SUMO4基因多态性与2型糖尿病的关系

为了探讨北京汉族人群小泛素样修饰蛋白4(Small ubiquitin-like modifier 4, SUMO4)基因多态性与2型糖尿病(Type 2 diabetes mellitus, T2DM)的关系, 文章采用病例对照设计, 选取404例T2DM患者(T2DM组)以及年龄、性别匹配的500例健康对照者(Control组)作为研究对象, 应用聚合酶链反应-高分辨熔解曲线(PCR-HRM)技术结合测序验证法, 检测SUMO4基因3个单核苷酸多态性位点(rs237025、rs237024及rs600739)的基因型与等位基因分布情况, 比较T2DM组糖化血红蛋白(Hemoglobin A_1c, HbA_1c)在各基因型间的分布, 并进行单倍型分析。结果显示：①rs237025的G等位基因在T2DM组出现的频率更高(0.334 vs. 0.282, P =0.017); GA基因型携带者患T2DM的风险是AA基因型携带者的1.563倍(P=0.001; OR, 1.563; 95% CI, 1.189-2.053); 在显性模型(GG+GA vs. AA)分析中, G等位基因携带者(GG+GA)患T2DM的风险是AA基因型携带者的1.525倍(P =0.002; OR, 1.525; 95% CI, 1.169-1.989)。而rs237024和rs600739多态性未发现与T2DM的易感性相关(P >0.05)。②在T2DM组, rs237025的G等位基因携带者、rs237024的TT基因型携带者及rs600739的GG基因携带者具有较高的HbA_1c水平, 但各基因型携带者之间HbA_1c水平并无统计学差异(P >0.05)。③单倍型AAC、AGC及GGT与T2DM的易感性正相关(OR>1); 而单倍型AAT、GAC与T2DM的易感性负相关(OR<1)。据此得出结论：rs237025多态性与北京汉族人群T2DM的易感性相关, rs237024和rs600739多态性可能与T2DM的易感性不相关。     

PPARGC1A基因Thr394Thr/Gly482Ser多态性与2型糖尿病的关联研究

对344例2型糖尿病患者和307名正常人的PPARGC1A基因单核苷酸多态性rs2970847(Thr394Thr)和rs8192678(Gly482Ser)与2型糖尿病的关系进行了单标记和单体型关联分析以及Logistic回归分析。在单标记分析中,对照组与病例组Thr394Thr的基因型和等位基因频率有显著差异(基因型, P =0.006; 等位基因, P < 0.001); Logistic回归和单体型分析表明, Thr394Thr的AA基因型及Thr394(ACA)-Ser482单体型增加患2型糖尿病的风险。Gly482Ser的基因型和等位基因频率在对照组与病例组间无显著差异。PPARGC1A基因是湖北汉人的一个2型糖尿病易感基因。     

诱导型一氧化氮合酶基因多态性与2型糖尿病关系研究

目的:观察诱导型一氧化氮合酶(iNOS)基因Ser608Leu位点基因多态性与2型糖尿病的相关性。方法:采用测序法测定261例2型糖尿病患者和128例正常对照者iNOS基因Ser608Leu位点基因多态性。结果:两组间iNOS基因Ser608Leu位点基因型及等位基因频率构成存在差异。结论:iNOS基因Ser608Leu位点多态性与2型糖尿病有关。     

诱导型一氧化氮合酶基因多态性与2型糖尿病关系研究

目的：观察诱导型一氧化氮合酶（iNOs）基因Ser608Leu位点基因多态性与2型糖尿病的相关性。方法：采用测序法测定261例2型糖尿病患者和128例正常对照者iNOS基因Ser608Leu位点基因多态性。结果：两组间iNOS基因Ser608Leu位点基因型及等位基因频率构成存在差异。结论：iNOS基因Ser608Leu位点多态性与2型糖尿病有关。     

Calpain10基因多态性与2 型糖尿病的相关性研究

目的：探讨钙蛋白酶10（Calpain10）基因第3内含子SNP19多态性在湖北汉族人群2型糖尿痛发生发展中的作用。方法：采用同胞对（家系内对照）和随机病例-对照两种实验设计,结合聚合酶链反应-限制性片断长度多态性（PCR-RFLP）．技术分析共403个样本的Calpain10基因第3内合子SNP19多态性,并测定身高、体重、腰围、臀围、血压和空腹血糖等生理指标。结果：两种实验设计中对照组与病例组的基因型和基因频率均无显著差异（PO．05）。结论：Calpain10基因SNP19多态性在湖北汉族人群2型糖尿病的发生发展中可能不起主要作用。     

胰岛素受体基因多态性与2 型糖尿病的相关性

目的：探讨胰岛素受体基因（INSR）的第8外显子NaiⅠ多态性与湖北汉族人群2型糖尿痛的相关性;方法：采用同胞对（家系内对照）和随机病例-对照两种实验设计,并结合聚合酶链反应-限制性片断长度多态性（PCR—RFLP）技术分析了224个样本的INSR基因第8外显子NsiⅠ多态性,并洲定了身高、体重、腰围、臀围、血压和空腹血糖等生理指标;结果：两种实验设计中对照组与病例组的基因型和基因频率均无显著差异;结论：INSR基因在湖北汉族人群2型糖屎病的发生发展中可能不起主要作用。     

ApoE基因多态性与2型糖尿病并发症的研究进展

2型糖尿病(T2DM)及其并发症的发生与发展与ApoE基因的多态性存在密切关系。本文从ApoE基因与脂代谢、ApoE基因与T2DM、ApoE基因T2DM并发症的关系讨论了ApoE基因多态性在T2DM及其并发症在发病方面的机制,为临床治疗T2DM及其并发症提供了理论基础。     

载脂蛋白E基因多态性与2型 糖尿病脑梗死的关系

研究载脂蛋白E (ApoE) 基因多态性与中国东北汉族2型糖尿病合并脑梗死的关系。采用聚合酶链反应－限制性片段长度多态性（PCR-RFLP）技术,检测了208例个体的ApoE基因多态性,其中对照（CON）组69例,2型糖尿病无大血管病变（T2DM）组67例和2型糖尿病合并脑梗死（T2DMCI）组72例;同时测定了其中70例T2DMCI患者的血脂含量。CON组等位基因频率为：ε2 9.6％、ε3 82.4％、ε4 8.1％,基因型频率为：ε2ε3 13.2％、ε3ε367.6％、ε3ε416.2％;T2DM组等位基因频率为：ε2 10.5％、ε3 84.3％、ε4 5.2％,基因型频率为：ε2ε3 19.4％、ε3ε370.1％、ε3ε49％;T2DMCI组等位基因频率为：ε2 11.8％、ε3 84.7％、ε4 3.5％,基因型频率为：ε2ε3 15.2％、ε3ε375％、ε3ε44.2％。3组间等位基因和基因型频率的差异经检验无统计学意义。T2DMCI患者中各基因型之间的血浆总胆固醇 （TC）、甘油三酯 （TG）、高密度脂蛋白胆固醇（HDL-C）和低密度脂蛋白胆固醇（LDL-C）水平亦无显著性差异。在中国东北汉族人群中,未发现ApoE基因多态性与T2DMCI之间存在关联,亦未发现ApoE基因多态性与T2DMCI患者的TC、TG、 HDL-C和 LDL-C水平之间存在关联。Abstract: In order to explore the association of apolipoprotein E (ApoE) gene polymorphism with cerebral infarction in type 2 diabetic patients of Han nationality in Northeast China , the genotypes of ApoE gene were analyzed by polymerase chain reaction –restriction fragment length polymorphism (PCR-RFLP) in the 208 cases, including 69 cases in control (CON) group and 67 in type 2 diabetes mellitus (T2DM) group as well as 72 in type 2 diabetes mellitus with cerebral infarction (T2DMCI) group. Plasma lipid content in T2DMCI was also detected for 70 cases. The distribution of genotypes in ApoE gene,ε2ε3、ε3ε3 as well asε3ε4 was no significant difference in three groups (ε2ε3 : 13.2％、ε3ε3 : 67.6％、ε3ε4 : 16.2％in CON group;ε2ε3 : 19.4％、ε3ε3: : 70.1％ε3ε4 : 9％in T2DM group;ε2ε3 : 15.2％、ε3ε3 : 75％、ε3ε4 : 4.2％in T2DMCI group).The allele frequencies ofε2、ε3 andε4 were not significantly different in the three groups, either (ε2 : 9.6％、ε3 : 82.4％、ε4 : 8.1％in CON group; ε2 :10.5％、ε3 :84.3％、ε4 : 5.2％in T2DM group; ε2 :11.8％、ε3 :84.7％、ε4 : 3.5％in T2DMCI group). The levels of total cholesterol (TC), tryglyceride (TG), high density lipoprotein-cholesterol (HDL-C) and low density lipoprotein-cholesterol (LDL-C) were not significantly different among the different genotypes in T2DMCI group. The study confirmed that the polymorphisms of ApoE gene are neither associated with the T2DMCI, nor with the levels of plasma lipid in T2DMCI.     

中国汉族人群2型糖尿病易感性相关基因多态性

2型糖尿病（type2 diabetes mellitus,T2DM）的发病与多个基因累加效应及多种环境因素相关。已在中国汉族人群中研究过的与T2DM易感性相关的基因多态性包括：全基因组相关研究中的CDKAL1、CDKN2A／B、SLC30A8、IGF2BP2、HHEX、FTO以及KCNQI基因;脂联素基因;核呼吸因子基因;葡萄糖激酶基因;肿瘤坏死因子α基因等。探索这些易感基因可以为人类治疗T2DM起到极大的推动作用。但至今已明确的基因依然很少,国内外的研究结果不尽相同,尚需进一步地深入研究。     

脂蛋白脂酶基因多态性与2 型糖尿病的相关性研究

目的：探讨脂蛋白脂酶（lipoprotein lipase,LPL）基因PvuⅡ酶切多态性与2型糖尿病的相关性。方法：采用聚合酶链反应-限制性片段长度多态性（PGR-RFLP）方法,分析了156例样本LPL基因第6内含子PvuⅡ多态性（病例组98人。对照组58。其中40个2型糖尿病同胞对,病例组40人,对照组40人）。结果：病例组与对照组的基因型和基因频率均无显著性差异。结论：湖北汉族人群脂蛋白脂酶基因PvuⅡ酶切多态性与2型糖尿病无明显关联。     

Reactive metabolites and antioxidant gene polymorphisms in type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM), by definition is a heterogeneous, multifactorial, polygenic syndrome which results from insulin receptor (IR) dysfunction. It is an outcome of oxidative stress caused by interactions of reactive metabolites (RMs) with lipids, proteins and other molecules of the human body. Production of RMs mainly superoxides (•O₂⁻) has been found in a variety of predominating cellular enzyme systems including nicotinamide adenine dinucleotide phosphate oxidase, xanthine oxidase, cyclooxygenase, endothelial nitric oxide synthase (eNOS) and myeloperoxidase. The four main RM related molecular mechanisms are: increased polyol pathway flux; increased advanced glycation end-product formation; activation of protein kinase C isoforms and increased hexosamine pathway flux which have been implicated in glucose-mediated vascular damage. Superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase and NOS are antioxidant enzymes involved in scavenging RMs in normal individuals. Functional polymorphisms of these antioxidant enzymes have been reported to be involved in the pathogenesis of T2DM. The low levels of antioxidant enzymes or their non-functionality results in excessive RMs which initiates stress related pathways thereby leading to IR and T2DM. An attempt has been made to review the role of RMs and antioxidant enzymes in oxidative stress resulting in T2DM.     

HHEX gene polymorphisms and type 2 diabetes mellitus: A case-control report from Iran

Genome-wide association studies indicated that hematopoietically-expressed homeobox (HHEX) gene is a remarkable candidate for type 2 diabetes (T2D) mellitus susceptibility in spite of the fact that the results are ambiguous in some cases. So, this study aimed to evaluate the possible correlation between HHEX gene polymorphisms and T2D development in a sample of the Iranian population. The rs1111875G/A, rs7923837A/G, and rs5015480C/T HHEX gene polymorphisms were genotyped in 250 cases and 250 matched (age and sex) healthy controls using tetra-amplification-refractory mutation system-polymerase chain reaction method. The finding revealed the all measured inheritance models of rs1111875G/A and of rs5015480C/T variants dramatically increase the risk of T2D while another polymorphism (rs7923837A/G) was not associated with risk/protective role in T2D. The results indicated that rs1111875G/A and rs5015480C/T may contribute to the enhancement of T2D risk in a sample of the southeast Iranian population.     

Association between FABP2 Ala54Thr polymorphisms and type 2 diabetes mellitus risk: a HuGE Review and Meta‐Analysis

Many studies have examined the association between the FABP2 (rs1799883) Ala54Thr gene polymorphism and type 2 diabetes mellitus risk (T2DM) in various populations, but their results have been inconsistent. To assess this relationship more precisely, A HuGE review and meta‐analysis were performed. The PubMed and CNKI database was searched for case‐control studies published up to April 2014. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated. Ultimately, 13 studies, comprising 2020 T2DM cases and 2910 controls were included. Overall, for the Thr carriers (Ala/Thr and Thr/Thr) versus the wild‐type homozygotes (Ala/Ala), the pooled OR was 1.18 (95% CI = 1.04–1.34, P = 0.062 for heterogeneity), for Thr/Thr versus Ala/Ala the pooled OR was 1.17 (95% CI = 1.05–1.41 P = 0.087 for heterogeneity). In the stratified analysis by ethnicity, the significantly risks were found among Asians but not Caucasians. This meta‐analysis suggests that the FABP2 (rs1799883) Ala54Thr polymorphisms are associated with increased susceptibility to T2DM risk among Asians but not Caucasians.     

European versus Asian differences for the associations between paraoxonase‐1 genetic polymorphisms and susceptibility to type 2 diabetes mellitus

Many studies have examined the associations between paraoxonase‐1 (PON1) genetic polymorphisms (Q192R, rs662 and L55M, rs854560) and the susceptibility to type 2 diabetes mellitus (T2DM) across different ethnic populations. However, the evidence for the associations remains inconclusive. In this study, we performed a meta‐analysis to clarify the association of the two PON1 variants with T2DM risk. We carried out a systematic search of PubMed, Embase, CNKI and Wanfang databases for studies published before June 2017. The pooled odds ratios (ORs) for the association and their corresponding 95% confidence intervals (CIs) were calculated by a random‐ or fixed‐effect model. A total of 50 eligible studies, including 34 and 16 studies were identified for the PON1 Q192R (rs662) and L55M (rs854560) polymorphism, respectively. As for the PON1 Q192R polymorphism, the 192R allele was a susceptible factor of T2DM in the South or East Asian population (OR > 1, P < 0.05) but represented a protective factor of T2DM in European population (OR = 0.66, 95% CI = 0.45–0.98) under a heterozygous genetic model. With regard to the PON1 L55M polymorphism, significant protective effects of the 55M allele on T2DM under the heterozygous (OR = 0.77, 95% CI = 0.61–0.97) and dominant (OR = 0.80, 95% CI = 0.65–0.99) genetic models were found in the European population, while no significant associations in the Asian populations under all genetic models (P > 0.05). In summary, by a comprehensive meta‐analysis, our results firmly indicated that distinct effects of PON1 genetic polymorphisms existed in the risk of T2DM across different ethnic backgrounds.     

Association of vitamin D receptor BsmI gene polymorphism with the risk of type 2 diabetes mellitus

Abstract

Relationship between vitamin D receptor (VDR) BsmI (rs1544410) gene polymorphism and the type 2 diabetes mellitus (T2DM) susceptibility is still conflicting at present. This meta-analysis was conducted to assess the association between VDR BsmI gene polymorphism and the risk of T2DM. The association studies were identified from PubMed, and Cochrane Library on 1 January 2014, and eligible investigations were included and synthesized using meta-analysis method. Eleven reports were recruited into this meta-analysis for the association of VDR BsmI gene polymorphism with T2DM susceptibility. In overall populations, B allele, BB genotype and bb genotype were not associated with T2DM risk. VDR BsmI gene polymorphism was also not associated with the T2DM risk in Asians and Caucasians. In conclusion, VDR BsmI gene polymorphism was also not associated with T2DM risk in overall populations, Asians and Caucasians. However, more studies should be conducted to confirm it.     

The future of protein biomarker research in type 2 diabetes mellitus

Introduction: The onset of type 2 diabetes mellitus (T2DM) is strongly associated with obesity and subsequent perturbations in immuno-metabolic responses. To understand the complexity of these systemic changes and better monitor the health status of people at risk, validated clinical biomarkers are needed. Omics technologies are increasingly applied to measure the interplay of genes, proteins and metabolites in biological systems, which is imperative in understanding molecular mechanisms of disease and selecting the best possible molecular biomarkers for clinical use.

Areas covered: This review describes the complex onset of T2DM, the contribution of obesity and adipose tissue inflammation to the T2DM disease mechanism, and the output of current biomarker strategies. A new biomarker approach is described that combines published and new self-generated data to merge multiple -omes (i.e. genome, proteome, metabolome etc.) toward understanding of mechanism of disease on the individual level and design multiparameter biomarker panels that drive significant impacts on personalized healthcare.

Expert commentary: We here propose an approach to use cross-omics analyses to contextualize published biomarker data and better understand molecular mechanisms of health and disease. This will improve the current and future innovation gaps in translation of discovered putative biomarkers to clinically applicable biomarker tests.