Transcription factor 7-like 2 (TCF7L2) gene polymorphism rs7903146 is associated with stroke in type 2 diabetes patients with long disease duration

Associations between TCF7L2 SNP and diabetic complications and diabetes-related factors were investigated. Subjects with rs7903146 variant had significantly higher prevalence of stroke (24.1% vs. 11.1%; P = 0.039) among subjects exhibiting a long disease duration (≥10 years). In conclusion, the TCF7L2 SNP variant may confer a higher risk of stroke in diabetic patients.     

衰老和肥胖与糖尿病的关系

目的 探索随年龄增长、肥胖程度与糖尿病患病率的关系。方法 对“九五”攻关糖尿病研究数据库中25896名40—99岁研究对象的年龄、肥胖、糖尿病(DM)和糖耐量低减(IGT)等相应数据进行了相关分析。按wHO(1999)标准对数据库中IGT和DM患者进行分类，按中国标准(2002)对数据库中全身性超重[体重指数(BMI)≥24]、肥胖(BMI≥28)、腹部肥胖(男，wC≥85cm；女，wC≥80cm)及腰臀肥胖(wHR≥0．93)患者进行分类。结果 (1)DM患病率与年龄增长(男：R^2＝0．99，女：R^2＝0．91)和IGT(男：R^2＝0．96，女：R^2＝0．96)呈正相关。(2)DM患病率与超重(男：R^2＝0．23，女：R^2＝0．88)、肥胖(男：R^2＝0．96，女：R^2＝0．99)和腹部肥胖(男：R^2＝0．82，女：R^2＝0．74)呈正相关；IGT患病率与腹部肥胖(男：R^2＝0．98，女：R^2＝0．98)呈正相关。BMI、wC、wHR三项指标组合与DM／IGT患病率呈正相关。(3)BMI随年龄增长而下降，wC、wHR随年龄增长而上升。(4)随年龄增长肥胖程度增加可明显增加DM／IGT患病率。结论 衰老、BMI、腹部肥胖与DM和IGT患病率增长有明显的相关关系。衰老同时伴全身和腹部肥胖可加大DM和IGT的患病风险。     

TCF7L2基因多态性与合肥地区人群2型糖尿病的关联性研究

探讨TCF7L2基因多态性与合肥地区人群2型糖尿病遗传易感性的关系.结果 显示TCF7L2基因的微卫星(DG10S478)多态性与合肥地区人群2型糖尿病发病风险无明显相关(P>0.05),在该地区人群2型糖尿病的发病中并非主效基因.     

Association of Kir6.2 gene rs5219 variation with type 2 diabetes: A meta-analysis of 21,464 individuals

Aims

rs5219 is in Potassium inwardly-rectifying channel, subfamily J, member 11 (KCNJ11) E23K gene, located at 11p15.1. Researches on the association between rs5219 gene polymorphism with type 2 diabetes mellitus (T2DM) were performed extensively, but the results remain controversial. To investigate the relationship, a meta-analysis involving 21,464 individuals was conducted.

TCF7L2基因单核苷酸多态性与妊娠期糖尿病的相关性研究

目的 探讨转录因子7类似物2(TCF7L2)基因rs290487、rs11196205、rs11196218位点单核苷酸多态性(SNP)与妊娠期糖尿病(GDM)的关系.方法 采用病例对照研究方法,选取中国北方地区无血缘关系的糖耐量受损(IGT)孕妇158例、GDM孕妇335例作为病例组,正常妊娠妇女647例作为对照组.提取所有受试者基因组DNA,用连接酶检测反应(LDR)分析TCF7L2基因rs290487、rs11196205、rs11196218位点基因型,并进行相关分析.结果 在rs290487位点,C等位基因频率在病例组为41.6%,明显高于对照组的36.3%(P=0.012).病例组中CC基因型频率为18.7%,明显高于对照组的14.0%(P=0.033).CC基因型GDM发病风险与CT+TT基因型相比,比数比(OR)为1.418(95%CI 1.028～1.955),经logistic回归校正混杂因素后,OR值为1.518(95%CI 1.064～2.166).结论 TCF7L2基因rs290487位点SNP可能在GDM遗传易感性中起重要作用,CC基因型可能是其发生的危险因素.

Abstract：

Objective To investigate the relationship between gene polymorphism of transcripion factor 7-like 2 (TCF7L2) at positions rs290487, rs11196205, rs11196218 and gestational diabetes mellitus (GDM) in Chinese women.Methods In 1140 unrelated pregnant Northern Chinese women (335 women with GDM, 158 gestational cases with impaired glucose tolerance and 647 pregnant non-diabetic controls) ,three single nucleotide polymorphisms (rs290487, rs11196205, and rs11196218) in the TCF7L2 gene were genotyped using ligase detection reaction (LDR).In the present study, cases with GDM and impaired glucose tolerance (IGT) were indistinguishable clinically and biochemically, and were combined into case group.Results The frequency of C allele of rs290487 was 41.6% in case group, being significantly higher than that in control group (36.3%, P=0.012).There was significant difference in the frequency of CC genotype between case group and control group (18.7% vs 14.0%, P=0.033).Compared with T allele carriers, CC genotype carriers had a 1.418-fold increased risk of GDM (95% CI 1.028-1.955).After adjusting for age, body mass index, family history of diabetes,systolic blood pressure,and diastolic blood pressure, pregnant women with CC genotype carriers of rs290487 were more prone to hyperglycemia compared with the T allele carriers (OR 1.518, 95% CI 1.064-2.166).Conclusions The TCF7L2 rs290487 variant may contribute to the genetic predisposition to GDM.CC genotype is likely to be associated with an increased risk of GDM in the pregnant Chinese women.     

TCF7L2基因与2型糖尿病

转录因子7类似物2(TCF7L2)常见变异在不同的种族中几乎都与2型糖尿病显著相关.TCF7L2剪接有显著的组织特异性,在2型糖尿病患者的胰岛内TCF7L2 mRNA水平增高.其变异与胰岛素分泌功能减退有关,机制可能是其特异性损害肠促胰素(incretin)如胰高血糖素样肽-1(GLP-1)诱导的胰岛素分泌,也可能因胰岛素原向胰岛素的转换异常,和(或)参与Wnt信号通路的激活而致2型糖尿病.因此对2型糖尿病致病基因TCF7L2基因的研究有助于揭示糖尿病的发病机制、病理生理及为糖尿病的治疗提供新的靶点.     

转录因子7样2与2型糖尿病

转录因子7样2(TCF7L2)基因是2型糖尿病最重要的易感基因之一,其基因变异体与2型糖尿病有强相关性,是目前2型糖尿病多因子遗传学领域中最引人注目的基因之一.这一结果在许多人种中都得以证实,而在我国关于该基因的研究刚刚起步.TCF7L2基因位于染色体10q25,共编码619个氨基酸,其产物是Wnt信号通路中一种转录因子.该因子通过对胰高血糖素样肽-1(GLP-1)水平调节,在糖代谢中起重要作用.另外,该信号通路与胰腺和胰岛的正常发育密切相关.     

The pleiotropic effect of rs7903146 on type 2 diabetes and ischemic stroke: a family-based study in a Chinese population

Journal of Thrombosis and Thrombolysis - The rs7903146, an established genetic variant susceptible to type 2 diabetes (T2D), is also reported to be related to ischemic stroke (IS), though...     

Glucose tolerance and free fatty acid metabolism in adults with variations in TCF7L2 rs7903146

ObjectiveTCF7L2 variant rs7903146 is associated with increased risk for type 2 diabetes. We investigated the effect of TCF7L2 variant rs7903146 and glucose tolerance on free fatty acid (FFA) metabolism.Research Design and MethodsWe recruited 120 individuals, half homozygous for the major CC allele and half homozygous for the minor TT allele at rs7903146; each underwent a 2-h, 75 g oral glucose tolerance test (OGTT). Plasma glucose, insulin and free fatty acid concentrations were measured on blood collected before and during the OGTT.ResultsTotal FFA concentrations and percent FA species during OGTT were not different in CC and TT carriers when males and females were considered together. However, monounsaturated fatty acid (MUFA) concentrations and percentages were greater in TT than CC females during the OGTT. TT carriers with high HOMA-IR had significantly greater fasting FFA concentrations, lower disposition index (DI) and greater AUC of glucose than high HOMA-IR CC carriers, whereas no such differences were observed in the low HOMA-IR group. We found that fasting (826 ± 25 vs. 634 ± 22 μmol/L, P < 0.0001) and OGTT plasma FFA concentrations were greater in IGT than NGT subjects, and the difference remained after adjusting for sex, age, BMI, and genotype. Finally, IGT subjects had greater MUFA concentrations and percentages than NGT subjects during OGTT.ConclusionsDespite similar fasting insulin and glucose, fasting plasma FFA are greater in IGT than NGT adults. Insulin resistance and sex influence plasma FFA responses amongst carriers of the minor T allele of TCF7L2 rs7903146.     

rs3804100、rs3804099及rs2295080基因多态性与黑龙江省2型糖尿病患者并发肺结核关系的研究

目的探究Toll样受体2(Toll-like receptor 2,TLR2)rs3804100、rs3804099位点和哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)rs2295080位点基因多态性与2型糖尿病并发肺结核的关系。方法选择2017年1-9月黑龙江省传染病防治院收治的300例2型糖尿病并发肺结核患者作为观察组,以及同时期在哈尔滨医科大学附属第四医院内分泌科就诊的300例2型糖尿病患者作为对照组。所有患者收集血液提取DNA,用PCR技术对TLR2的rs3804100、rs3804099位点及mTOR的rs2295080位点进行基因多态性检测,并对这3个基因位点多态性与2型糖尿病并发肺结核的关系进行单因素和logistic多因素分析。结果单因素分析结果显示,TLR2的rs3804100位点TT、TC、CC(T:胸腺嘧啶;C:胞嘧啶)基因型在观察组和对照组分布构成比分别为51.3%(154/300)、25.7%(77/300)、23.0%(69/300)和47.0%(141/300)、31.3%(94/300)、21.7%(65/300),差异无统计学意义(χ^2=2.382,P=0.304);TLR2的rs3804099位点TT、TC、CC基因型在观察组和对照组分布构成比分别为53.0%(159/300)、29.7%(89/300)、17.3%(52/300)和54.3%(163/300)、33.0%(99/300)、12.7%(38/300),差异无统计学意义(χ^2=2.759,P=0.252);mTOR的rs2295080位点TT、TG、GG(G:鸟嘌呤)基因型在观察组和对照组分布构成比分别为26.7%(80/300)、67.3%(202/300)、6.0%(18/300)和24.3%(73/300)、66.0%(198/300)、9.7%(29/300),差异无统计学意义(χ^2=2.935,P=0.231)。logistic多因素分析结果显示,TLR2的rs3804100位点TC、CC基因型的OR(95%CI)值分别为1.261(0.591~2.689)和1.284(0.542~3.042),P值分别为0.549和0.569;TLR2的rs3804099位点TC、CC基因型的OR(95%CI)值分别为0.752(0.461~1.227)和0.729(0.430~1.235),P值分别为0.254和0.240;mTOR的rs2295080位点TG、GG基因型的OR(95%CI)值分别为1.789(0.890~3.596)和1.603(0.839~3.063),P值分别为0.103和0.153。结论 TLR2基因rs3804100、rs3804099位点及mTOR的rs2295080位点多态性与黑龙江省2型糖尿病并发肺结核均无相关性。     

Common variant within the FTO gene,rs9939609, obesity and type 2 diabetes in population of Karachi,Pakistan

AimTo determine the effect of genetic variants within the FTO gene (rs9939609) on obesity related traits and type 2 diabetes in South Asian population of Karachi, Pakistan.MethodsA case-control study was conducted at Baqai Institute of Diabetology and Endocrinology (BIDE), Baqai Medical University situated in Karachi. A total of 296 patients with known type 2 diabetes and 198 controls aged greater than and equal to 45 years were recruited. The Anthropometric, clinical and biochemical data was collected on a structured questionnaire. Single nucleotide polymorphism (SNP) in FTO gene was identified by Amplification Refractory Mutation System-Polymerase Chain Reaction (ARMS-PCR). Association between the single nucleotide polymorphism and categorical variables such as type 2 diabetes and obesity category was tested through logistic regression analysis.ResultsWe observed a strong association of the minor allele A at rs9939609 with type 2 diabetes. Significant difference was observed in frequency of FTO genotype when diabetic subjects were compared with controls in co dominant, dominant and recessive models. This association remained significant even after adjusting for body mass index (BMI) and for waist circumference. The frequency of homozygous risk Alleles (AA) was found to be higher in obese & overweight (≥23 kg/m²) and females with central obesity in our study population. The association of FTO variant with BMI and central obesity does not reach to statistical significance.ConclusionIn the study population of South Asian ancestry, variants of the FTO gene predispose to type 2 diabetes, but not entirely through their effect on BMI.     

Interrelationship of the rs7903146 TCF7L2 gene variant with measures of glucose metabolism and adiposity: The NEO study

Background and aims

We investigated the interrelationship of rs7903146-T in TCF7L2 with measures of glucose metabolism and measures of adiposity.