2型糖尿病患者胰升糖素受体基因的PCR—EGGE调查

目的 探讨胰升糖素受体（ＧＣＧ－Ｒ）基因在中国人２型糖尿病遗传背景中的地位。方法运用聚合酶链反应变性梯度凝胶电泳（ＰＣＲ－ＤＧＧＥ）技术对２００例无亲缘关系之中国云南昆明地区汉族人（２型糖尿病患者１２０例,健康对照者８０例）的ＧＣＧ－Ｒ基因编码区进行了分子扫查。结果 仅发现２例２型糖尿病患者及１例健康对照者的ＧＣＧ－Ｒ基因第７外显子存在多态变异带型,这一杂合子多态变异基因型在２型糖尿病组和对照组中     

2型糖尿病患者内皮源型一氧化氮合酶基因第4内含子多态性与高甘油三酯水平的关系

目的 探讨内皮源型一氧化氮合酶(ecNOS)基因第4内含子的27重复核苷酸序列多态标记在中国昆明地区汉族人群中的分布及其与2型糖尿病的相关性。方法 选择212例无亲缘关系的中国云南昆明地区汉族人，其中2型糖尿病的患者132例，无糖尿病家族史的健康对照者80例。应用聚合酶链反应(PCR)技术检测ecNOS基因第4内含子的27重复核苷酸序列多态标记。结果 在中国昆明地区汉族人群中含有4a(4重复系列)等位基因的频率为0．083。在2型糖尿病患者及正常对照者中含有4a等位基因的频率分别为0．087及0．075(P＞0．05)。与ecNOS4b纯合子(5重复系列)的人群相比，带有ecNOS4a等位基因的人群的血清甘油三酯水平显著增高[2．260(1．805—3．640)vsl.656(1.605—2．163)mmol／L，P＝0．02]。结论 ecNOS基因与血清高甘油三酯水平相关。     

山东省汉族人β_3肾上腺能受体基因多态性分析

应用多聚酶链反应 -限制性片段长度多态性 (PCR- RFL P)技术对 2 12例山东省汉族人 (非糖尿病 80例 ,2型糖尿病 132例 )进行 β3 肾上腺能受体 (β3 AR)基因 Trp6 4 Arg突变分析。结果表明 ,山东汉人β3 AR Trp6 4 Arg等位基因变异频率为 15% ,2型糖尿病组与非糖尿病组β3 AR Trp6 4 Arg基因型和等位基因分布频率无显著差异 (P>0 .0 5)。提示山东省汉族人存在 β3 AR基因变异 ,但这种变异与2型糖尿病无密切关联     

ACE基因、AT1R基因多态性与2型糖尿病肾病的关系

目的研究血管紧张素I转化酶(ACE)基因/D多态及血管紧张素受体1型(AT1R)A1166C多态性与中国汉族人2型糖尿病肾病(DN)的关系。方法运用聚合酶链反应(PCR)和PCR/DdeI酶切技术,检测93例DN患者(DN组)与94例2型糖尿病患者(DM组)ACE基因及AT1R基因多态基因型。结果DN组ACE基因DD基因型频率(34.4%)、D型等位基因频率(54.3%)较DM组(19.1%,40.4%)均升高(P<0.05,<0.01);两组间AT1R基因A1166C多态基因型频率和等位基因频率分布均无差异(P>0.05);ACE和AT1R基因多态与DN的分层分析显示,同时携带ACE纯合子缺失基因型(DD)和AT1R突变基因型(AC+CC)者发生DN的危险较大,OR值为8.569。结论ACE基因/D多态性与2型DM并发DN有关,携带DD基因型和D型等位基因的2型DM患者是DN的易感人群。ATlR基因A1166C多态性虽与我国汉族人2型DM并发DN无关,但AT1R与ACE基因多态存在协同效应,携带AC+CC与DD基因型的个体有更高的患DN风险。     

中国人2型糖尿病微血管并发症与AGE受体基因Gly82Ser多态性相关研究

目的　探讨 AGE受体 (RAGE)基因 Gly82 Ser多态性与中国人 2型糖尿病微血管并发症间的关系。方法　使用限制性内切酶 Alu I(AG↑ CT)的 PCR- RFL P法 ,检测 10 4例非糖尿病对照者和 15 6例 2型糖尿病伴或不伴肾病、视网膜病变者的 RAGE基因 Gly82 Ser的多态基因型。结果　中国人 RAGE基因 Gly82 Ser多态基因型以 GG型、等位基因以 G型为最多见 ,但频率分布与白种人相比有显著性差异。非 DM对照组与 2型糖尿病伴或不伴有肾病的 4个亚组间、与伴或不伴有视网膜病变的 2个亚组间 ,RAGE基因的 Gly82 Ser多态的基因型 (GG、GS、SS)频率或等位基因 (G、S)频率皆无显著性差异 (Fisher's确切 P值 >0 .0 5 )。结论　 RAGE基因的 Gly82 Ser多态引起的 RAGE功能性氨基酸突变与 2型糖尿病微血管并发症的发生及进展无显著性相关     

蛋白酪氨酸磷脂酶-1B基因Pro387Leu变异与2型糖尿病的相关性研究

目的　探讨广州地区汉族人中蛋白酪氨酸磷脂酶 1B(PTP 1B)基因Pro387Leu变异与2型糖尿病 (T2DM)的相关性。　方法　随机选取无亲缘关系的广州地区汉族人 5 6 7例 ,其中T2DM患者 32 9例 ,正常对照 2 38例 ,应用聚合酶链反应 限制性片段长度多态性 (PCR RFLP)进行Pro387Leu变异的检测。　结果　正常对照组PTP 1BLeu 387携带者及Leu 387等位基因频率分别是 0 8%、0 4 % ,T2DM组相应为 0 6 %、0 3% ,两组比较差异无统计学意义 (P >0 0 5 )。　结论　PTP 1B基因Pro387Leu变异与汉族人T2DM的发生不相关。     

对氧磷酯酶192Gln/Arg基因多态性与2型糖尿病合并冠心病的相关性研究

目的　探讨对氧磷酯酶 192Gln/Arg基因多态性与 2型糖尿病合并冠心病的关系。　方法　采用多聚酶链反应 限制性片段长度多态性 (PCR RFLP)法检测 10 4例健康对照者 (作为正常对照组 )和 80例 2型糖尿病、96例 2型糖尿病合并冠心病 (CDH)患者PON1 192位点的多态基因型。测量体重指数、总胆固醇、甘油三酯、高密度脂蛋白、低密度脂蛋白、载脂蛋白AI及载脂蛋白B。　结果　 ( 1)中国汉族人PON1 192位点QQ、QR、RR基因型频率及Q、R等位基因频率 :2型糖尿病合并CHD组与正常对照组比较差别有显著性 ;与单纯糖尿病组比较差别无显著性。 ( 2 )中国人与白种人PON1 192位点基因型频率及等位基因频率比较差别非常显著。 ( 3)含R等位基因的基因型QR、RR是 2型糖尿病合并CHD的独立危险因素。　结论　对氧磷酯酶 192Gln/Arg基因多态性与 2型糖尿病合并CHD相关。     

对氧磷酯酶l92Gln／Arg基因多态性与2型糖尿病合并冠心病的相关性研究

目的 探讨对氧磷酯酶192G1n／Arg基因多态性与2型糖尿病合并冠心病的关系。方法 采用多聚酶链反应—限制性片段长度多态性(PCR—RFLP)法检测104例健康对照者(作为正常对照组)和80例2型糖尿病、96例2型糖尿病合并冠心病(CDH)患者PONl—192位点的多态基因型。测量体重指数、总胆固醇、甘油三酯、高密度脂蛋白、低密度脂蛋白、载脂蛋白AI及载脂蛋白B。结果 (1)中国汉族人PONl—192位点QQ、QR、RR基因型频率及Q、R等位基因频率：2型糖尿病合并CHD组与正常对照组比较差别有显著性；与单纯糖尿病组比较差别无显著性。(2)中国人与白种人PONl—192位点基因型频率及等位基因频率比较差别非常显著。(3)含R等位基因的基因型QR、RR是2型糖尿病合并CHD的独立危险因素。结论 对氧磷酯酶192G1n／Arg基因多态性与2型糖尿病合并CHD相关。     

ApoE基因多态性与中国人2型糖尿病及其肾病并发症的关系

目的　研究 Apo E基因多态性与中国人 2型糖尿病及其肾病并发症的关系。方法　以载脂蛋白 E(Apo E)基因为候选基因 ,运用聚合酶链反应——限制性片段长度多态性 (PCR- RFL P)方法检测了 2 6 5例 2型糖尿病患者 ,其中未合并肾病者 10 6例 ,合并肾病者 15 9例 ,后者又分为蛋白尿者 12 2例 ,肾功能不全者 37例及 110例非糖尿病对照者的Apo E基因型。结果　 12型糖尿病合并肾病组与 2型糖尿病未合并肾病组相比 ,等位基因 ε2频率显著升高 (P=0 .0 0 894 ) ;基因型 E2 (E2 / 2 E2 / 3)组频率也显著升高 (P=0 .0 0 194 )。 2 2型糖尿病组与非糖尿病对照组相比基因型频率及等位基因频率均无显著性差异 (均 P>0 .0 5 )。结论　Apo E等位基因 ε2可能是 2型糖尿病合并肾病的危险因子。Apo E基因多态性与中国人 2型糖尿病发病无相关性     

常见型非胰岛素依赖型糖尿病患者的葡萄糖激酶基因分子扫查

对３０例起病于４５岁或以前及／或伴糖尿病家族史的中国人常见型非胰岛素依赖型糖尿病（ＮＩＤＤＭ）患者，进行葡萄糖激酶基因（ＧＣＫ）编码区及拼接区分子扫查。就扫查中发现的突变／变异，进一步在５６例ＮＩＤＤＭ者及１３４例非糖尿病患者中筛查，确认其频率。结果表明：①分子扫查未见ＧＣＫ编码区及拼接区突变，提示此类突变不是中国人常见型ＮＩＤＤＭ主要病因。②中国人常见型ＮＩＤＤＭ中，尤其是起病早及伴有明显糖尿病家族史者，可伴ＧＣＫ内含子１ｂ变异，此种变异未见于非糖尿病患者（４．７％比０％，Ｆｉｓｈｅｒ确切Ｐ值＝０．０２２）。此变异是否影响ＧＣＫ表达尚待阐明。     

胰升糖素受体基因变异与2型糖尿病的关系

目的探讨中国人２型糖尿病与胰升糖素受体（ＧＣＧＲ）基因４０号密码子的错义突变（Ｇｌｙ４０Ｓｅｒ）是否存在关联。方法运用聚合酶链反应—限制性片段长度多态性（ＰＣＲＲＦＬＰ）分析方法在２００例无亲缘关系之中国云南昆明地区汉族人（２型糖尿病患者１２０例,健康对照者８０例）中对ＧＣＧＲ基因Ｇｌｙ４０Ｓｅｒ突变进行检测。结果本文所有研究对象中无论是２型糖尿病患者还是健康对照者均无一例存在ＧＣＧＲ基因Ｇｌｙ４０Ｓｅｒ突变,其ＧＣＧＲ基因４０号密码子的基因型均表现为Ｇｌｙ４０／Ｇｌｙ４０之纯合子,Ｇｌｙ４０和Ｓｅｒ４０等位基因频率均分别为１和０。２型糖尿病患者与健康对照者无任何差异。结论在中国云南昆明地区的汉族人中,ＧＣＧＲ基因Ｇｌｙ４０Ｓｅｒ突变与２型糖尿病不存在任何关联     

Analysis of the insulin-sensitive phosphodiesterase 3B gene in type 2 diabetes

We screened for mutations in the gene of insulin-sensitive phosphodiesterase 3B (PDE3B), which regulates antilipolytic actions of insulin via reduction of intracellular cyclic AMP levels, in Japanese patients with type 2 diabetes mellitus and lipoatrophic diabetes mellitus using single-stranded conformation polymorphism analysis and Southern analysis and investigated frequencies of variable number of tandem repeats. A silent polymorphism at the Arg463 codon (AGG-->AGA) in exon 4 was identified after examining all 16 exons and exon-intron splicing junctions of the gene. This polymorphism was found in 53 of 100 subjects with type 2 diabetes mellitus, 2 of 5 lipoatrophic diabetic patients and 24 of 50 control subjects, without any significant difference in allele frequency between groups. An EcoRI restriction fragment length polymorphism was identified in patients with type 2 diabetes mellitus and control subjects, again with no differences in occurrence. The allelic distribution of two polymorphic tandem repeats sequences in introns 5 and 12 of the gene did not differ significantly between patients with type 2 diabetes mellitus and control subjects. In conclusion, alterations in the PDE3B gene are unlikely to contribute importantly to the pathogenesis of type 2 diabetes mellitus or lipoatrophic diabetes mellitus in Japan.     

醛糖还原酶基因多态性与糖尿病微血管并发症的相关性研究

目的　探讨醛糖还原酶（ＡＲ）基因多态标记（ＡＣ）ｎ 与中国人２ 型糖尿病微血管并发症之间的关系。方法　用３２Ｐ引物末端标记法,经聚合酶链反应变性聚丙烯酰胺凝胶电泳,检测３６２ 例中国人（２１７ 人为２ 型糖尿病,其中１５６ 人合并肾病或视网膜病变,１４５ 人为非糖尿病对照）ＡＲ 基因的二核苷酸（ＡＣ）ｎ 串联重复序列多态标记,比较各组间的等位基因频率和基因型频率。结果　（１）在非糖尿病对照者和２ 型糖尿病患者中,见到七种ＡＲ 基因的等位基因,其中以（ＡＣ）２４（１３８ｂｐ） 等位基因（Ｚ）最常见。（２）同时合并肾病和视网膜病变的２ 型糖尿病组与无并发症的２ 型糖尿病组相比,Ｚ＋ ６等位基因频率显著减少（Ｆｉｓｈｅｒ 确切, Ｐ＝０ ．０３８）, 含Ｚ＋ ６ 等位基因的基因型频率也显著减少（Ｐ＝０．００４）。（３） 无并发症的２ 型糖尿病组与对照组比较其Ｚ＋ ６ 等位基因频率显著增加（ Ｐ＝ ０．０４４） 。（４）２ 型糖尿病合并肾病伴肾功能不全者与不伴有肾病的２ 型糖尿病者相比,Ｚ－ ２ 等位基因频率显著增加（ Ｐ＝ ０ ．０３９）,同时含Ｚ－ ２ 等位基因的基因型频率也呈增加趋势。结论　ＡＲ 的Ｚ－ ２ 等位基因是促进中国人２ 型糖尿病并发严     

Coronary artery disease risk in Chinese type 2 diabetics: is there a role for paraxonase 1 gene (Q192R) polymorphism?

OBJECTIVE: Heredity plays an important role in the predisposition to atherosclerotic coronary artery disease (CAD), and its thrombotic complications. Paraoxonase, a high-density lipoprotein-associated enzyme capable of hydrolyzing lipid peroxides, is presumed to contribute to atherosclerosis and CAD. This study investigates the role of human paraoxonase 1 (PON 1) gene (Q192R) polymorphism in CAD risk among Chinese type 2 diabetic cases. DESIGN: A population-based case-control study of paraoxonase 1 gene (Q192R) polymorphism and the risk of CAD in Chinese type 2 diabetics. METHODS: Subjects included 201 angiographically documented CAD patients with type 2 diabetes and 231 control subjects with type 2 diabetes alone living in central China. Single strand conformational polymorphism (SSCP) analysis was used to screen for PON 1 gene (Q192R) polymorphism. RESULTS: Frequency of the R allele was 21.5% in the CAD patients and 12.0% in the control subjects. The presence of the R allele was significantly associated with risk of CAD (odds ratio (OR)=1.97; 95% confidence interval (CI)=1.36--2.86). CONCLUSION: Frequency of the 192R allele of the human paraoxonase 1 gene may be an independent risk factor for CAD in the Chinese type 2 diabetics studied.     

硫酸乙酰肝素蛋白多糖基因多态性与糖尿病肾病关系的研究

目的：探讨硫酸乙酰肝素蛋白多糖基因（HSPG）多态性与中国汉族人2型糖尿病肾脏并发症之间的关系,方法：应用限制性内切酶BamHI的PCR－RFLP法,检测190例非DM对照和136例2型糖尿病伴或不伴肾病者的HSPG多态性基因型。结果：正常白蛋白尿组和异常（微量和大量）白蛋白尿组之间BamHI HSPG2等位基因频率和基因型频率无显著性差异。非MD对照组和糖尿病组之间BamHI HSPG2等位基因频率无显著性差异,但基因型频率的差异有统计学意义。结论：中国汉族人B HI贡HSPG2多态性与2型糖尿病肾脏并发症的发生无显著性相关关系,但其基因型频率似与糖尿病发病有关。     

Autoimmune thyropathies in diabetics

Autoimmune thyropathies are frequent in patients with type 1 diabetes mellitus. Some recently published papers confirm similarly high prevalence of autoimmune thyropathies also in patients with type 2 diabetes mellitus. Chronic autoimmune thyroiditis is the most frequent form of autoimmune thyropathies. Authors examined 79 accidentally selected diabetics (38 women and 41 men, x = 55.4 +/- 2.8). Diabetic patients were divided into three groups. 20 patients with type 1 diabetes mellitus - classical form were the first group, 12 patients with LADA were the second group and 47 patients with type 2 diabetes mellitus constituted the third group. Authors diagnosed chronic autoimmune thyroiditis in 8 (40 %) patients in the group of patients with type 1 diabetes mellitus, in 6 (50%) in the group of patients with LADA and in 20 (43%) of patients with type 2 diabetes mellitus. They didn't find out statistically more frequent prevalence of chronic autoimmune thyroiditis in all groups of patients with diabetes (patients with type 1 diabetes mellitus, patients with LADA, patients with type 2 diabetes mellitus) in comparison with control group of non-diabetic subjects. They found out statistically significant more frequent prevalence of chronic autoimmune thyroiditis in diabetics of woman gender and in diabetics with positive family history of thyropathies. Results of paper confirm recommendation of examining once or twice a year autoantibodies against thyroid gland and level of thyrotropin (TSH) with the aim of early finding of laboratory manifestation of thyroidal autoimmunity or developing functional disorder.     

蛋白酪氨酸磷酸酶1B基因1484插入G变异与中国人肥胖相关

目的 确定蛋白酪氨酸磷酸酶1B（PTPIB）基因1484插入G（insG）变异是否与中国人肥胖相关。方法 选取上海地区中国人305例，用PCR／SacⅡ酶解法检测1484insG突变，突变的样本全部进行DNA序列分析。结果 正常对照组、单纯性肥胖、肥胖合并2型糖尿病组各发现8例、10例、16例PTP1B1484insG突变，正常对照组的1484insG突变率与单纯肥胖组、肥胖总组比较差异无统计学意义。但正常对照组与肥胖合并2型糖尿病组比较差异有统计学意义（P〈0．05），单纯肥胖组与肥胖合并2型糖尿病组比较差异无统计学意义（P〉0．05）。结论 PTP1B基因1484insG突变与中国人肥胖伴2型糖尿病有相关性，可能是中国肥胖人群发生2型糖尿病的遗传因素之一。     

The relationship of lmp2 and DR3 genes with susceptibility to type I diabetes mellitus in south China Han population

AIM:To study the relationship of lmp2 and DR3 genes with type I diabetes mellitus.METHODS:lmp2 genotypes and DR3 were identified in 68 patients with type I diabetes mellitus (I -DM) and 71 healthy controls. Then,I -DM patients and controls were respectively allocated into DR3-positive and DR3-negative groups. The frequencies of lmp2 and DR3 gene in random subjects, and lmp2 genotypes in DR3 matched subjects were compared between I -DM patients and controls. At the same time, I DM patients were divided into 3 groups based on the onset age of diabetics:group A < = 14 years, group B 15-30 years and group C > = 31 years.RESULTS:The frequency of DR3 in I-DM patients was significantly higher than that in controls (47% vs 21%, P < 0.005), and it was significantly higher in group A than that in group B+C (70% vs 36%, X(2) = 7.07, P < 0.01). There was a significant difference among groups with different onset age of diabetics (X(2) = 8.19, rp = 0.33, P <0.05). In random subjects, the frequency of lmp2-R/R in I -DM patients was lower (43% vs 61%, P <0.05)and lmp2-R/H higher (53% vs 28%, P<0.05) than that in controls, and there was no significant difference among groups with different onset age of diabetics.In DR3-positive subjects, the frequency of lmp2-R/R in I-DM patients was lower (47% vs 87%, P<0.05) and lmp2-R/H higher (47% vs 13%, P <0.05) than that in controls. In DR3-negative subjects,the frequency of lmp2-R/H in I -DM patients was higher than that in controls (58% vs 32%, P <0.01), but the frequency of lmp2-R/R and lmp2-H/H was not significantly different between these two groups.CONCLUSION:DR3 gene may be one of the susceptible genes of I-DM,and significantly related to the onset age of diabetics, and the persons with DR3 may have an younger onset age of diabetes.The lmp2-R/R may be the protective genotype of I-DM, and lmp2-R/H the susceptible genotype. These were not affected by DR3 gene. lmp2 genotypes were not related with the onset age of diabetics.     

D2S140基因多态性与2型糖尿病的相关性研究

目的：探讨D2S140基因多态性与2型糖尿病的关系。方法：运用聚合酶链反应（PCR）技术,结合短串联重复序列（STR）多态性标记的方法,检测了103例2型糖尿病患者和105例正常对照者的D2S140等位基因及基因型,结果：发现7种等 位基因。等位基因2与2型糖尿病呈显著性正相关（RR＝13。76,P＜0．001）,等位基因6与2型糖尿病呈显著性负相关（RR＝0．25,P＜0．001）。多因素非条件Logistic回归分析表明,D2S140等位基因2是2型糖尿病的独立危险因素,其相对危险度明显高于环境因素。结论：DS2S140基因多态性与中国人2型糖尿病相关。