PC-1基因多态性与2型糖尿病及胰岛素抵抗的相关性

目的 探讨浆细胞膜精蛋白PC-1基因多态性与胰岛素抵抗（IR）特征和2型糖尿病（DM）的关系。方法 运用聚合酶链反应．限制性片段长度多态性（PCR-RFLP）技术对深圳市133例2型DM患者和108例非DM对照人群的PC-1基因第四外显子K121Q多态性进行分析，并对2型DM组不同基因型间临床及生化指标进行比较。结果 2型DM组与非DM对照组比较，PC-1基因型频率和等位基因频率分布差别均无统计学意义；2型DM组携带Q等位基因者空腹血糖、甘油三酯及空腹血C肽水平显著高于携带K等位基因者。结论 Pc-1基因K121Q多态性与2型DM患者IR表型相关，但与2型DM的发生无明显关联。     

脂联素基因多态性与新疆地区汉族2型糖尿病的相关性研究

目的研究脂联素(APN)基因45T/G单核苷酸多态性(SNPs)与新疆地区汉族人2型糖尿病(T2DM)的相关性。方法采用聚合酶链反应-限制性内切酶片段长度多态性技术(PCR-RFLP),比较新疆地区汉族人正常糖耐量组(NGT)和T2DM组APNSNP45基因型与等位基因分布频率差异;比较相同人群不同基因型和不同人群相同基因型T2DM相关体测与生化指标的差异。结果 T2DM组APNSNP45TG+GG基因型及G等位基因分布频率均高于NGT组(P﹤0.005);NGT组TG+GG基因型者血清甘油三酯(TG)、总胆固醇(CH)和低密度脂蛋白(LDL)水平显著高于TT基因型者(P﹤0.005),相同基因型人群之间,T2DM组收缩压(SBP),体重指数(BMI),腰臀比(WHR),空腹血糖(FBG),胰岛素抵抗指数(LOG(HOMA-IR)),TG,CH及LDL均高于NGT组(P﹤0.05);胰岛β细胞功能指数(LOG(HOMA-β))和高密度脂蛋白(HDL)水平均低于NGT组(P﹤0.005)。结论 APNSNP45T/G多态位点与新疆地区汉族T2DM相关,携G等位基因者发生T2DM的可能性增加,且G等位基因与汉族血脂代谢异常及胰岛素抵抗有关。     

2型糖尿病中老年住院患者轻度认知障碍与载脂蛋白E基因多态性的关系

目的探讨2型糖尿病（T2DM）中老年住院患者轻度认知功能障碍（MCI）与载脂蛋白E（ApoE）基因多态性的关系。方法采用蒙特利尔认知评估（MoCA）量表和日常生活能力评定（ADL）量表对研究对象的认知功能进行评定,共纳入T2DM患者218例,其中合并MCI患者114例（T2DM合并MCI组）,认知功能正常患者104例,以糖耐量正常、认知功能正常的119例健康者为正常对照组。采用等位基因特异性多重（multi—ARMS）聚合酶链反应（PCR）技术检测研究对象的ApoE基因型。分析各组等位基因及基因型频率分布特点并比较MoCA评分结果。结果T2DM合并MCI患者的E4／X基因型（包括基因型e3／4和e4／4）频率（37．0％）、￡4等位基因频率（24．6％）均高于患T2DM且认知功能正常患者（分别为19．8％、12．0％）及正常对照组（分别为16．4％、10．1％）,差异均有统计学意义（P〈0．05）。携带84等位基因的T2DM患者MoCA测试中视空间与执行能力、注意力与计算力、抽象和定向评分均低于未携带￡4等位基因的T2DM患者,差异均有统计学意义（P〈0.05）。结论ApoE基因多态性与T2DM合并MCI有关,S4等位基因可能是T2DM合并MCI的危险因素。     

2型糖尿病患者血清脂蛋白比值与胰岛素抵抗的相关性研究

目的探讨2型糖尿病（T2DM）患者血清脂蛋白比值与胰岛素抵抗的相关性。方法随机选取62例T2DM患者（T2DM组）及60例健康者（对照组）,分别测定空腹血糖（FBG）、空腹胰岛素（FINS）、甘油三酯（TG）、总胆固醇（TC）、高密度脂蛋白胆固醇（HDL—C）、低密度脂蛋白胆固醇（LDL—C）等,计算TG／HDL-C、TC／HDL—C及LDL．C／HDL—C比值,采用稳态模型（HOMA）计算胰岛素抵抗指数（HOMA—IR）,并作相关统计学分析。结果T2DM组的TG／HDL．C、TC／HDL—C及LDL．C／HDL—C比值均显著高于对照组（P〈0．01）,且均与HOMA-IR呈正相关（P〈0．01）。ROC曲线分析表明TC／HDL．C用于诊断T2DM合并胰岛素抵抗时具有较高的敏感性和特异性。结论T2DM患者血清脂蛋白比值与胰岛素抵抗之间呈正相关,对T2DM合并胰岛素抵抗的诊断及指导治疗具有重要参考价值。     

CTLA-4基因第1外显子49位点基因多态性与2型糖尿病的相关性研究

目的探讨细胞毒性T淋巴细胞相关抗原（CTLA-4）基因第1外显子49位点基因多态性与2型糖尿病（T2DM）的相关性。方法利用聚合酶链反应（PCR）-限制性酶切长度多态性（RFLP）的方法检测T2DM组111例和对照组（NC组）39例CTLA-4基因第1外显子49位点多态性。结果T2DM组与NC组CTLA-4基因第1外显子49位点基因型分布及等位基因频率比较差异无统计学意义（P〉0．05）。T2DM患者各基因型的临床资料比较：GG组的总胆固醇有下降趋势。CTLA-4基因第1外显子49位点GG基因型有起病年龄相对更早的趋势和胰岛素应用比例更高的趋势。结论CTLA-4基因第1外显子49位点基因多态性分布与T2DM发病无明显相关性，但G等位基因仍有可能是T2DM的易感因素之一。     

甘露糖结合凝集素基因与中国北方汉族人群2型糖尿病的关系

目的 探讨甘露糖结合凝集素(MBL)基因与中国北方汉族人群2型糖尿病(T2DM)的关系。方法收集318例北方汉族T2DM患者和448名血糖正常健康对照,应用多重SNaPshot技术检测MBL2基因rs 1800450、rs1800451和rs11003125位点多态性。Logistic回归分析该基因变异和其他危险因素对T2DM的作用。Haploview软件对3个位点进行连锁不平衡分析和单倍型分析。结果rs1800451位点检测到的基因型均为CC,在病例和对照中均不存在变异,rs1800450和rs11003125位点多态性的分布符合Hardy-Weinberg平衡。Rs 1800450多态位点基因型频率和等位基因频率在病例组和对照组中分布的差异均有统计学意义(P=0.006和P=0.003),rs11003125多态位点基因型频率和等位基因频率的差异也均有统计学意义(P=0.010和P=0.004)。多元logistic回归模型分析显示超重、中心性肥胖、高胆固醇血症是T2DM的危险因素。携带rs1800450位点GG基因型以及rs11003125位点(GC+CC)基因型患T2DM危险显著增高。单倍型分析结果显示rs1800450和rs11003125单倍型构成为GC患糖尿病的风险明显增高(OR=2.21,95％ CI:1.47～3.33,P=0.000)。结论 MBL2基因第1外显子rs 1800450多态、启动子rs11003125多态与T2DM可能相关。携带rs1800450位点G等位基因以及rs11003125位点C等位基因可能是汉族人群发生T2DM的危险因素。     

ACE基因多态性与T2DM患者股动脉内中膜厚度的关系

目的 探讨人类血管紧张素转换酶（ACE）基因插入/缺失多态性（I/D）与2型糖尿病（T2DM）患者股动脉内中膜厚度（FA-IMT）的关系。方法 采用限制性片段长度多形态多聚酶链式反应（PCR-RFLP）技术检测了303例T2DM患者和93例健康个体ACE基因内含子16插入/缺失（I/D）多态性，利用B型超声检测T2DM患者FA-IMT的情况。结果与健康对照组比较，T2DM患者Ⅰ等位基因频率显著增高，而D等位基因频率显著降低。携带ACEDD基因型者FA-IMT增厚的比例显著高于携带Ⅱ及ID基因型者（P〈0．01）；多元线性逐步回归分析显示，与T2DM患者基线FA-IMT关系密切的指标为年龄、ACEDD基因型、饮酒史。结论 ACEDD基因型是他DM患者FA-IMT增加的独立的危险因素。     

SLC30A8基因rs13266634多态性与甘肃回族2型糖尿病的关系

目的 研究Solute carrier family 30,member8(SLC30A8)基因多态性在甘肃回族人群中的分布并探讨其与2型糖尿病的关系.方法 应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法检测甘肃回族2型糖尿病患者(T2DM组)和正常对照者(NC组)SLC30A8基因多态性.结果 SLC30A8基因型和等位基因频率在T2DM组和NC组中的分布差异有统计学意义(P均＜ 0.05),C等位基因携带者患2型糖尿病的风险是T等位基因的1.56倍(OR=1.56,95％ CI为1.09～2.22).结论 SLC30A8基因rs13266634多态性位点的C等位基因是2型糖尿病风险等位基因,SLC30A8基因是甘肃回族人群2型糖尿病的易感基因之一.     

221名汉族人胰岛素受体底物-2基因G1057D多态性的研究

胰岛素受体底物(IRS)主要连接胰岛素受体和多种效应分子。介导细胞对胰岛素(INS)等的反应。基因剔除研究显示，IRS-1纯合突变(IRS-1^-J-)鼠仅出现胰岛素抵抗(IR)，而IRS-2^-J-鼠具有2型糖尿病(T2DM)的全部特征。本研究用PCR-RFLP方法检测辽宁地区中年汉族人群IRS-2G1057D多态性，并结合T2DM发病机制相关的INS分泌和作用的简易指标的变化．明确IRS2G1057D多态性与T2DM的相关性。     

诱发胰岛素抵抗基因与中国汉族人群2型糖尿病易感性的研究进展

2型糖尿病(T2DM)是由基因和环境共同作用所引起的慢性代谢功能紊乱疾病,主要以外周胰岛素抵抗和胰岛β细胞分泌胰岛素功能受损为特征。随着单核苷酸多态性(SNP)扫描技术的发展和人类基因组计划的完成,有10多个基因被证实与诱发胰岛素抵抗相关。此外,不同地区的中国汉族T2DM患者与胰岛素抵抗基因的相关性不同。本文就中国不同地区,汉族人T2DM易感性与胰岛素抵抗基因的相关性进行综述。     

细胞间粘附分子-1基因K469E多态性与缺血性脑卒中的相关性研究

目的探讨细胞间粘附分子-1（ICAM-1）基因K469E多态性与缺血性脑卒中发病风险的相关性。方法收集深圳市两家大型综合性医院的309名缺血性脑卒中新发病例，按年龄相差〈5岁，性别、民族相同的匹配条件选取对照，采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）检测其基因型。结果病例组ICAM-1基因K469E基因型频率和等位基因频率与对照组比较差异有统计学意义（P〈0．05）。以KK基因型为参照，病例组携带EE、EK基因型是对照组发生脑卒中危险的2．49倍和1．65倍，95％可信区间分别为1．54～4．04，1．27～2．15，而携带至少一个突变基因的个体发生脑卒中的OR值和95％可信区间为1．76（1．30～2．37）。结论ICAM-1基因K469E多态性与缺血性脑卒中发生的易感性有关，E等位基因可能是脑卒中发生的遗传易感标记，纯合突变EE基因型可能是脑卒中的危险因素。     

Neonatal diabetes mellitus: description of two Puerto Rican children with KCNJ11 activating gene mutation

Neonatal diabetes mellitus (NDM) is a rare disorder. A one-month-old boy presented with vomiting, hyperglycemia (968 mg/dl [53.8 mmol/L]), severe acetonemia, and metabolic acidosis (pH 6.95, HCO3-4.2 mmol/L). A second child (three months of age) presented with upper respiratory tract symptoms and a plasma glucose level of 835 mg/dl, without acetonemia or acidosis. Both were hospitalized and managed with intravenous fluids and then discharged on insulin. Genetic testing identified the presence of the de nova V59M and E322K activating mutations in the KCNJ11 gene encoding the sulphonylurea/potassium channel (Kir6.2 subunit) of the insulin beta cell. Both patients were switched to glibenclamide and remain off insulin. To our knowledge, these are the first children in Puerto Rico identified with NDM secondary to a KCNJ11 activating mutation. We conclude that NDM secondary to KCNJ11/Kir6.2 activating mutations, although unusual, should be considered in similar cases since patients with these mutations could come off insulin.     

中国人群细胞间黏附分子-1基因K469E多态性与冠心病相关性的Meta分析

目的研究细胞间黏附分子-1(ICAM-1)基因K469E多态性与中国人群冠心病的相关性。方法全面检索关于ICAM-1基因K469E多态性与冠心病相关性的原始研究,将符合入选标准的研究纳入,并进行数据合并。利用ICAM-1基因的KK KE基因型/EE基因型的OR值及其95/可信区间(CI)作为效应指标进行分析。采用SPSS11.5和Stata8.0统计软件包进行统计,计算合并的效应指标。结果6个原始研究共计1875例对象(其中冠心病患者897例,非冠心病者978例)进入了最后的数据合并。对各研究的两组对象进行Hardy-Weinberg遗传平衡检验,均符合遗传平衡分布。各研究间存在异质性,但未发现显著性发表偏倚。经随机效应模型(D-L法)合并的(KK KE)基因型/EE基因型的OR值为1.99,95/CI为1.19～3.31,P=0.008。结论ICAM-1基因K469E多态性可能与中国人群冠心病相关,K等位基因携带者患冠心病的危险性可能有增高趋势。     

Leptin receptor gene variation predicts weight change in subjects with impaired glucose tolerance

The leptin receptor (OB-R) gene is a promising candidate gene for type 2 diabetes, because leptin and its receptor play an important role in insulin secretion and the development of obesity. Therefore, we studied whether the pentanucleotide insertion polymorphism of the 3'-untranslated region (3'UTR) of the OB-R gene has an influence on the conversion from impaired glucose tolerance (IGT) to type 2 diabetes in the STOP-Noninsulin-Dependent Diabetes Mellitus trial. The STOP trial was a longitudinal, double-blind, placebo-controlled randomized trial that included 1429 subjects with IGT from high-risk populations. Using the restriction fragment length polymorphism method, we genotyped 770 subjects whose DNA was available for the insertion/deletion polymorphism of the 3'UTR of the OB-R gene. We did not find a relationship between the OB-R polymorphism and the conversion from IGT to type 2 diabetes (p = 0.747). However, the insertion allele was associated with a significant reduction in weight (p = 0.016), BMI (p = 0.009), and waist circumference (p = 0.006) in all subjects. Women carrying the I allele had a larger waist circumference change (p = 0.036), whereas men lost more weight and had a greater decrease in BMI. The pentanucleotide insertion/deletion polymorphism in the 3'UTR of the OB-R gene did not influence the conversion to type 2 diabetes in obese patients with IGT. However, this polymorphism was associated with a significant weight change, suggesting that it may potentially modulate the risk for type 2 diabetes.     

细胞间粘附分子-1基因多态性与动脉硬化性脑梗死的相关性研究

目的：研究细胞间粘附分子-1（ICAM-1）469K〉E多态性位点等位基因分布频率及其与ACI的关系。方法：选择121名湖北地区健康汉族人及92名ACI患者,应用等位基因特异性PCR（巢式PCR）,对每个个体的基因型进行鉴定。同时,采用酶法、免疫比浊法及酶联免疫吸附试验（ELISA）对研究对象血脂和ICAM-1水平进行检测。结果：二组间除性别、年龄及BMI无明显差异外,其它各项指标（吸烟、TC、TG、HDL-C、LDL-C、ICAM-1）均有明显差异（P〈0.01）;469K〉E位点,ACI组稀有等位基因E的频率明显高于对照组（χ^2=11.93,P=0.001）,KK、KE、EE 3种基因型在二组中的分布频率有明显差异（χ^2=34.94,P=0.000）,且二组中KK、KE、EE 3种基因型TG与ICAM-1水平差异有统计学意义（P〈0.01）。结论：ICAM-1 469E等位基因与ACI患者TG及ICAM-1水平升高有关,可能是该地区人群ACI的危险因子。     

Association of polymorphisms in nicotinic acetylcholine receptor alpha 4 subunit gene (CHRNA4), mu-opioid receptor gene (OPRM1), and ethanol-metabolizing enzyme genes with alcoholism in Korean patients.

Findings obtained from several studies indicate that ethanol enhances the activity of alpha4beta2 neuronal nicotinic acetylcholine receptor and support the possibility that a polymorphism of the nicotinic acetylcholine receptor alpha4 subunit gene (CHRNA4) modulates enhancement of nicotinic receptor function by ethanol. To identify the association between the CfoI polymorphism of the CHRNA4 and alcoholism, we examined distribution of genotypes and allele frequencies in Korean patients diagnosed with alcoholism (n = 127) and Korean control subjects without alcoholism (n = 185) with polymerase chain reaction-restriction fragment length polymorphism methods. We were able to detect the association between the CfoI polymorphism of the CHRNA4 and alcoholism in Korean patients (genotype P = .023; allele frequency P = .047). The genotypes and allele frequencies of known polymorphisms in other alcoholism candidate genes, such as alcohol metabolism-related genes [alcohol dehydrogenase 2 (ADH2), aldehyde dehydrogenase 2 (ALDH2), alcohol dehydrogenase 3 (ADH3), and cytochrome P450 2E1 (CYP2E1)] and mu-opioid receptor gene (OPRM1), were studied. The polymorphisms of ADH2, ALDH2, and CYP2E1 were significantly different in Korean patients with alcoholism and Korean control subjects without alcoholism, but ADH3 and OPRM1 did not differ between the two groups.     

The -11377C > G adiponectin gene polymorphism alters the adiponectin concentration and the susceptibility to type 2 diabetes in Thais

The aims of this study were first to detect the levels of adiponectin, insulin, albumin, glucose, alanine aminotransferase (ALT), lipids, homeostasis model assessment for insulin resistance (HOMA-IR), and anthropometric variables in type 2 diabetes mellitus (T2DM) as well as healthy control groups, and to determine whether two adiponectin gene polymorphisms, at the position -11377C > G as well as +45T > G, are associated with serum levels of adiponectin and other variables; then to search for the association between these two single nucleotide polymorphisms (SNPs) of the adiponectin gene and T2DM. We investigated 93 T2DM patients and 90 healthy volunteers. Compared with the healthy control group, the T2DM group had significantly lower adiponectin levels. Waist circumference, total cholesterol, ALT, glucose, insulin, and HOMA-IR scores were significantly higher in the T2DM group than in the control group. The polymorphism of the adiponectin gene at position -11377C > G among type 2 diabetes subjects showed that the adiponectin concentration was significantly lower in CG/GG genotypes (6.2 μg/mL) than the CC genotype (7.8 μg/mL), whereas SNP +45T > G was not associated with adiponectin levels. Adiponectin gene polymorphisms at position -11377C > G and +45T > G were significantly more frequent in type 2 diabetes patients than in the control group (p = 0.022; p = 0.045, respectively). However, multivariate logistic regression analysis showed that the strong impact on T2DM was found for -11377C > G gene polymorphism (p = 0.023) and waist circumference (p < 0.001). Therefore, the single nucleotide polymorphism of -11377C > G in adiponectin promoter region has impact on the lower adiponectin concentrations, and may influence susceptibility to T2DM in Thais.     

Calpain10基因多态性与昆明地区人群2型糖尿病相关性研究

目的 探讨Calpain10基因多态性与昆明地区人群2型糖尿病遗传易感性的关系。方法采用病例-对照研究设计，以聚合酶链式反应-等位基因特异性扩增法（PCR-ASA），检测Calpain10基因单核苷酸多态性（SNP）43G／A位点和SNP44T／C位点基因型，并进行关联分析。结果 对131例2型糖尿病患者和131例正常对照进行了Calpain10基因SNP43和SNP44基因分型，与对照组相比，SNP43的G等位基因频率和SNP44的C等位基因频率在昆明地区2型糖尿病人群中显著升高（分别为93．13％，86．26％，P=0．0097；18．70％，9．92％，P=0．004）。结论 Calpain10基因SNP43位点G等位基因和SNP44位点C等位基因可能与昆明地区人群2型糖尿病的发病相关。     

肌糖原合酶基因多态性与天津地区中老年人2型糖尿病及其合并高血压关系的研究

目的研究天津地区中老年人群中肌糖原合酶基因(GYS1)内含子14第377bp多态性与2型糖尿病(2型DM)及其合并高血压的关系。方法采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法对275例中老年2型DM患者(包括159例合并高血压者)和115例中老年正常对照者的内含子14第377bp进行多态性筛查,并经测序证实。结果在275例2型DM患者(包括159例合并高血压者)中未检出A2等位基因。在115例正常对照者中发现1例A1/A2基因型,没有发现A2/A2基因型,A2等位基因频率为0.0043,A1/A2基因型频率为0.0087,其频率明显低于国内外大多数报道。在2型DM患者和正常对照组之间A2等位基因的频率差别无统计学意义。2型DM合并高血压组与2型DM正常血压组之间A2等位基因频率无差别。结论天津地区中老年人群中GYS1内含子14第377bp多态性可能与2型DM及其合并高血压无关。该多态性可能只是部分种族、部分人群2型DM及高血压的遗传标记。