Ghrelin基因多态性与2型糖尿病的相关性

目的探讨ghrelin基因多态性与2型糖尿病之间的关系。方法进行ghrelin基因C408A和G346A的多态性分析,同时进行生化指标和临床参数的检测。结果正常对照组(NGT组)C408A基因型CC、CA、AA的基因型频率分别为75.4%、24.0%及0.6%。2型糖尿病组(DM组)中CC、CA及AA的基因型频率分别为70.8%、28.2%及1.0%。NGT组CC基因型者总胆固醇水平明显高于CA AA基因型者(P<0.05);DM组CC基因型者血尿酸水平明显高于CA AA基因型者(P<0.05)。在所有的受试者中未发现G346A多态性存在。结论Ghrelin基因C408A分布与等位基因频率没有明显的差异;本组人群中未发现ghrelinG346A多态性存在;C408A多态性与总胆固醇和尿酸水平相关。     

神经源分化因子基因多态性与2型糖尿病的关联性研究

目的　探讨神经源分化因子 (neurogenic differentiation factor 1,Neuro D)基因多态性与 2型糖尿病发生的关联性。方法　运用错配聚合酶链反应 -限制性片段长度多态性方法检测了中国湖北地区汉族 32 4例 2型糖尿病 (其中以发病年龄 40岁为界 ,分为早发及晚发两组 )及 12 4名正常对照者 ,Neuro D基因第 45位密码子碱基变异 (GCC→ ACC)。结果　 Neuro D基因在所测人群中未发现有纯合变异者。在早发 2型糖尿病组 ,其 AT基因型频率为 2 6 .8% ,与正常对照组 (10 .5 % )及晚发 2型糖尿病组 (11.6 % )比较 ,差异有显著性 (分别为χ2 =7.85 ,P=0 .0 0 5 ;χ2 =8.81,P=0 .0 0 3) ;Thr45等位基因频率在早发 2型糖尿病组及正常对照组、晚发 2型糖尿病组分别为 13.4%、5 .2 %和 5 .8% ,差异亦有显著性 (χ2 =7.15 ,P=0 .0 0 8;χ2 =8.13,P=0 .0 0 4) ;晚发 2型糖尿病组与正常对照组比较 ,Ala45 Thr基因型频率 (11.6 % vs10 .5 % ,P>0 .0 5 )及等位基因频率 (5 .8% vs 5 .2 % ,P>0 .0 5 )差异不明显 ,Thr45等位基因与早发 2型糖尿病发生相关 (OR=2 .5 2 ,95 % CI:1.42～ 4.49) ;基因型为 AT型的 2型糖尿病患者其空腹血浆 C肽水平较 AA型患者低 ,差异有显著性 (P<0 .0 5 )。结论　 Neuro D基因多态性与早发 2型糖尿     

2型糖尿病家系与尾加压素2基因多态性

目的探讨我国常州地区汉族家系2型糖尿病与尾加压素2(urotensinⅡ,UT-Ⅱ)基因rs228648多态性位点的关系。方法采用家系内外对照的病例对照研究,并设置无家族史的普通病例组,应用聚合酶链反应-限制性片段长度多态性技术,对rs228648(G/A)多态性进行基因分型。结果家系中携带AG和AA基因型者患病风险分别为GG型的1.98(95%可信区间=1.19～3.29)和2.46(95%可信区间=1.39～4.34)倍,家系病例组A等位基因频率高于内对照组及普通病例组(P=0.01)。内对照组A等位基因频率高于外对照组(P=0.001)。内对照组携带AG基因型者的胰岛素抵抗指数、胰岛素敏感指数以及胰岛初期分泌功能指数均高于GG基因型者(P<0.05)。结论rs228648多态性位点变异可能是2型糖尿病的危险因素之一,家系人群该基因变异与其胰岛功能间存在关联。     

Association of FADS2 rs174575 gene polymorphism and insulin resistance in type 2 diabetes mellitus

BackgroundMany risk factors contribute to the pathogenesis of diabetes. Gene and lifestyle factors are considered to be the major contributors. A dietary pattern is attributed to be one of the lifestyle risk factors favoring diabetes. The present study aims to find an association between fatty acid desaturase (FADS) gene polymorphism and glycemic profile in type 2 diabetes mellitus (T2DM).MethodologyA total of 429 subjects were included in the study on the basis of inclusion and exclusion criteria, of which 213 and 216 subjects were diabetic and control, respectively. Body mass index was calculated. Fasting plasma glucose, glycated hemoglobin (HbA1c) and insulin were measured using commercially available kits. rs174575 of FADS2 was selected based on previous publications and identified using the dbSNP database. To compare the biochemical parameters with the genotype, the following three models were used: additive model (CC vs CG vs GG), dominant model (CC + CG vs GG), and recessive model (CC vs CG + GG).Results and DiscussionFBS, HbA1c, insulin, HOMA-IR, and HOMA-B exhibited a high and statistically significant difference between subjects and controls. The three models exhibited a statistically significant difference between FBS, HOMA-IR, and HOMA- B (p<0.05).ConclusionThe distribution of rs174575 genotype differed significantly between the subjects and controls in the present study. The study revealed that genetic variation in FADS2 is an additional facet to consider while studying the risk factors of T2DM.     

Meta-analysis of the effect of HHEX gene polymorphism on the risk of type 2 diabetes

In the past decade, a number of case-control studies have been carried out to investigate the relationship between the HHEX polymorphism and type 2 diabetes (T2D). However, the results have been inconclusive. To investigate this inconsistency, we performed a meta-analysis of all available studies dealing with the relationship between the HHEX polymorphism and T2D. In total, 22 association studies on two HHEX polymorphisms (rs1111875 and rs7923837) and risk of T2D published before April 2010, including a total of 36?695 T2D cases and 51?800 controls were included. We also explored potential sources of heterogeneity. In a combined analysis, the summary per-allele odds ratio (OR) for T2D of the rs1111875 and rs7923837 polymorphism was 1.17 [95% confidence interval (CI): 1.13-1.21] and 1.23 (95% CI: 1.18-1.28), respectively. The haplotype analysis also showed significant association in the pooled international populations with an OR of 1.19 (95% CI: 1.15-1.22). In the subgroup analysis by ethnicity, significantly increased risks were found in Asians and Caucasians for these polymorphisms in almost all genetic models. Subgroup analysis also showed that ethnicity is the main source of heterogeneity between pooled studies. This meta-analysis demonstrated that the risk allele of HHEX polymorphisms (rs1111875 and rs7923837) is a risk factor for developing T2D. However, additional very large-scale studies are warranted to provide conclusive evidence on the effects of the HHEX gene on risk of T2D.     

配对盒4基因Arg121Trg多态性与2型糖尿病的相关性

目的 探讨配对盒4(Pax4)基因Arg121Trg多态性(rs114202595)与云南省昆明地区2型糖尿病的相关性.方法 根据口服75 g葡萄糖耐量试验(OGzTT)将1 076例云南省昆明地区人群分为2型糖尿病组(T2DM)、糖耐量减低组(IGT)和健康对照组(NGT),应用高分辨率熔解曲线分析方法(HRM)检测Pax4基因Arg121Trg基因型,观察3组人群中基因型和等位基因的分布情况,同时分析T2DM人群中不同基因型相关临床变量的差异性.结果 1)Pax4基因Arg121 Trg GG基因型(Arg/Arg)及A等位基因(Trg121)在T2DM组中的频率分别为0.909和0.047,在IGT组中为0.935和0.035,在NGT组中为0.939和0.03.2)T2DM组Arg121Trg 多态性GA+ AA基因型(Arg/Trg+ Trg/Trg)人群胰岛素使用率显著高于GG基因型(Arg/Arg)人群(P=0.001),而其他临床变量在T2DM组中两种基因型人群间比较均无明显差异.结论 Pax4基因Arg121Trg多态性A等位基因可能是云南省昆明地区2型糖尿患者群胰岛β功能进展性紊乱的一个分子标记.     

Mannose binding lectin gene polymorphism in patients with type I diabetes

Our purpose was to investigate a possible relationship between occurrence of type I diabetes and polymorphism of the mannose binding lectin gene. Polymorphism of codon 54 of the mannose binding lectin (MBL) gene, whose presence of the minority allele leads to significant reduction of serum MBL concentration, was investigated in 128 Japanese patients with type I diabetes and 78 healthy volunteers by restriction fragment length polymorphism method. Frequencies of the minority allele were compared between the patient group and the control group. Frequency of the minority allele was 24.2% in the patient group and 19.9% in the control group. The probability of being heterozygous or homozygous for the minority allele was 41.4% in the patient group and 33.3% in the control group. Patients with DRB1*0405-DQB1*0401 and/or DRB1*0901-DQB1*0303 haplotypes, the two major type I diabetes-prone human leukocyte antigen haplotypes, showed a slightly higher probability of being heterozygous or homozygous for allele B of the MBL gene. Possession of the minority allele of the MBL gene may be a minor risk factor for having type I diabetes.     

HLA-DRB基因启动子区多态性与肺结核合并2型糖尿病的相关性

目的研究HLADRB基因启动子区序列与肺结核合并2型糖尿病的相关性。方法用PCRSSP法进行HLADRB基因分型,启动子区扩增产物直接测序。结果病例组DRB109等位基因的频率显著高于对照组(P<0.05)。病例组中DRB基因启动子区-65位碱基T和-8位AG杂合子的频率明显增加(P<0.05)。病例组中DRB109阳性标本-65位碱基T的频率明显增加,G明显减少(P<0.01);+39位碱基C明显增加,T明显减少(P<0.01)。结论DRB109等位基因及HLADRB启动子区多态性与肺结核合并2型糖尿病密切相关。     

A polymorphism in the promoter of UCP2 gene modulates lipid levels in patients with type 2 diabetes

A G/A single nucleotide polymorphism (SNP) in the position -866 of the UCP2 promoter modulates UCP2 expression in adipose tissue and pancreatic beta-cell, and is associated with variations of body mass index (BMI) and insulin secretion in nondiabetic subjects. We investigated associations of this SNP with traits related to obesity, dyslipidemia, and hyperglycemia in patients with type 2 diabetes. The -866 G/A SNP in the UCP2 promoter was genotyped by PCR/RFLP in 681 type 2 diabetic patients. Increased triglyceride (> or = 1.70 mM), total cholesterol (> or = 6.0 mM) and LDL-cholesterol (> or = 3.35 mM) levels were significantly less frequent in homozygous carriers of the G-allele than in homozygous carriers of the A-allele. Odds ratios for the risk of dyslipidemia in GG vs AA carriers were 0.45, 0.57, and 0.50, for triglyceride, total cholesterol and LDL-cholesterol, respectively (all p<0.007). No genetic effects of this polymorphism on the BMI or on traits related to the severity of hyperglycemia were observed. In conclusion, a common polymorphism in the promoter region of the UCP2 gene modulates triglycerides and cholesterol levels in French Caucasian subjects with type 2 diabetes. The implications of this effect in the evolution of type 2 diabetes and its macrovascular complications deserve to be investigated.     

2型糖尿病胰岛素抵抗和胆固醇酯转运蛋白基因多态性的关联研究

目的 探讨胆固醇酯转运蛋白(cholesteyl ester transfer protein，CETP)基因多态性与2型糖尿病胰岛素抵抗的关系。方法 采用聚合酶链反应和酶切电泳方法对108例2型糖尿病患者进行CETP-TaqIB基因型分型，同时测定血脂、空腹胰岛素、胰岛素敏感指数和胰岛素抵抗指数。结果 正常对照组与2型糖尿病组等位基因频率和基因型分布无统计学意义；2型糖尿病甘油三酯(triglyceride，TG)、总胆固醇(total cholesterol，TC)、低密度脂蛋白胆固醇(low density lipoprotein cholesterol，LDL-C)和载脂蛋白B(apolipoprotein B，apoB)浓度各基因型间差异无统计学意义，而高密度脂蛋白胆固醇(high density lipoprotein cholesterol，HDL-C)、载脂蛋白A1(apolipoprotein A1，apoA1)、空腹胰岛素(fasting insulin，FINS)、胰岛素敏感性指数(insulin sensitivity index，ISI)和HOMA模型胰岛素抵抗指数(homeostasis model assessment-insulin resistance，HOMA-IR)各基因型间差异有统计学意义，HDL-C、apoA，和ISI B2B2型显著高于B1B1型，FINS和HOMA-IR B2B2型显著低于B1B1型；以胰岛素敏感性指数和HOMA-模型胰岛素抵抗指数为因变量进行多元回归分析，ISI和HOMA-IR与体重指数、收缩压、TC、HDL及基因型分型密切相关。结论 CETP-Taq IB基因多态性与2型糖尿病脂代谢及胰岛素抵抗密切关联，可能是胰岛素抵抗的重要遗传因素。     

NAT2基因多态性与2型糖尿病的关系

目的探讨NAT2基因多态性与2型糖尿病易感性的关系,为糖尿病的有效防治提供科学依据。方法采用PCR及测序技术对174例2型糖尿病患者和174例健康者的NAT2基因4个常见突变位点进行检测。结果糖尿病组中NAT2等位基因频率分别为：Wt（69.54%）,M2（16.37%）,M3（10.63%）,M1（3.44%）。与正常对照组比较差异无显著性。NAT2基因型（WT/WT,WT/Mx,Mx/Mx）在糖尿病组中分布频率分别为44.82%,49.42%,5.74%,两组间比较差异显著。糖尿病组中快乙酰化者164例（占94.25%）,慢乙酰化者10例（占5.75%）,两组间比较有差异。携带NAT2快乙酰化基因型者患2型糖尿病的风险是携带NAT2慢乙酰化基因型者的3.98倍。结论本研究提示快乙酰化代谢表型可能是糖尿病的一个遗传易感因素,而慢乙酰化代谢表型可能对糖尿病的发生具有一定保护作用。     

2型糖尿病及其肾病与血管生成素2基因多态性的关联分析

目的 研究2型糖尿病(type 2 diabetes mellitus,T2DM)及其肾病(diabetic nephropathy,DN)发生、发展与血管生成素2(angiopoietin-2,Ang-2)基因多态性的关联性.方法 应用等位基因特异聚合酶链反应检验无亲缘关系汉族人群的2型糖尿病及其肾病患者221例、正常对照104名Ang-2基因单核苷酸多态性(single nucleotide polymorphism,SNP)759T/G、1078A/G、1233A/G在病例组中的频率,并用尿白蛋白排泄率、炎症标志物单核细胞趋化蛋白浓度变化探讨上述SNP与T2DM、DN发生发展的关联.结果 (1) Ang-2 759 T/G、1078 A/G基因型频率和等位基因频率在各组中的差异无统计学意义,而1233 A/G基因型频率和等位基因频率的差异有统计学意义(P＜0.05);(2)在校正年龄和性别等因素后,1233A/GSNP G等位基因患T2DM和DN的风险分别是A等位基因的2.265倍(95％ CI:1.223～1.402,P=0.031)和1.789倍(95％ CI:0.889～1.021,P=0.012);(3) Ang-2 1233A/G G等位基因与DN发生相关(r=1.321,OR=1.427,95％ CI:2.324～4.177,P=0.034).结论 Ang-2 1233A/G SNP与2型糖尿病的发生有关;AG+ GG基因型和等位基因G可能是DN发生、发展的风险因素.     

磺脲类受体基因多态性与新疆地区2型糖尿病相关性研究

目的　研究磺脲类受体 (sulfonylureareceptor,SUR1)基因第 2 4内含子 3tc多态性与新疆地区 2型糖尿病的相关性。方法　利用PCR -RFLP法对新疆地区 72例受试者 (2型糖尿病患者 4 2例 ,正常对照 30例 )磺脲类受体基因第 2 4内含子 - 3t→c多态性进行研究。结果　SUR1基因第 2 4内含子“c”等位基因频率在患者及对照中无显著差异 (77 5 %比 6 3 5 % ,P =0 0 6 5 3) ,“cc”基因型频率分别为 6 1 9% ,4 0 % ,也无显著差异 (P =0 0 6 6 2 )。结论　SUR1基因第 2 4内含子 - 3t→c多态性可能在新疆地区 2型糖尿病发病中不起重要作用。     

PPP1R3基因多态性与中国汉族人群2型糖尿病的相关性研究

目的　旨在研究 1型蛋白磷酸酶骨骼肌特异的糖原靶向调节亚单位基因 (PPP1R3)Asp90 5Tyr以及 3′ -UTR5bpD/I多态性与安徽省汉人群的 2型糖尿病 (T2DM )相关性。方法　运用PCR -RFLP法对安徽省合肥地区 36 6例汉族受试者 (T2DM患者 2 6 2例 ,健康成人 10 4例 )进行基因型测定。结果　 (1)PPP1R3基因Asp90 5Tyr以及 3′ -UTR 5bpD/I多态性的基因型及等位基因频率在T2DM与健康对照组间分布均没有显著性差异 (P >0 .0 5 )。 (2 )PPP1R3基因Asp90 5Tyr以及3′ -UTR 5bpD/I多态性间呈连锁不平衡 ,其分布频率在不同人群中不尽相同。结论　PPP1R3基因Asp90 5Tyr以及 3′ -UTR 5bpD/I多态性可能在安徽省合肥地区 2型糖尿病发病中不起重要作用。两种多态性的分布表现明显的种族性。