2型糖尿病与正常人群中β3肾上腺素能受体基因Trp 6 4Arg多态性表型特征

目的研究中国人群肾上腺素能受体基因Trp64Arg错义突变频率,并了解该突变对2型糖尿病临床特征的影响。方法应用PCR-RFLP技术检测了相互间无一级亲属关系的124例2型糖尿病患者及138例非糖尿病对照人群中 肾上腺素能受体基因Trp64Arg错义突变;同时检查体重指数、腰臀比例、血压,测定血脂及OGTT或馒头餐试验中0分钟及120分钟血糖及胰岛素。结果非糖尿病人群中Trp64Arg等位基因频率为0.17;突变频率在糖尿病与非糖尿病之间相比无显著性差异(P>0.05);突变与否间上述临床特征相比无显著性差异(P>0.05)。结论该突变至少在其杂合子型可能不是中国人散发2型糖尿病的主要决定因素;纯合子突变型可能导致2型糖尿病早发,有待今后积累资料深入研究。     

2型糖尿病与正常人群中β3肾上腺素能受体基因Trp64Arg多态？…

目的 研究中国人群β３肾上腺素能受体基因Ｔｒｐ６４Ａｒｇ错义突变频率,并了解该突变对２型糖尿病临床特征的影响。方法 应用ＰＣＲ－ＲＦＬＰ技术检测了相互间无一级亲属关系的１２４例２型糖尿病患者及１３８例非糖尿病对照试验中０分钟及１２０分钟血糖及胰岛素。结果 非糖尿病人群中Ｔｒｐ６４Ａｒｇ等位基因频率为０．１７,突变频率在糖尿病与非糖尿病裸上比无显著性差异（Ｐ〉０．０５）;突变与否这临床特征相比无显著     

中国北方汉族人群β3-肾上腺素能受体基因Trp64Arg多态性与原发性高血压的相关性研究

目的:探讨我国北方汉族人群β3-肾上腺素能受体基因单核苷酸多态性位点Trp64Arg与原发性高血压的相关性。方法:入选在北京安贞医院就诊的北方汉族原发性高血压患者855例(原发性高血压组,HT组),以及同期在安贞医院健康体检中心体检血压正常的受试者665例(正常血压对照组,NT组)。运用TaqMan等位基因分型技术,采用ABI7900基因检测平台对受试者ADRB3基因Trp64Arg位点进行检测,评估该多态性位点与我国北方汉族人群原发性高血压发病风险的关系。结果:HT组和NT组的ADRB3基因Trp64Arg位点基因型频率间,差异有统计学意义(P=0.017)。其中,ArgArg、ArgTrp及TrpTrp基因型在HT组和NT组的分布频率分别为1.29%/2.87%、30.25%/25.53%及68.46%/71.69%。多因素Logistic回归分析结果显示,除显性模型和等位基因模型外(显性模型:OR=1.233,95%CI=0.916～1.659,P=0.168;等位基因模型:OR=1.073,95%CI=0.828～1.390,P=0.595),各遗传模型均显示该多态性与原发性高血压发病密切相关(隐形模型:OR=0.343,95%CI=0.138～0.850,P=0.021;纯合子模型:OR=0.368,95%CI=0.147～0.921,P=0.033;加性模型:OR=0.374,95%CI=0.150～0.932,P=0.035;超显性模型:OR=1.412,95%CI=1.038～1.920,P=0.028)。根据性别进行的亚组分析中,仅在女性人群中发现该相关性(P=0.026)。根据超体质量/肥胖与否以及性别联合是否超体质量/肥胖进行的分层分析中,均未发现该相关性。结论:在本研究人群中,β3肾上腺素能受体基因Trp64Arg多态性可能与原发性高血压相关,Arg64Arg纯合子可能会降低高血压发病风险,杂合子Arg64Trp可能是高血压发病的危险因素。     

中国北方汉族人2型糖尿病合并冠心病与KIF6基因Trp719Arg多态性的相关性

目的探讨中国北方汉族人群KIF6基因Trp719Arg多态性基因型和等位基因频率分布特点,及与2型糖尿病(DM)合并冠心病(CHD)的关联性。方法采用病例对照研究设计,应用聚合酶链反应限制性片段长度多态性(PCR-RFLP)技术分析了对照组(152例)、DM组(97例)、DM+CHD组(76例)KIF6基因Trp719Arg多态性;比较组间基因型和等位基因频率分布差异,研究基因多态性对血糖、血脂水平的影响。结果中国北方汉族人群Trp719Arg多态性TT、TC、CC基因型频率分别为0.281、0.499与0.220。T、C等位基因频率分别为0.531与0.469。KIF6基因Trp719Arg多态性基因型和等位基因频率组间分布差异无统计学意义(均为P>0.05)。KIF6基因Trp719Arg多态性对血糖、血脂水平无显著影响。Logistic回归分析显示,高血压、年龄(≥60岁)、低HDL-C水平(<1.04 mmol/L)是DM+CHD的独立危险因素(OR分别为2.850、12.977和4.006,均为P<0.05),C等位基因与DM+CHD的发生无统计学相关性。结论 KIF6基因Trp719Arg多态性可能不是我国北方汉族人群DM+CHD的独立危险因素。     

β3肾上腺素能受体基因Trp64Arg变异与2型糖尿病的关联研究

目前的研究表明，2型糖尿病(T2DM)是一种多因子疾病，有多个基因或基因位点的变异与之关联，但不同地区和不同人种之间却存在着明显的差异。这就表明T2DM不仅具有强烈的遗传倾向，而且有明显的遗传异质性。研究发现，β3肾上腺素能受体(ADRβ3)对调节人体能量平衡发挥重要作用，ADRβ3缺陷可增加糖尿病(DM)和肥胖的易感性，     

β_2-肾上腺素能受体多态性与高血压

高血压是一复杂疾病,环境和基因因素决定其最终的表型。大量研究提示,高血压患者体内存在β_2-肾上腺素能受体(β_2-AR)调节的改变,这些变动可能与β_2-AR编码区单核苷酸改变有关,其中16、27位点基因的改变很常见。本文对β_2-AR多态性参与高血压发病的病理生理学机制进行探讨。     

β_1肾上腺素能受体Gly389Arg多态性与原发性高血压的关系

目的探讨汉族人群β1肾上腺素能受体Gly389Arg多态性与原发性高血压的关系。方法采用聚合酶链反应-限制性长度片段多态性技术分析原发性高血压患者和正常人群β1肾上腺素能受体Gly389Arg多态性。结果高血压组Arg/Arg,Arg/Gly,Gly/Gly基因型频率分别为59.06%、35.09%、5.85%,正常对照组分别为43.55%、45.97%、10.48%;两组间三种基因型频率分布有统计学差异(χ2=7.420,P<0.05);高血压组Arg等位基因频率为76.61%,Gly等位基因频率为23.39%,正常对照组分别为66.53%、33.47%,两组间等位基因频率分布存在统计学差异(χ2=7.299,P<0.05);高血压组Arg纯合子基因型频率和Arg等位基因频率均明显高于对照组。结论β1肾上腺素能受体Gly389Arg多态性可能与原发性高血压发病有关。     

海南汉族2型糖尿病患者胰岛素受体底物1基因Gly972Arg多态性的研究

目的 研究胰岛素受体底物1（IRS。1）基因Gly972Argr矢变与海南汉族2型糖尿病（T2DM）的关系。方法应用聚合酶链反应-限制性片段长度多态性技术对海南汉族60例T2DM患者和60例糖耐量正常人群进行IRS-1基因Gly972Arg突变位点基因型检测。结果T2DM组IRS-1基因Gly972Arg突变频率13．3％,对照组IRS-1基因Gly972Arg突变频率3．3％,两者比较有统计学差异（r=7．2,P〈0．01）。结论IRS—1基因Gly972Arg突变可能与海南汉族T2DM的发生有相关性。     

β1肾上腺素能受体基因多态性与心血管疾病

β1肾上腺素能受体是在心肌细胞分布的主要β肾上腺素能受体亚型,在调节心率和心肌收缩力方面起主导作用。随着β1肾上腺素能受体基因两个单核苷酸多态性(singlenuclid polymorphism,SNP)的发现,β1肾上腺素能受体基因可能成为某些心血管疾病病因研究的候选基因,并可能与     

胰岛素受体底物1基因Gly972Arg多态性与2型糖尿病不相关

目的：探讨中国汉族人群胰岛素受体底物1（IRS－1）基因Gly972Arg多态性与2型糖尿病的关系。方法：选取102例2型糖尿病患者及102例糖耐量正常的患者配偶进行对照研究，应用聚合酶链反应－－限制性片断长度多态性的方法进行胰岛素受体底物1基因Gly972Arg多态性位点基因型检测。结果：IRS－1基因Gly972Arg突变频率在病例组和对照组均为2％，明显低于白人。结论：在中国汉族人群中，IRS－1基因Gly972Arg突变不是2型糖尿病的主要致病因素。     

Phenotypic characterization of the Trp64Arg polymorphism in the beta3-adrenergic receptor gene in normal weight and obese subjects

Summary The beta₃-adrenergic receptor, located mainly in fat cells of visceral adipose tissue, is involved in the regulation of lipolysis and thermogenesis. Recently, a mutation in the corresponding gene resulting in the replacement of tryptophan by arginine in position 64 (Trp64Arg) has been demonstrated, which associated with obesity and metabolic complications of obesity. We have investigated whether this polymorphism is associated with changes in beta₃-adrenergic receptor function or clinical characteristics in 40 non-obese and 43 obese non-diabetic subjects who underwent elective abdominal surgery. The beta-adrenergic receptor gene polymorphism was examined by restriction-enzyme cleavage conformation. Beta₃-adrenergic receptor function was investigated by measuring lipolysis in isolated visceral white fat cells incubated with noradrenaline (natural ligand) or (CGP) 12177 (selective beta₃-agonist). No homozygotes for the mutation were found. The allelic frequency of Trp64Arg was similar in obese and non-obese subjects (9.4 and 12.5 %, respectively). In obese and non-obese subjects there was no change in body mass index, body fat distribution, fat cell size, fasting circulating levels of insulin, glucose or lipids, blood pressure or adipocyte lipolysis induced by noradrenaline or CGP 12177 when Trp64Arg heterozygotes were compared with Trp64 homozygotes. Our results suggest that the Trp64Arg mutation in its heterozygous form is not a major determinant of beta₃-adrenergic receptor function (when assessed by lipolysis in white adipose tissue) or of the pathophysiology of obesity. [Diabetologia (1996) 39: 857–860] Received: 21 February 1996 and in revised form: 22 March 1996     

大多功能蛋白酶2基因与1型糖尿病易感性及发病年龄的关系

目的研究大多功能蛋白酶（ＬＭＰ）２基因与１型糖尿病（１ＤＭ）及其发病年龄的关系。方法７１例１ＤＭ患者及８６名健康人参加,根据发病年龄将１ＤＭ患者分为３组（≤１４岁组,１５～３０岁组,≥３１岁组）;采用聚合酶链反应限制性片段长度多态性（ＰＣＲＲＦＬＰ）技术进行ＬＭＰ２基因分型。结果ＬＭＰ２Ｒ／Ｒ、ＬＭＰ２Ｒ／Ｈ、ＬＭＰ２Ｈ／Ｈ、ＬＭＰ２Ｒ及ＬＭＰ２Ｈ频率在１ＤＭ组分别为４０．９％、５３．５％、５．６％、６７．６％、３２．４％,在正常对照组分别为５７．０％、３２．６％、１０．４％、７３．３％、２６．７％。ＬＭＰ２Ｒ／Ｈ频率在１ＤＭ组显著高于对照组（Ｐ＜０．０１）,而ＬＭＰ２Ｒ／Ｒ频率则显著低于对照组（Ｐ＜０．０５）;ＬＭＰ２各基因型及等位基因频率在１ＤＭ各发病年龄组之间无显著性差异（Ｐ＞０．０５）。结论ＬＭＰ２Ｒ／Ｈ可能为１ＤＭ的易感基因型,ＬＭＰ２Ｒ／Ｈ阳性者患１ＤＭ的危险性增加;ＬＭＰ２Ｒ／Ｒ可能是１ＤＭ的保护基因型,ＬＭＰ２Ｒ／Ｒ阳性者患１ＤＭ的危险性降低;ＬＭＰ２各个基因型及等位基因与１ＤＭ的发病年龄无     

Association of amino acid variation (Trp64Arg) in the beta3-adrenergic receptor gene with bone mineral density

Background:   Recent studies have revealed that a mis-sense mutation replacing tryptophan with arginine at codon 64 (Trp64Arg) of the beta3-adrenergic receptor ( β3-AR ) gene was associated with insulin resistance in non-diabetic subjects and to earlier onset of non-insulin dependent diabetes mellitus. To analyze a possible involvement of β3-AR in bone metabolism, we investigated the association between bone mineral density (BMD) and the Trp64Arg polymorphism.
Methods:  A large cohort of Japanese postmenopausal women comprised the study population. The genotypic frequencies in this cohort were Trp/Trp, 61.8%; Trp/Arg, 33.2%; and Arg/Arg, 5.0%.
Results:  When the subjects were separated into two groups, one bearing at least one Trp allele at codon 64 (Trp/Trp and Trp/Arg) and the other with none (Arg/Arg), the former subjects had significantly higher Z scores for total-body BMD (mean ± SD, 0.432 ± 0.93 versus −0.135 ± 0.93; P  = 0.033).
Conclusions:   These data suggested an association between this single-nucleotide polymorphism (SNP) in the β3-AR gene and BMD, and therefore a possible involvement of the Arg allele (or the absence of Trp64) in postmenopausal osteoporosis among Japanese women.     

瘦素受体基因变异与2型糖尿病各临床变量的关系

目的 研究瘦素受体基因（leptin receptor,Lepr)第20外显子基因变异与2型糖尿病患者各临床变量（如体重指数、腰围、臀围、收缩压、舒张压、空腹血糖、甘油三酯、总胆固醇等）的关系。方法 用聚合酶链反应－限制性酶切片段长度多态性（PCR－RFLP）测定90例2型糖尿病患者Lper第20外显子基因变异频率，常规检测血糖、甘油三酯、总胆固醇和高密度脂蛋白，于相同条件下测身高、体重，腰围和臀围，按公式计算体重指数（BMI）、脂肪百分比（％Fat)和胰岛素敏感指数（ISI）。结果 中国湖北地区糖尿病患者中存在Lepr第20外显子基因变异，其中2927位C→A（Ala976Asp)变异频率为100％，3057位G→A（Pro1019Pro)总的变异频率为80％；其3057位G→A变异与肥胖型2型糖尿病患者的胰岛素敏感指数呈负相关（P＜0.001)，与女性糖尿病患者的腰围／臀围呈正相关（P＜0.05)；Logistic回归分析发现，Lepr基因3057位G→A变异与体重指数（BMI）、腰围／臀围、舒张压、甘油三酯呈正相关，与高密度脂蛋白及ISI呈负相关。结论 中国人糖尿病患者中存在Lepr第20外显子基因变异，其变异主要影响2型糖尿病患者脂质代谢、局部体脂分布并参与胰岛素抵抗的发生。     

β3-肾上腺素受体基因多态性与代谢综合征关系的前瞻性研究

目的 探讨β3-肾上腺素受体(β3-AR)基因变异与代谢综合征(MS)发生的关联.方法 2000年筛查出的单纯肥胖者(BMI≥25 kg/m2)386例以及正常体重健康人175例,根据基线时测定的β3-AR基因型分为肥胖Trp64纯合子组(OB1组)和Arg64携带者组(OB2组)及正常体重Trp64纯合子组(NW1组)和Arg64携带者组(NW2组),7年后对此人群进行随访.结果 基线资料显示,体脂、血压、血脂、血糖、空腹胰岛素在OB1组与OB2组之间和NW1组与NW2组之间比较差异无统计学意义.随访发现,OB2组男性MS发生率明显高于OB1组男性(54.76%比40.85%,P<0.05),同一比较在OB2组与OB1组女性中未显示出统计学差异.OB1组和OB2组中男性MS发生率均显著高于本组女性(40.85%比18.27%和54.76%比21.28%,P值均<0.01),NW1组与NW2组发生MS者无论在男性或女性中比较以及同组男女之间比较差异均无统计学意义.总体比较,无论有无β3-AR基因变异,肥胖者MS的发生率均显著高于正常体重者(31.30%比6.03%和42.75%比12.73%,P值均<0.01).Logistic分析进一步显示,β3-AR基因变异与男性MS相关.结论 β3-AR基因变异是男性MS的独立危险因素.     

β3-肾上腺素能受体基因多态性与超重和肥胖人群血管内皮功能障碍的相关研究

目的 研究β3-肾上腺素能受体（β3-AR）基因多态性对超重和肥胖人群血管内皮功能的影响以及与某些代谢指标的关系。方法 超重组234例。肥胖组152例和正常体重组175例。测定β3-AR基因Trp64Arg的基因频率，并通过高分辨率超声评价血管内皮功能。同时。测定体重指数，腰围，腰臀比，血压，知脂，空腹血糖和胰岛素，餐后血糖和胰岛素及IR指数（HOMA-IR）。结果 （1）超重，肥胖和正常体重组之间Arg64等位基因频率差异无显著性；超重组和肥胖组内皮依赖性舒张功能较无突变者显著降低。（2）无论有无基因突变。超重或肥胖组血压，甘油三酯，空腹血糖和胰岛素，餐后血糖和胰岛素及HOMA-IR等代谢指标均高于正常体重组，各组突变与无突变者之间差异无显著性。（3）血管内皮功能在无突变者与体重指数，腰围腰臀比甘油三酯，空腹血糖和胰岛素，餐后胰岛素及HOMA-IR显著负相关。在突变者与体重指数，腰围，腰臀比。空腹胰岛素和HOMA-IR显著负相关。结论 β3-AR基因多态性与超重和肥胖人群血管内皮功能障碍有关。而IR及某些代谢指标也是内皮功能障碍发生的重要因素。     

The Trp64Arg polymorphism of the beta3-adrenergic receptor gene is associated with hypertension in men with type 2 diabetes mellitus

A missense mutation of the beta3-adrenergic receptor gene (ADRB3) resulting in a tryptophan/arginine exchange at position 64 (Trp64Arg polymorphism) has recently been associated with greater capacity to gain weight, a low resting metabolic rate, higher blood pressure, and an early onset of type 2 diabetes. These findings prompted us to examine the relationship between this mutation, blood pressure, and vascular complications in German patients with type 2 diabetes. White patients with type 2 diabetes mellitus (n = 417) were enrolled in the study. The Trp64Arg polymorphism of the ADRB3 gene was detected by polymerase chain amplification and subsequent restriction digest with BstN I. Stepwise logistic regression analysis of the entire study population revealed a significant interaction between gender and genotype (P = .019). We therefore performed separate analyses for men and women. There was a significant relationship between hypertension and the ADRB3 Trp64Arg variant in men (P = .015), but not in women. Furthermore, blood pressure levels in male patients with the minor allele had higher blood pressure levels (P < .05), despite a significantly greater number of antihypertensive medications (P = .01). There was no association between ADRB3 genotype and vascular complications in these patients. In conclusion, our data are compatible with a contribution of this genetic variant of ADRB3 to hypertension in male patients with type 2 diabetes. Further studies will be needed to determine the role of this polymorphism as a predictor of hypertension or vascular complications in patients with type 2 diabetes.