上游转录因子1基因多态性与代谢综合征研究进展

上游转录因子基因位于染色体上代谢综合征和2型糖尿病连锁分析重现率最高的区域(1q21-q25)内.该基因编码的蛋白属于碱性螺旋-环-螺旋-亮氨酸拉链家族的成员,可参与控制和调节糖、脂代谢相关基因的表达,因而可作为代谢综合征和2型糖尿病的重要候选基因.本文就上游转录因子1基因的结构、生物学特性以及与代谢综合征相关性状关系的研究进展进行了综述.     

延边汉族和朝鲜族人群脂联素基因与2型糖尿病的关联性研究

目的 本研究分析延边汉族和朝鲜族人群中脂联素基因启动子的单核苷酸多态性(SNPs)与2型精尿病的关联.方法 共有97个延边个体被纳入到本研究中,包括55个汉族(13个正常人和42个2型糖尿病患者)和42个朝鲜族(16个正常人和26个2型糖尿病患者).检测项目包括体重指数(BMI)、空腹血糖(FPG)、总胆同醇(TC)和甘油三酯(TC).PCR和测序用于SNP的筛选.ANOVA和χ~2检验用于数据分析.结果 在延边朝鲜族中TG在2型糖尿病组大于正常组(P=0.033).FPG、TC和TC在延边朝鲜族2型糖尿病组大于延边汉族2型糖尿病组(P=0.038;P=0.037;P=0.047).在延边朝鲜族中-11426A-11377C的单体型频率在2型糖尿病组小于正常组(P=0.043).在延边汉族中BMI与-11426位点的基因型有关,基因型-11426G的BMI小于基因型-11426A(P=0.039).-11426位点从基因型的BMI在延边汉族大于延边朝鲜族(P=0.006).结论 1.延边汉族和朝鲜族之间在2型糖尿病组中FPG、TC和TG存在民族差异.2.在延边朝鲜族中单体型-11426A-11377C可能在2型糖尿病发展过程中被认为是一种保护因素.3.在延边汉族中SNP-11426A>G可能与肥胖有关.     

广东汉族人群脂联素基因多态性与2型糖尿病相关性研究

目的探讨脂联素基因外显子2基因多态性与广东地区汉族人群2型糖尿病的关系。方法以聚合酶链式反应-限制性内切酶长度多态性（PCR-RFLP）技术观察200名健康人与200例2型糖尿病基因外显子2基因多态性。结果2型糖尿病组G/G基因型频率明显高于正常对照组（P〈0.01）,G等位基因频率明显高于正常对照组（P〈0.01）,T等位基因频率明显低于正常对照组（P〈0.01）。结论脂联素基因可能是广东地区汉族人群中2型糖尿病的易感候选基因。     

武汉地区原发性高血压代谢综合征与CYP11B2-344T/C基因多态性关系的探讨

目的:探讨武汉地区原发性高血压(EH)代谢综合征(MS)与醛固酮合成酶(CYP11B2)基因-344C/T多态性的关系。方法:701例武汉地区汉族人群分为3组,其中血压正常对照组303例,EH伴MS组189例,EH不伴MS组209例。应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术检测3组人群CYP11B2-344T/C基因多态性。结果:(1)EH不伴MS组CYP11B2基因CC+TC基因型频率明显高于血压正常对照组。(2)CYP11B2TT基因型EH伴MS组的血压水平明显高于其它基因型。结论:EH不伴MS与CYP11B2基因多态性相关;EH伴MS患者血压水平与CYP11B2基因TT基因型明显相关。     

FTO rs8050136多态性与黑龙江地区汉族人群2型糖尿病的相关性

目的探讨FTO基因rs8050136单核苷酸多态性与2型糖尿病（T2DM）的相关性。方法采用病例对照研究：病例组为500例,对照组为500例。利用SNa Pshot方法检测基因型。研究FTO基因rs8050136等位基因、基因型和显性模型与T2DM的关系。结果 FTO基因SNP rs8050136等位基因A与C相比,在T2DM组和对照组间的分布频率有统计学意义（P〈0.05,OR：1.28,95%CI：1.12~1.54）;与CC基因型相比,CA基因型和显性模型CA＋AA在两组间的比较有显著差异（P〈0.05,OR：1.25,95%CI：1.03~1.59;P〈0.05,OR：1.29,95%CI：1.13~1.47）。结论 FTO基因SNP rs8050136增加我省人群患T2DM的风险。     

AQP7和AQP9基因多态性与中国汉族人群2型糖尿病的相关性研究

目的探讨水通道蛋白7(aquaporin 7, AQP7)以及水通道蛋白9(aquaporin 9, AQP9)基因单核苷酸多态性(single nucleotide polymorphism, SNP)与中国汉族人群患2型糖尿病(type 2 diabetes mellitus, T2DM)的相关性。方法随机纳入1194例T2DM个体和1274例非糖尿病个体(non-diabetic, NDM)进行对照研究, 采用MassArray质谱基因分型方法对3个SNP位点(AQP7基因rs3758269、AQP9基因rs16939881和rs57139208)进行基因分型。评估以上3个SNP位点与T2DM的相关性;探讨NDM组SNP位点处不同基因型与糖脂代谢指标的关联。结果 AQP7基因rs3758269、AQP9基因rs16939881和rs57139208的等位基因频率及基因型频率在T2DM组和NDM组中的分布无统计学差异(P > 0.05);且分析结果显示不同遗传模式与T2DM无相关性(P > 0.05)。在NDM组中, AQP7基因rs3758269、AQP9基因rs16939881和rs57139208的不同基因型与糖脂代谢指标无相关性(P > 0.05)。结论 AQP7基因rs3758269和AQP9基因rs16939881和rs57139208与中国汉族人群T2DM遗传易感性无关。     

脂联素基因+45位T/G多态性与2型糖尿病遗传易感性的相关性

目的 研究脂联素基因单核苷酸多态性(SNP)45(T/G)位点与宁夏汉族人群2型糖尿病之间的关系.方法 100例2型糖尿病患者和101例正常对照者,采用聚合酶链式反应--限制性内切酶长度多态性(PCR-RFLP)技术,对脂联素基因SNP45多态性位点进行基因分型,同时测定代谢参数.结果 2型糖尿病组SNP45位点GG基因型频率和G等位基因频率均高于正常对照组(P＜0.05).结论 脂联素基因的SNP45多态性位点与宁夏汉族人群中2型糖尿病相关;GG基因型者具有2型糖尿病高易感性.     

PLA2G2A polymorphisms are associated with metabolic syndrome and type 2 diabetes mellitus. Results from the genetics of atherosclerotic disease Mexican study

The secretory phospholipase A₂ II A (sPLA₂-IIA) encoded by PLA2G2A gene hydrolyzes phospholipids liberating free fatty acids (FFAs) and lysophospholipids. If lipolysis exceeds lipogenesis, the free fatty acids undergo a continuous release into circulation. A sustained excessive increase in this release contributes to metabolic disease. The aim of the present study was to evaluate the role of PLA2G2A gene polymorphisms as susceptibility markers for metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM) in Mexican population. Three PLA2G2A gene polymorphisms (rs876018, rs3753827 and rs11573156) were genotyped by 5′ exonuclease TaqMan assays in a group of 338 patients with T2DM, 460 individuals with MetS and 366 healthy controls. Under codominant 1 (codom1), dominant (dom) and additive (add) models adjusted by age, gender, body mass index (BMI), smoking habit, and hypertension, the rs876018 T allele was associated with increased risk of MetS [Odds Ratio (OR) = 1.66, P_codom1 = 0.005; OR = 1.67, P_dom = 0.003; OR = 1.49, P_add = 0.005] as compared to controls. On the other hand, under several models adjusted by the same variables, the rs3753827 A (OR = 1.52, P_codom1 = 0.039 and OR = 1.49, P_dom = 0.039) and rs11573156C alleles (OR = 6.46, P_codom1 = 0.013; OR = 6.70, P_codom2 = 0.009; OR = 6.65, P_dom = 0.009) were associated with increased risk of T2DM when compared with controls. In addition, the rs876018 T allele was associated with hypercholesterolemia (P_dom = 0.017, P_add = 0.009) and risk of subclinical atherosclerosis (SA) (P_dom = 0.041) in MetS when compared with controls. Also, this allele was associated with SA in T2DM patients (P_dom = 0.007). The TAG haplotype was significantly associated with increased risk of MetS (OR = 1.54, P = 0.006). Results suggest that PLA2G2A polymorphisms are involved in the risk of developing MetS and T2D and are associated with SA in this group of patients.     

The association between rs1893217, rs478582 in PTPN2 and T1D risk with different diagnosed age,and related clinical characteristics in Chinese Han population

Objective: To investigate the association between polymorphisms in PTPN2 (rs1893217 and rs478582) and type 1 diabetes (T1D) risk with different diagnosed age, as well as related clinical characteristics in Chinese Han population.

Methods: A total of 2270 Chinese Han individuals (1023 T1D patients and 1247 healthy controls) were genotyped for rs1893217 and rs478582. And 306 newly diagnosed T1D patients were measured for C-peptide levels based on a standard mixed-meal tolerance test. In addition, 40 healthy controls were analyzed for different T cell subsets by multi-color flow cytometry.

Results: Neither rs1893217 nor rs478582 showed any association with T1D risk under an additive model. Stratified analysis for T1D diagnosed age revealed that rs1893217, but not rs478582, was significantly associated with T1D patients diagnosed age ≤18 (OR =0.80, 95% CI: 0.67–0.97, p?=?0.02). For those diagnosed age >18, neither of them showed any association. We also found that rs1893217 had a higher positive rate of ZnT8A (CC vs. TT carrier, OR = 2.07, 95% CI: 1.07–4.03, p?=?0.026) and IA-2A (CT vs. TT carrier, OR = 1.36, 95% CI: 1.02–1.80, p?=?0.038). Furthermore, for rs478582, compared with TT, healthy individuals carrying CC/CT carriers had significantly lower frequency and Helios expression of naive Treg subsets (p?=?0.049 and 0.048 respectively), but not secreting or activating Treg subsets. In addition, we did not find any association between these two polymorphisms and residual β-cell function in newly diagnosed T1D patients.

Conclusions: Our results suggest that rs1893217 may increase the risk of early-onset T1D and affect humoral immunity, while rs478582 may affect Treg subsets.