。对于频率较高的多态性位点,引入限制性核酸内切酶位点利用聚合酶链反应限制片长多态性进行鉴定。结果在386例样本中,共检出4种突变,检出率为14.5%,其中1例为目前国内外未见报道的外显子3 Leu103→Leu同义突变杂合子,1例为目前亚洲首报的外显子5 Pro207→Leu突变杂合子,3例内含子3受位剪接点上游6 bp的C→T转换的突变杂合子,1例Ser447→stop突变纯合子,50例Ser447→stop突变杂合子。结论我国天津地区人群存在着广泛的脂蛋白脂肪酶基因变异,既具有与大多数国家相同的Ser447→stop多态性位点,也具有自身的特点。     

糖皮质激素受体遗传多态性与2型糖尿病相关性研究

目的 探讨糖皮质激素受体(GR)单核苷酸多态性与2型糖尿病(T2MD)易感性及人体体型的相关性.方法 采用病例-对照研究设计,从解放军总医院健康体检中心的体检患者中,募集40例T2MD患者和127例对照.结合三种不同的SNP位点选择方法,采用上海天昊生物科技有限公司的iMLDRTM多重SNP分型技术对入选SNP位点进行基因分型.采用非条件Logistic回归,校正年龄、性别、吸烟、饮酒后,分析基因型与T2MD易感性的关系.得到的阳性位点,进一步采用协方差分析,校正年龄、性别、吸烟、饮酒后,评价其与体重指数(BMI)和腰臀比(WHR)的相关性.结果 共选取14个SNP位点,其中rs10052957突变型在病例组中频率为零,故未纳入统计分析.所有的13个SNP位点在病例和对照组中的基因分型均符合Hardy-Weinberg平衡.rs9324924 TT基因型(OR [95％CI]=3.12[1.06 ～9.17],P=0.039)和rs9324921 AA基因型(OR [95％CI]=14.92[1.39～160.60],P=0.026)发生T2DM的风险较野生型增高,且两基因型的BMI[P=0.023 (rs9324924);P=0.002(rs9324921)]、WHR[P=0.033 (rs9324924);P=0.003(rs9324921)]也较野生型明显增高.结论 在本研究中,GR基因rs9324924、rs9324921与T2DM易感性和体型有关,其中纯和突变型T2DM发病风险明显增加,且更具有肥胖倾向.     

中国人群缺血性脑卒中相关基因的多态性分析

目的 探讨中国人缺血性脑卒中与凝血因子、细胞粘附分子、血小板膜糖蛋白、血浆凝血酶原激活物抑制剂1以及肿瘤坏死因子基因多态性的关系。方法 利用PCR技术和分子杂交技术对1122例缺血性脑卒中患者进行10个基因17个多态性位点的检测和分析，并与1123例非卒中对照进行比较。结果 缺血性脑卒中患者肿瘤坏死因子βthr26asn多态性分布与对照组相比具有显著差异。其他基因多态性的基因型频率和等位基因频率与对照组相比无明显差异。结论 肿瘤坏死因子βthr26asn多态性分布与中国人缺血性脑卒中的发生具有关联性，提示TNFβ thr26asn多态性可能是中国人群缺血性脑卒中发生的一个遗传学危险因素。     

Oxidized to non-oxidized lipoprotein ratios are associated with arteriosclerosis and the metabolic syndrome in diabetic patients

Background and aimType 2 diabetic patients have a greater prevalence of the metabolic syndrome, oxidative stress and accelerated atherosclerosis, compared to non-diabetics. We examined the association between biomarkers of lipid peroxidation and the presence of atherosclerosis and the metabolic syndrome in diabetic patients.Methods and resultsWe studied oxidized LDL (OxLDL), OxLDL/LDL, OxLDL/HDL, lipoperoxides, autoantibodies against OxLDL (OxLDL-Ab), diene formation of LDL (lag phase), vitamin E, vitamin E/cholesterol and PON1 polymorphisms (−108C > T, 55T > A, and 192A > G) in 166 non-smoking type 2 diabetic patients, 119 fulfilling the criteria for the metabolic syndrome, 73 with atherosclerosis and 93 without atherosclerosis. Patients with macrovascular disease had higher values of OxLDL/LDL (11%; P = 0.016), OxLDL/HDL (18%; P = 0.024) and OxLDL-Ab (12%; P = 0.046). OxLDL/LDL and OxLDL/HDL were correlated with the number of components of the metabolic syndrome (P < 0.001). PON1 polymorphisms were not associated to LDL oxidation markers, only PON1 (−108TT) was weakly associated with higher OxLDL-Ab concentrations (22%; P = 0.040) in patients with atherosclerosis.ConclusionOxLDL/LDL, OxLDL/HDL and OxLDL-Ab are the most useful clinical parameters of lipoprotein oxidation for discriminating the presence of macrovascular disease in diabetic patients. The presence of the metabolic syndrome in these patients is also associated with an increase in the oxidized lipoprotein ratios.     

Relationship between metabolic enzyme polymorphism and colorectal cancer

AIM: To clarify the influence of genetic polymorphisms on colorectal cancer. METHODS: The results of 42 related studies from 1990 to 2001 were analyzed by meta-analysis. Mantel-Haenzel fixed-effect model or Dersimonian-Laird random-effect model and ReviewManager 4.1 statistical program were applied in processing the data. RESULTS: Meta analysis of these studies showed that GSTT1 deletion (pooled OR= 1.42), N-acetyltransferase 2 (NAT2)-rapid acetylator phenotype and genotye (pooled OR = 1.08) and NAT2-rapid acetylator phenotype (pooled OR = 1.15) had a significantly increased risk for colorectal cancer (P<0.05), other genotypes like GSTM1 deletion, GSTP1 1le105Val, NAT1*10, NAT2-rapid acetylator genotype CYP1A1 Lle462Val, CYP1A1 MspI*C, MTHFR C677T and MTR A2759G had no significant relationship with colorectal cancer (P>0.05). CONCLUSION: Risks for colorectal cancer are significantly associated with the genetic polymorphisms of GSTT1 deletion, NAT2-rapid acetylator phenotype and genotye and NAT2-rapid acetylator phenotype.     

间质金属蛋白酶基因多态性与中心性肥胖在非酒精性脂肪肝病中交互作用研究

目的 探讨间质金属蛋白酶-9(MMP-9)-1562C/T(rs3918242)以及MMP-2-1306C/T(rs243865)位点单核苷酸多态性(SNP)与非酒精性脂肪肝(NAFLD)遗传易感性以及与中心性肥胖交互作用。方法 对545例NAFLD患者和636例正常对照,采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析rs24386以及rs3918242基因型、非条件logistic分析各基因型与脂肪肝发病易感性关系,利用非条件logistic分析和广义多因子降维(GMDR)法分析rs3918242、rs243865与中心性肥胖的交互作用。结果 MMP-9 rs3918242位点T基因携带者(TT/CT)与非T基因携带者(CC)的NAFLD罹患风险明显增加(OR=1.67,95%CI:1.32～2.12,P=0.001;调整OR=1.65,95%CI:1.31～2.01,P=0.008);而MMP-2 rs243865位点T基因携带者(TT/CT)与非T基因携带者(CC)的NAFLD罹患风险明显降低(OR=0.68,95%CI:0.53～0.86,P=0.001;调整OR=0.66,95%CI:0.49～0.90,P=0.007)。广义多因子降维法分析结果显示,rs3918242与中心性肥胖在NAFLD发病中存在交互作用(P=0.001)。利用非条件logistic校正年龄、性别、腰围、BMI、LDL-C、HDL-C、FPG、胰岛素抵抗指数后,分析显示,携带rs3918242 TT/CT基因型中心性肥胖个体罹患NAFLD的风险高于携带CC基因非吸烟个体(OR=4.50,95%CI:2.78～7.17,P=0.007)。结论 MMP-9基因的rs3918242以及MMP-2基因的rs243865与NAFLD患病罹患风险紧密相关,rs3918242与中心性肥胖在NAFLD发病中具有协同效应。     

四川盆地结核分枝杆菌群体遗传学特征研究

目的 探讨四川盆地(重庆、四川地区)流行的结核分枝杆菌(MTB)群体遗传学特征。方法 对413株源自四川盆地的MTB进行长序列多态性(LSP)谱系鉴定, 采用χ²检验分析不同谱系MTB在人群中的分布差异。对菌株进行15位点数目可变串联重复序列基因分型, 评价各位点的分辨力。构建N-J树分析其系统进化;构建最小跨度树以模拟群体菌株的遗传结构;采用分子方差分析不同谱系MTB的群体间遗传分化;采用贝叶斯模型计算菌株最近共祖年代。结果 通过LSP可将413株MTB分为两大谱系, 其中北京谱系占56.2%(232/413), 欧美谱系占43.8%(181/413)。两谱系MTB在人群中的分布(性别、年龄、民族以及菌株耐药性)差异无统计学意义(P>0.05)。北京谱系MTB的N-J树呈放射状分布, 最小跨度树中有72.4%(168/232)的菌株被划分到同一“克隆复合群”;欧美谱系MTB的N-J树呈枝状分布, 最小跨度树中呈现出多个“克隆复合群”。北京谱系MTB在该地区有显著的群体间遗传分化(F_ST=0.018 91, P<0.05), 而欧美谱系MTB群体间遗传分化不显著(F_ST=0.005 19, P>0.05)。欧美谱系MTB中最大菌株复合群的最近共祖年代为723(95%CI:517～946)年。结论 北京谱系和欧美谱系MTB在四川盆地以“互相对抗”形式流行;两谱系MTB的群体间遗传分化存在差异;欧美谱系MTB的侵入可能与一次历史事件(约720年前的战争)有关。     

载脂蛋白CⅢ基因多态性对不同体质量指数青少年血脂水平的影响

目的 探讨载脂蛋白CⅢ基因(APOC3) Sst Ⅰ和-482C＞T多态性与不同体质量指数(BMI)健康青少年血脂水平的相关性.方法 根据BMI将723例青少年按四分位数分为4组,从低到高依次为1组[BMI=(17.80±0.75) kg/m2,n=180]、2组[BMI=(19.39±0.32) kg/m2,n=182]、3组[BMI=(20.68±0.43) kg/m2,n=181]和4组[BMI=(23.40±2.05) kg/m2,n=180].抽取空腹静脉血5 mL,测定血脂,提取基因组DNA并采用PCR-RFLP法对APOC3 Sst Ⅰ和-482C＞T多态性位点进行分型.结果 随着BMI增加,身高和高密度脂蛋白胆固醇降低(P＜0.001);体质量、腰围、臀围、腰臀比、甘油三酯(TG)、总胆固醇和低密度脂蛋白胆固醇升高(P＜0.001).SstⅠ多态性不同基因型青少年的血脂水平在1组、2组和3组中差异无统计学意义;在第4组中,血浆TG水平在不同基因型之间差异有统计学意义(P=0.022),S2等位基因携带者的TG水平高于S1S1基因型青少年.-482C＞T多态性不同基因型青少年的血脂水平在各组中差异无统计学意义.结论 在健康青少年中,APOC3 SstⅠ多态性S2等位基因对血浆TG的升高作用与BMI有关,降低体质量或可改善S2等位基因对血浆TG的增高作用.