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1.
目的研究血清脂联素(APN)水平及脂联素基因单核苷酸多态性(SNP)45T→G与2型糖尿病(T2DM)视网膜病变(DR)之问的关系。方法运用聚合酶链反应-限制性片段长度多态性方法,对76例T2DM患者[无DR(NDR)组27例、非增殖型DR(NPDR)组28例、增殖型DR(PDR)组21例],和35例正常对照(Nc)者的APN基因SNP45多态性位点进行基因分型;用放射免疫法检测空腹血清APN浓度;比较各组基因型和等位基因频率,并分析各指标间的相关性。结果(1)T2DM组血清APN水平明显低于NC组(P<0.01);PDR组APN浓度明显低于NDR和NPDR组,差异有统计学意义(P均<0.01);(2)血清APN浓度与年龄、收缩压、空腹血糖、空腹胰岛素、HbA1C、TG、LDL-C、HO—MA—IR呈显著负相关;(3)SNP45多态性位点的基因型和等位基因频率在NDR、NPDR、PDR组和NC组三间无统计学差异(P〉O.05),三种基因型的血清APN水平无统计学差异(P>0.05)。结论T2DM患者血清APN水平降低,APN在DR的发病机制中发挥作用且与DR的严重度相关;而APN基因SNP45多态性位点与青岛地区汉族人群中DR无明显相关性。 相似文献
2.
血浆纤溶酶原激活物抑制因子基因启动子多态性与2型糖尿病伴发冠心病的关系 总被引:2,自引:0,他引:2
目的从分子遗传水平进行基因多态性研究,以探讨2型糖尿病易伴发冠心病的内在原因。方法对81例2型糖尿病患者、93例非糖尿病(非DM)患者进行口服糖耐量试验、血脂分析、血浆纤溶酶原激活物抑制因子(PAI1)基因多态性分析。结果2型糖尿病和非DM相比PAI1基因启动子4G频率明显增加(42%和31%,P<0001);2型糖尿病伴冠心病与不伴冠心病相比,PAI1基因启动子4G频率及4G/4G基因型频率存在明显差异(52%和30%,32%和14%;P分别<0001、005);非2型糖尿病伴冠心病与不伴冠心病相比,PAI1基因启动子4G频率及4G/4G基因型频率则无明显差异(31%和31%,8%和16%,均为P>005)。结论PAI1基因4G等位基因可能是糖尿病合并冠心病的内在危险因素 相似文献
3.
为探讨 PAI- 1基因启动子区 4 G/ 5 G基因多态性、一氧化氮合酶 (e NOS)第 4内含子 2 7bp插入 /缺失 (a/b)多态性与糖尿病肾病 (DN)的相关性 ,采用发色底物法测定 PAI- 1活性 ;等位基因特异性引物 PCR扩增技术测定 PAI- 1基因 4 G/ 5 G多态性 ;聚合酶链反应测定 e NOS基因第 4内含子 2 7bp的 a/ b多态性。结果显示 ,Hb A1c、SBP、TC、e NOS基因第 4内含子 a/ b多态均属 DN的独立危险因素。早期糖尿病肾病组 (DN+组 ) a等位基因及 ab基因型频率显著高于糖尿病非肾病组 (DN-组 ) (P<0 .0 5 )。DN+组血浆 PAI- 1活性明显高于 DN-组 (P<0 .0 5 ) ;4 G纯合子组 PAI- 1活性明显高于 4 G/ 5 G杂合子及 5 G纯合子组 (P<0 .0 0 5 )。2型糖尿病患者中 ,4 G纯合子和a/ b杂合子携带者 DN的相对风险明显增加 (P<0 .0 5 ) ,4 G杂合子携带者 DN的相对风险增加不明显 (P>0 .0 5 )。当 a/ b杂合子和 4 G纯合子基因多态并存时 DN的发病风险明显增加。认为 PAI- 1基因启动子区 4 G/ 5 G基因多态、e NOS基因第 4内含子 a/ b多态与 DN的发生、发展有关。两种基因多态同时存在时 ,DN的发病风险明显增加 相似文献
4.
目的探讨叉头框c2(FOXC2)基因5qE翻译区c-512T和G-350T多态性与2型糖尿病(T2DM)的相关性。方法选择云南省汉族人群280例,其中T2DM患者159例为T2DM组,无糖尿病家族史的健康对照121名为对照(Nc)组。应用PCR—RFLP检测FOXC2基因5q#翻译区c-512T和G-350T多态性。结果T2DM组和NC组组间,FOXC2基因C-512T和G-350T的基因型和等位基因频率分布差异均无统计学意义,且与性别无关。T2DM组-12C/C基因型携带者具有更高的wHR(P%O.05),该人群患脂肪肝的比例明显升高(P〈0.05)。-350G/G基因型携带者具有更高的HDL—C(P〈0.05),该人群患脂肪肝的比例明显降低(P〈0.01)。结论T2DM患者FOXC2基因C-512T多态性与wHR、脂肪肝相关;G-350T多态性与HDLC、脂肪肝相关。 相似文献
5.
Tyrosine phosphatase 1B and leptin receptor genes and their interaction in type 2 diabetes 总被引:3,自引:0,他引:3
OBJECTIVES: The association between three tyrosine phosphatase 1B (PTP1B) gene polymorphisms and type 2 diabetes was examined by comparing the prevalence rates of these polymorphisms in type 2 diabetic patients and healthy control subjects. Furthermore, the association of the polymorphisms and PTP1B and leptin receptor (LepR) gene-gene interactions with complications of type 2 diabetes were examined in type 2 diabetic patients. SUBJECTS AND METHODS: A total of 257 Finnish patients with type 2 diabetes and 285 nondiabetic subjects were screened. Single nucleotide polymorphisms were determined using polymerase chain reaction and restriction enzymes. The diagnosis of coronary heart disease was based on clinical and ECG criteria. The prevalences of cerebrovascular and peripheral vascular diseases were assessed on the basis of clinical criteria. Laboratory analyses were carried out in the hospital laboratory. RESULTS: We did not find any differences in the genotype distributions or allele frequencies of IVS6 + G82A and Pro387Leu polymorphisms between the type 2 diabetics and controls. There were differences in the genotype frequencies of the Pro303Pro (C981T)-polymorphism between the two studied groups (P = 0,018); there were eight T981T subjects in the control population but none amongst the type 2 diabetics. However, there were no differences in the allele frequencies. In addition, significant associations between the IVS6 + G82A polymorphism and body mass index (BMI), albuminuria, glycohaemoglobin A1 (GHBA1) and hypertension in type 2 diabetic patients (P = 0,026-0,031) were observed. Pro387Leu and Pro303Pro did not associate with risk factors or diabetic complications. We also found a gene-gene interaction effect between PTP1B and the LepR gene with the genotype combination IVS6 + A82A and Arg223Arg having the highest BMI compared with the other genotype combinations (P = 0.0043 for trend). The interaction between these two polymorphisms explained 3% of the variation in BMI in diabetic patients when the other covariates were taken into account. CONCLUSIONS: We conclude that the PTP1B IVS6 + G82A polymorphism was associated with BMI, albuminuria, GHBA1 and hypertension in type 2 diabetic patients. The 981T/T-genotype of the Pro303Pro- polymorphism might have some protective role against the development of type 2 diabetes. The interaction effects between the PTP1B IVS6 + A82A and LepR Arg223Arg genotypes influenced BMI, explaining 3% of its variation. A synergistic effect of PTP1B and LepR variants on the leptin signalling may be involved. 相似文献
6.
Adiponectin gene polymorphism (G276T) is not associated with incipient diabetic nephropathy in Japanese type 2 diabetic patients 总被引:4,自引:0,他引:4
Yoshioka K Yoshida T Umekawa T Kogure A Takakura Y Toda H Yoshikawa T 《Metabolism: clinical and experimental》2004,53(9):1223-1226
A single-nucleotide polymorphism (SNP) G276T in the adiponectin gene has been associated with lower plasma adiponectin levels and insulin resistance, which are related to the prevalence of type 2 diabetes or diabetic complications of macroangiopathy. We performed a case-control study to examine whether the SNP276 of the adiponectin gene was also related to early diabetic nephropathy. SNP276 was examined with genomic DNA obtained from 108 type 2 diabetic patients with microalbuminuria (urinary albumin creatinine ratio [ACR] between 30 mg/g x Cr and 300 mg/g x Cr; case subjects), and 208 patients with normoalbuminuria (ACR < 30 mg/g x Cr; control subjects). The genotype distribution and G allele frequency of SNP276 in the case subjects (0.71) did not significantly differ from the control subjects (0.69). There were no differences among the genotypes of the adiponectin gene regarding age, duration of diabetes, body mass index (BMI), hemoglobin A(1c) (HbA(1c)), serum lipids, serum creatinine, and plasma adiponectin levels. These data suggest that SNP276 of the adiponectin gene is not an independent risk factor for incipient diabetic nephropathy in Japanese type 2 diabetic patients. 相似文献
7.
PAI—1基因4G/5G多态性与2型糖尿病合并肾病的相关性研究 总被引:5,自引:0,他引:5
目的探讨血浆纤溶酶原激活物抑制物-1(PAI-1)基因启动子区4G/5G多态性与中国北方汉族人2型糖尿病合并肾病的相关性.方法运用等位基因特异性引物PCR扩增技术,检测病程超过10年的2型糖尿病患者(1 43例)和健康人(85例)的PAI-1基因4G/5G多态位点的基因型,用发色底物法测血浆PAI-1活性.结果 (1)糖尿病肾病组血浆PAI-1活性明显高于糖尿病非肾病组(P<0.05).(2)4G/4G基因型者PAI-1活性明显高于4G/5G和5G/5G者(P<0.005).(3)糖尿病肾病组PAI-1 4G/4G基因型频率(39%)和4G等位基因频率(60.5%)高于糖尿病非肾病组(33%和56.5%),但无统计学意义(P>0.05).结论 PAI-1活性升高是糖尿病肾病的独立危险因素,PAI-1基因启动子区4G/5G多态性与PAI-1活性密切相关,4G/4G基因型可能是易发糖尿病肾病的遗传标记. 相似文献
8.
Jeng JR 《Cardiology》2007,107(1):30-37
BACKGROUND: Reduced adiponectin level has been associated with metabolic syndrome, type 2 diabetes, coronary artery disease and gene polymorphisms, but the interrelationships of T94G genotype, plasma adiponectin and plasminogen activator inhibitor-1 (PAI-1) are less understood. PATIENTS AND METHODS: The T94G genotypes and plasma levels of adiponectin, and PAI-1 were determined in 568 Chinese patients, 212 with and 356 without hypertension, to study the possible associations of T94G genotype, plasma adiponectin, PAI-1 and blood pressure. RESULTS: Hypertensive patients showed significantly lower plasma adiponectin (9.7 +/- 11.1 vs. 11.5 +/- 10.0 microg/ml, p = 0.04) and higher PAI-1 (p < 0.001) levels but not significantly greater adiponectin TT genotype percentage (38.7 vs. 33.5%) and T allele frequency (0.620 vs. 0.585) than normotensive subjects. Plasma adiponectin was inversely related to PAI-1 activity (r = -0.09, p = 0.03) and antigen (r = -0.202, p < 0.001). Furthermore, the TT genotypic group showed significantly lower plasma adiponectin level (10.4 +/- 10.5 vs. 13.4 +/- 10.8 mug/ml, p = 0.03) and higher plasma PAI-1 activity (17.0 +/- 9.7 vs. 13.5 +/- 7.6 IU/ml, p = 0.003) and antigen (32.3 +/- 22.7 vs. 25.9 +/- 14.7 ng/ml, p = 0.01) than the GG genotypic group. Multiple linear regression analysis in all study subjects, in men and in normotensives documented an impact of adiponectin T94G genotype on plasma levels of adiponectin (p = 0.007, 0.003 and 0.03) and PAI-1 activity (p = 0.02, 0.03 and 0.04) and antigen (p = 0.03, 0.007 and 0.04) after adjustment for potential confounding factors. CONCLUSIONS: The present study demonstrated a significant correlation of the TT genotype with lower plasma adiponectin and higher plasma PAI-1 levels in a Chinese population. The contribution of this genotype seemed greater in men and normotensives. It suggested the adiponectin gene T94G polymorphism might affect the regulation of circulating adiponectin and PAI-1. 相似文献
9.
Enzyme-to-enzyme channeling in the early steps of glycolysis in rat pancreatic islets 总被引:3,自引:0,他引:3
+49 A/G polymorphism of CTLA-4 gene has been suggested to be associated with type 1 diabetes in some populations. However,
a functional significance of the +49 A/G polymorphism is unknown, because it is believed the polymorphism does not affect
the function of the CTLA-4 molecule. In this study, we examined the +49 A/G polymorphism of the CTLA-4 gene in 30 Japanese
type 1 diabetic patients (14 type 1B and 16 type 1A) and 40 non-diabetic subjects in a case-control study, and stratified
patients according to genotype of the polymorphism. The distribution of genotype frequencies differed between type 1 diabetic
patients and controls (p<0.01). When the subjects were subdivided into type 1A and type 1B subgroups, a significant difference in G allele frequency
was found only between type 1B patients and controls, whereas G allele frequency tended to be higher in type 1A diabetic patients
than controls. Type 1B patients displayed more severe metabolic decompensation (higher plasma glucose concentration, lower
urinary C-peptide levels, higher insulin requirement, and higher serum amylase levels), and were found to be more prone to
diabetic ketoacidosis than type 1A patients. After stratification by genotype, differences in urinary C-peptide and serum
amylase levels between type 1A and type 1B patients were found to be due to differences in the GG genotype subgroup, whereas
in the AG subgroup those differences disappeared. In conclusion, the +49 A/G polymorphism of CTLA-4 gene was associated with
the occurrence of type 1B diabetes in a Japanese population, and type 1B diabetics with a GG genotype were associated with
more severe cell dysfunction than their type 1A counterparts. 相似文献
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11.
A polymorphism in the adiponectin gene influences adiponectin expression levels in visceral fat in obese subjects 总被引:2,自引:0,他引:2
Fredriksson J Carlsson E Orho-Melander M Groop L Ridderstråle M 《International journal of obesity (2005)》2006,30(2):226-232
OBJECTIVE: Reduced serum adiponectin levels have been found in obesity and type 2 diabetes and variations in the adiponectin gene (APM1) have been associated with type 2 diabetes and features of the metabolic syndrome in different populations. STUDY DESIGN: Here, we investigated the expression of APM1 in adipose tissue and studied the relationship between variation in APM1 expression, the APM1 G276T polymorphism, the common PPARG Pro12Ala polymorphism and clinical features of 36 morbidly obese (body mass index (BMI) 41.5 +/- 4.9 kg/m2) nondiabetic subjects. RESULTS: APM1 mRNA expression in visceral fat was correlated with serum adiponectin levels (r = 0.54, P = 0.012). In visceral, but not in subcutaneous, adipose tissue APM1 mRNA level was 38% higher among carriers of the APM1 G276T T allele (G/T and T/T) than among carriers of the G/G genotype (0.91 +/- 0.06 for G/T and T/T carriers vs 0.66 +/- 0.09 for G/G carriers, P = 0.013). Carriers of the T allele also had significantly higher body fat percent compared to G/G carriers (65 +/- 6 vs 56 +/- 10%, P = 0.011).Conclusion:Our results indicate that genetic variation in APM1 influences the expression of the gene in visceral adipose tissue and suggest a potential role for such variation in regulation of body fat accumulation in obese subjects. 相似文献
12.
G Hasegawa H Obayashi K Kamiuchi M Nakai T Kanatsuna M Yamaguchi T Tanaka H Shigeta M Fujii T Yoshikawa N Nakamura 《Experimental and clinical endocrinology & diabetes》2003,111(3):132-138
The T/T genotype of the methylenetetrahydrofolate reductase C677 T gene polymorphism is associated with elevated homocysteine levels and presumably with increased atherosclerotic risk. We evaluated the interaction between this gene polymorphism and end-stage diabetic nephropathy on the observed prevalence of macroangiopathy in type 2 diabetes mellitus. The methylenetetrahydrofolate reductase 677 C/T genotypes were determined in 174 type 2 diabetic patients: 80 with and 94 without renal failure due to diabetic nephropathy. In the patients with renal failure, the T/T genotype and T allele were significantly associated with macroangiopathy (T/T; 31 % vs. 2 %, P = 0.0001 T allele; 59 % vs. 29 %, P = 0.00014), whereas the associations were not significant in the patients without renal failure. In the multiple logistic regression analysis, age (10 years OR 4.05 [1.79 - 9.31], P < 0.0005) and 677 T allele (6.84 [2.12 - 22.05], P = 0.0013) were significantly associated with macroangiopathy in the patients with renal failure. In conclusion, this study demonstrated that the 677 T/T genotype and T allele of MTHFR were significantly associated with macroangiopathy in type 2 diabetic patients with renal failure. The MTHFR 677 T allele, together with renal dysfunction due to diabetic nephropathy, could be a strong risk factor for atherosclerotic disease. 相似文献
13.
福建地区2型糖尿病患者脂联素基因启动子区多态性与颈动脉内膜中层厚度有关 总被引:4,自引:3,他引:1
目的 探讨脂联素基因启动子区-11377位点单核苷酸多态性与2型糖尿病患者颈动脉内膜中层厚度(CIMT)之间的关系.方法 采用PCR-限制性片段长度多态性(RFLP)技术在504例2型糖尿病患者(CIMT正常组254例,CIMT增厚组250例)中检测脂联素基因-11377位点多态性,同时检测血脂、空腹血糖、空腹胰岛素及血清脂联素水平.结果 脂联素基因-11377C→G基因型和等位基因频率在CIMT正常组与CIMT增厚组的分布有显著性差别(P相似文献
14.
Abdol Rahim NikzamirTaghi GolmohammadiManouchehr NakhjavaniMahine ZahraeiAli Akbar Amirzargar 《Iranian journal of immunology : IJI》2006,3(1):23-29
Background: Angiotensin I converting enzyme (ACE) is a Zinc metalloproteinase, converts Ang-I to Ang- II, a pro-inflammatory agent which may contribute to pathophysiology of some diseases like type 2 diabetes. Objective: To investigate the relationship between ACE I/D polymorphism and type 2 diabetes in 261 Iranian casecontrol pairs. Methods: 170 patients (85 type 2 diabetics with nephropathy and 85 type 2 diabetics without nephropathy) and 91 healthy control subjects were enrolled in our study. I/D polymorphism of the ACE gene was detected by polymerase chain reaction (PCR) utilizing specific primers. Results: The frequency of DD genotype in the DN group was higher than that of the type 2 diabetic patients (30.6% vs. 20%, P =0.157) and the control group (30.6% vs. 14.3%, P=0.006). The frequency of D allele in nephropathic patients was 58.2% as compared to type 2 diabetic patients without nephropathy 50.5% (P=0.19) and control subjects 37.3% (P =0.001). Therefore, the frequency of DD genotype and D allele significantly increased in DN patients in comparison to healthy controls. Conclusion: It is concluded that the DD genotype and/or D allele of ACE gene may increase the risk for type 2 diabetes but not diabetic nephropathy. 相似文献
15.
Genetic association study of adiponectin polymorphisms with risk of Type 2 diabetes mellitus in Korean population. 总被引:7,自引:0,他引:7
Y Y Lee N S Lee Y M Cho M K Moon H S Jung Y J Park H J Park B S Youn H K Lee K S Park H D Shin 《Diabetic medicine》2005,22(5):569-575
AIMS: To investigate any association between Type 2 diabetes mellitus and two single nucleotide polymorphisms (SNPs) in the adiponectin gene, T45G and G276T, in the Korean population. METHODS: We genotyped 427 non-diabetic controls and 493 Type 2 diabetic patients for SNPs T45G and G276T of adiponectin gene, measured plasma adiponectin concentrations, and examined clinical parameters in Koreans. RESULTS: There were no statistically significant differences in allele frequencies of SNPs 45 and 276 comparing control with Type 2 diabetic subjects (T frequency 68.3% vs. 71.6%, P=0.13 for SNP45, G frequency 72.2% vs. 68.9%, P=0.12 for SNP276). The genotype distributions of these SNPs had no association with the risk of Type 2 diabetes and metabolic parameters of insulin resistance. Plasma levels of adiponectin were not statistically different according to T45G and G276T either, in both control and Type 2 diabetic subjects. CONCLUSION: The T45G and G276T of the adiponectin gene may not be an important determinant of Type 2 diabetes or insulin resistance in Korean subjects. 相似文献
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目的 探讨甘肃地区PRKAA2基因rs2746342(G/T)单核苷酸多态性与T2DM及血清脂联素(APN)、抵抗素(Resistin)的关系。方法甘肃地区T2DM患者163例和正常对照组86名,两组年龄、性别匹配,采用聚合酶链反应/DNA限制性片段长度多态性(PCR/RFLP)、酶联免疫分析(ELISA)检测其基因多态性、空腹C肽(FC-P)、APN、Resistin,同时测身高、体重、血压、BMI、空腹血糖、血脂等。结果(1)T2DM组与正常对照组的基因型和等位基因频度分布存在显著差异(P〈0.05);(2)T2DM组各基因型T/T、G/T、G/G中Resistin、TG、TC、LDL-C、FC-P依次降低,APN、HDL-C依次增高(P〈0.05);(3)APN水平在糖尿病超重组低于糖尿病正常体重组和对照组,Resistin水平在糖尿病超重组高于糖尿病正常体重组和对照组(P〈0.05);(4)相关分析表明APN水平与BMI、血压负相关,与C-肽正相关(P〈0.05),Resistin水平与BMI、血压正相关,与G肽负相关(P〈0.05);(5)T2DM超重组较T2DM正常体重组和正常对照组TG、LDL-C水平升高(P〈0.05),HDL-C水平降低(P〈0.05)。结论甘肃地区PRKAA2基因rs2746342(G/T)单核苷酸基因多态性可能与T2DM及胰岛素抵抗、血清APN、Re—sistin水平关联。 相似文献
18.
目的 探讨单核细胞趋化蛋白-1(MCP-1)基因-2518A/G多态性与老年2型糖尿病患者并发肾功能衰竭之间的相关性.方法 采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法检测56例2型糖尿病伴肾功能衰竭患者及56例2型糖尿病(无肾损伤)患者、50名健康对照者的MCP-1基因-2518位点的基因型分布及基... 相似文献
19.
基质金属蛋白酶9基因多态性与2型糖尿病血管病变的相关性研究 总被引:12,自引:0,他引:12
目的 探讨基质金属蛋白酶9(MMP-9)基因C-1562T多态性与2型糖尿痫血管病变的关系.方法 运用PCR-RFLP检测110名健康对照者和450例2型糖尿病(DM)患者(其中单纯2型DM者100例、大血管病变者120例、糖尿病肾病(DN)患者130例、糖尿病视网膜病变患者100例)的MMP-9基因型,比较各组的基因型和等位基因频率。结果 (1)所有糖尿病视网膜病变患者的基因型均为CC型。(2)与对照组和单纯2型DM组相比,大血管病变组的T基因型和T等位基因频率显著升高,而DN组的TT基因型和T等位基因频率明显下降。(3)Logistic回归分析显示MMP-9 T等位基因、血清MMP-9、总胆固醇、低密度脂蛋白胆固醇、脂蛋白(a)是大血管病变发生的危险因素;尿白蛋白排泄率、脂蛋白(a)、HbA1C是DN发生的危险因素。结论 MMP-9基因C-1562T多态性与2型DM血管病变的发生有关,T等位基因是大血管病变的易感基因,是DN的保护基因。 相似文献
20.
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 总被引:4,自引:0,他引:4
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。 相似文献