瘦素受体Gln223Arg基因多态性与肥胖关系的研究

目的 研究瘦素受体Gln223Arg基因多态性与肥胖的关系。方法 2004年在山西省盂县选取一组人群，凋查其心血管病危险因素，同时抽血检测瘦素受体Gln223Arg基因多态性的基因型，并分析Gln223Arg基因多态性与肥胖的关系。结果 该组人群GG、GA及AA的基因型频率分别为0．7679、0．2171和0．0151；G和A等位基因频率分别为0．8764和0．1236。基因型频率分布符合Hardy-Weinberg平衡（P=0．934）。单因素分析结果表明携带A等位基因的研究对象具有更高的体重（63．2kg vs．61．9kg；P=0．0307）和体重指数（24．4kg／m^2 vs．24．1kg／m^2；P=00898）；在调整年龄、性别、体力活动和膳食之后，携带A等位基因者仍然具有较高的体重指数（24．5kg／m^2 vs．24．1kg/m^2；P=0．0396）和肥胖患病率（OR=1．30，95％CI：0．957～1．767；P=0．0935）。结论 瘦素受体Gln223Arg基因多态性与肥胖可能有关。     

武汉地区高血压合并肥胖与瘦素受体基因GIN 223Arg变异的关系

目的研究武汉地区高血压合并肥胖与瘦素受体基因GIN223Arg变异的关系。方法运用聚合酶链反应-限制性片段长度多态性(PCR-RELP)方法测定具有完整临床资料的644例武汉地区居民的瘦素受体基因Gln223Arg变异的基因型,其中包括高血压合并肥胖256例,高血压非肥胖136例及对照者252例。结果瘦素受体基因Gln223Arg变异与男性高血压合并肥胖相关,A等位基因与男性患者的体质指数、收缩压及舒张压相关,P值分别为0.031,0.023,0.036。Logistic回归分析显示,携带A等位基因的男性高血压合并肥胖患者比值比(OR)为2.513(95%可信限为1.216～5.129)。结论瘦素受体基因Gln223Arg变异与男性高血压合并肥胖者体质指数、收缩压和舒张压均相关,是男性高血压合并肥胖的独立危险因素。     

LEPR基因Gln223Arg多态性与上海某区汉族儿童的相关性研究

目的探究瘦素受体基因Gln223Arg多态性与上海某区儿童超重肥胖的关系及相关生化指标的相关性。方法采用PCR-RFLP对上海松江区六所小学7-11岁超重肥胖与正常体重儿童(各262名)的血样进行LEPR基因Gln223Arg多态性检测,logistic回归分析其与儿童超重肥胖的相关性,并分析了生化指标在超重肥胖组与正常组儿童以及不同基因型间的差异。结果超重肥胖组与对照组之间LEPR基因Gln223Arg AA频率与A等位基因频率均无统计学差异(P>0.05)。对其收缩压(SBP),舒张压(DBP),胆固醇(TC),甘油三酯(TG),血糖(GLU),高密度脂蛋白胆固醇(HDL-C),低密度脂蛋白胆固醇(LDL-C)进行t检验,得出SBP,DBP,TG,HDL-C和LDL-C在超重肥胖组与对照组中差异显著。在控制了混杂因素BMI等后,LEPR基因Gln223Arg各基因型组的生化指标差异分析表明基因型可能与LDL-C相关(P<0.05)。进一步两两比较结果表明LDL-C水平在基因型AA组比AG(P=0.019)与GG组(P=0.017)低,而AG与GG组之间的差异无统计学意义(P=0.517)。结论 LEPR基因Gln223Arg多态性可能与儿童超重肥胖的发生无关,而LDL-C(P<0.05)可能与LEPR基因Gln223Arg基因型有相关性。     

瘦素及瘦素受体基因多态性与乳腺癌的相关性研究

目的探讨瘦素及其瘦素受体基因多态性与乳腺癌发生的关系。方法采用PCR- RFLP对94例乳腺癌患者、128例健康对照者进行瘦素受体基因Gln223Arg多态性检测;ELISA分析法测定瘦素水平。结果乳腺癌组瘦素受体基因Gln223Arg的GG、GA和AA基因型表达频率分别为69.15%、17.02%和13.83%;等位基因G和A为77.66%和22.34%与对照组82.03%、15.63%和2.34%及等位基因的89.84%和10.16%相比较,差异有统计学意义(P=0.004,P=0.001)。乳腺癌组瘦素水平,腰臀比(WHR)明显高于对照组,差异均有统计学意义(P<0.01,P<0.001)。非条件logislic回归多因素分析表明,瘦素受体基因多态性、瘦素水平及WHR升高,与乳腺癌发生的相关危险度分别为:OR=4.87,95%CI:1.30-18.22,P=0.019;OR=1.53,95%CI:1.13-2.07,P= 0.006;OR=3.68,95%CI:1.34-10.11,P=0.011。结论瘦素受体基因Gln223Arg多态性、瘦素及WHR升高,可能增加乳腺癌发生的风险性。     

瘦素受体基因Gln223Arg多态性与肥胖的关联研究

目的探讨瘦素受体基因多态性与肥胖发生的关系。方法采用PCR-RFLP对502例肥胖患者、400例体重正常者进行瘦素受体基因Gln223Arg多态性检测。结果肥胖组瘦素受体基因Gln223Arg的GG、GA和AA基因型表达频率分别为0.777、0.197及0.026。单因素分析显示携带AA基因型与携带GG基因型相比,发生肥胖的风险为OR=0.478,P=0.043。多因素分析表明,瘦素受体基因多态性、年龄>65岁、吸烟以及口味偏重与肥胖发生的相对危险度分别为:OR=1.36,95%CI:0.999~1.849,P=0.05;OR=0.55,95%CI:0.366~0.825,P=0.004;OR=1.475,95%CI:1.064~2.045,P=0.02;OR=1.506,95%CI:1.042~2.176,P=0.029。结论瘦素受体基因Gln223Arg多态性可能与肥胖发生有关。     

XRCC1399与XPD751基因多态性与苯乙烯致周围血淋巴细胞损伤关系

目的探讨DNA修复基因X线修复交叉互补基因1(XRCC1)399与人类着色性干皮病基因D(XPD)751基因多态性与苯乙烯致周围血淋巴细胞损伤的关系。方法 选取山东省某机车外壳生产厂126名苯乙烯作业人员为接触组,150名非苯乙烯作业人员为对照组。应用限制性片段长度多态性聚合酶链反应技术检测患者XRCC1 399位点和XPD 751位点的基因多态性,分析其与苯乙烯致周围血淋巴细胞损伤的关系。结果 XRCC1 399 Arg/Gln分布主要以Gln/Gln和Arg/Gln基因型为主,Arg/Arg基因型仅出现在少数人群中。XPD 751 Lys/Gln主要以Lys/Lys基因型为主,未发现Gln/Gln基因型者,2种基因的基因型均符合Hardy-Weinberg平衡。接触组携带XRCC1 399 Arg/Gln和Gln/Gln基因型的个体周围血淋巴细胞双核微核率低于Arg/Arg基因型者,差异有统计学意义(P<0.05),携带XPD 751 Lys/Gln基因型的个体周围血淋巴细胞双核微核率高于Lys/Lys基因型者,差异有统计学意义(P<0.05)。结论 XRCC1 399和XPD751基因多态性可能与苯乙烯致周围血淋巴细胞损伤有关系。     

DNA修复基因XRCC1多态性及EB病毒感染与鼻咽癌易感性的关联

目的 研究X射线交错互补修复基因1(XRCC1)多态性及EB病毒(EBV)感染与鼻咽癌(NPC)易感性的关系,为临床筛查、预防和诊治提供参考依据。方法 选取2018年4月-2021年4月济南市人民医院97例初治NPC患者和92名健康体检人群分别为NPC组和对照组,比较两组EBV-DNA水平,分析XRCC1基因Arg194 Arg/Trp、Arg280 Arg/His和Arg399 Arg/Gln多态性。结果 NPC组吸烟史、家族史和EBV-DNA阳性占比均高于对照组(P<0.05); NPC组和对照组XRCC1基因Arg194 Arg/Trp、Arg280 Arg/His和Arg399 Arg/Gln位点基因型分布均满足Hardy-Weinber平衡定律(P>0.05),且NPC组Arg194 Trp/Trp基因型和Trp等位基因分布频率分别为(6.19%和31.44%)低于对照组,Arg399 Gln/Gln基因型和Gln等位基因分布频率分别为(28.87%和52.58%)高于对照组,比较差异均有统计学意义(P<0.05)。结论 XRCC1基因多态性和EBV感染可能导致NPC发病风险升高。     

汉族人群XRCC1基因多态性与神经胶质瘤易感性的相关性研究

目的探讨X线交错互补修复基因1(XRCC1)基因多态性与神经胶质瘤易感性的相关性。方法对368名汉族脑胶质瘤患者和346名健康对照者进行基因分型,XRCC1 Arg194Trp(rs1799782)、Arg280His(rs25489)、Arg399Gln(rs25487)三种多态性进行直接测序。结果胶质瘤组Arg280His A等位基因频率显著低于健康对照组中频率(9.65%vs 16.04%,OR=0.60(0.46~0.80),P0.001);GA与AA基因型频率两组间差异有统计学意义(16.58%vs 22.83%;1.36%vs 4.63%)。Arg399Gln A等位基因频率胶质瘤组显著高于健康对照组(38.72%vs 30.06%,OR=1.29(1.11~1.49),P=0.001);GA或AA基因型的频率两组差异有统计学意义(45.38%vs 38.15%;16.03%vs 10.98%)。rs1799782(Arg194Trp)等位基因或基因型频率未发现不同。结论中国汉族人群XRCC1基因Arg280His(rs25489)和Arg399Gln(rs25487)多态性可能会影响胶质瘤的易感性。     

中国人群瘦素受体Gln223Arg、Pr01019Pro基因多态性与肥胖关联性的Meta分析

目的 探讨瘦素受体(LEPR)Gln223Arg、Prol019Pro基因多态性与肥胖的关联性。方法 计算机检索万方、CNKI、维普、CBM、PubMed、EMBASE数据库,收集1979-2010年公开发表的关于中国人群LEPR Gln223Arg、LEPR Pro1 019Pro基因多态性与肥胖的病例对照研究的文献,选择OR值及其95%CI作为Meta分析指标。利用Stata 10.0软件对各研究结果进行异质性检验和效应值合并计算。结果 根据统一的纳入和剔除标准,纳入15篇文献,其中LEPR Gln223Arg基因多态性相关文献9篇,共有肥胖者1096例,对照组949人;LEPR Prol019Pro基因 多态性相关文献8篇,共有肥胖者961例,对照组818人。LEPR Gln223Arg基因多态性与肥胖关联性的研究中,LEPR-668位点基因G/A的OR=0.66（95%CI:0.49～0.89),将有A→3基因突变的AG基因型和GG基因型合并后与AA基因型比较,肥胖易感性降(OR=0.50,95%CI: 0.32～ 0.77)有统计学意义;在LEPR Prol019Pro基因多态性与肥胖关联性的研究中,LEPR-3057位点基 因A/G的OR= 1,61 (95%CI: 1.15～2.26),有G→A基因突变的基因型AG和基因型AA合并后与GG基因型比较,肥胖易感性升高（OR= 1.50,95%CI: 1.08～2.08),有统计学意义。结论 中国汉族为主的人群LEPR Gln223Arg和LEPR Prol019Pro基因多态性与肥胖的发生均有关联。     

青春前期女童钙感应受体基因多态性与骨量关系

目的了解我国青春前期女童钙感应受体（CASR）A986S基因多态性分布并探讨其对骨量的影响。方法选择153名9～11．5岁未月经初潮的健康女童，采用双能X线骨密度仪（DXEA）检测对象全身、L1—L4腰椎、左侧近端股骨的骨矿含量、骨密度以及体成分。采用等位基因特异性突变扩增PCR技术检测CASRA986S多态性。结果152名对象CASR基因A986S多态性基因型的分布频率分别为：野生型纯合子（AA）91．44％，杂合子（AS）7，89％，突变型纯合子（SS）为0．67％，研究对象基因型中含有s等位基因者TBBMD、TBBMC，L1-L4LSBMD均显著低于基因型中不含S等位基因者（P〈0．05）。其中含S等位基因者TBBMD比无S等位基因者低5％，TBBMC下降了约10％。结论CASRA986S基因多态性与骨量有关。有S等位基因者TBBMC、TBBMD显著低于无S基因者。     

LEPR G1n223Arg多态性对不同种族人群中乳腺癌危险性影响的meta分析

瘦素和瘦素受体参与了乳腺癌的发生发展过程。在瘦素受体基因（LEPR）6号外显子上第223个密码子A到G的转变可以导致谷氨酸到精氨酸的替换（Gln223Arg）。许多已发表的病例对照研究评价了LEPRGln223Arg多态性与乳腺癌的关系。然而,却未得出一致的结论。本篇meta分析囊括了8篇文献来评价LEPRGln223Arg多态性与乳腺癌的联系。用总体合并OR值作为研究共显性模型、隐性模型、显性模型的指标。结果显示总体研究中隐性模型（OR=1．32,95％CI：1．03～1．69）和Arg/Gln vs Gin／Gin基因型（OR=1．16,95％CI：1．01～1．34）显著提高了乳腺癌的危险性。种族分层分析中发现,非洲人群的以下几个基因型会提高患乳腺癌的危险性：Arg/Arg vs 8Gln/Gln（OR=1．86,95％CI：1．28-2．71）,Arg／Gln vs GIn/Gln（OR=1．48,95％CI：1．10—1．99）,显性模型（OR=1．60,95％CI：1．21～2．11）和隐性模型（OR=1．48,95％cI：1．07～2．05）;亚洲人群中,Arg／ArgvsGin／Gin基因型（OR=6．79,95％CI：3．42～13．47）和显性模型（OR=2．03,95％CI：1．42～2．90）提高了患乳腺癌的危险性。在欧洲人群中任何基因模型都没有发现能显著提高乳腺癌的危险性。总而言之,LEPR223Arg是乳腺癌发展的低风险因素,特别是在非洲女性中。     

Genetic variation in the leptin receptor gene,leptin, and weight gain in young Dutch adults

OBJECTIVE: To investigate the association between leptin levels, polymorphisms in the leptin receptor (LEPR) gene, and weight gain. RESEARCH METHODS AND PROCEDURES: From two large prospective cohorts in The Netherlands (n = 17,500), we compared the baseline leptin of 259 subjects who had gained an average of 12.6 kg (range 5.5 to 33 kg) with 277 subjects who kept stable weight (range -2.6 to 3.1 kg) after a mean follow-up of 6.8 years. Three polymorphisms in the LEPR gene (Lys109Arg, Gln223Arg, and Lys656Asn) were determined. RESULTS: Weight gainers had significantly higher baseline leptin levels than those who kept stable weight (odds ratio = 1.27, 95% confidence interval 1.1 to 1.5, per SD increase in log(e)-transformed leptin). Weight gainers with the Arg109 or the Arg223 alleles had higher leptin levels compared with the noncarriers of these alleles. Only among men, the association between leptin and weight gain tended to be stronger among those with an Arg223 allele compared with those without this mutation. DISCUSSION: Relatively high leptin levels predict weight gain, suggesting that leptin resistance plays a role in the development of obesity in the general population. Higher leptin levels for those with a Lys109Arg or Gln223Arg mutation (or a linked other marker) may imply that these subjects have a modified functional leptin receptor. However, the role of these mutations on weight gain is limited.     

Leptin levels,leptin receptor gene polymorphisms,and energy metabolism in women

OBJECTIVE: Resting metabolic rate (RMR) is mainly determined by fat-free mass and additionally by age, sex, hormones, and possibly genetic differences. We evaluated whether leptin levels and polymorphisms in the leptin receptor (LEPR) gene were associated with energy expenditure phenotypes. METHODS: RMR, body composition, and leptin levels were measured in 125 overweight and obese women. Three LEPR polymorphisms, Lys109Arg, Gln223Arg, and Lys656Asn, were typed on genomic DNA of another group of 192 women in whom RMR was measured. Fat, protein, and carbohydrate oxidation were calculated for 103 of these subjects. In 38 subjects, glucose-induced thermogenesis was measured over 3 hours. RESULTS: In the first study group, a negative correlation between RMR and leptin levels was found after controlling for fat and fat-free mass. In multiple regression analysis, leptin contributed significantly to RMR, independent of body composition. In the second study group, RMR was not associated with LEPR polymorphisms. Differences in substrate oxidation rates were found among genotypes at the Lys656Asn site. In fasting conditions, Lys656Lys showed a trend to oxidize more carbohydrates and less fat than Asn656 carriers, a trend which became significant after the glucose load when carbohydrate oxidation rate in Lys656Lys was 15% higher than in Asn656 carriers (p = 0.04), and fat oxidation rate was 44% lower (p = 0.02). DISCUSSION: These results suggest that DNA sequence variations in the LEPR gene could affect substrate oxidation. We hypothesize that this might be caused by differences in glucose levels, leading to differences in glucose oxidation rates.     

Leptin responsiveness to energy restriction: genetic variation in the leptin receptor gene

Serum leptin concentrations are an important afferent signal in energy balance homeostasis. It has been speculated that the leptin responsiveness to energy restriction is affected by the functionality of the leptin receptor. The purpose of this analysis was to explore the effect of polymorphisms in the LEPR gene on the acute decline in leptin after 4 days of 65% energy restriction. Leptin concentrations of the study group (n = 44; all men) declined by 2.3 +/- 1.5 micro g/L [-39.4% (95% confidence interval: -43.6 to -34.9)]. Leptin responses did not statistically differ between noncarriers and carriers of three mutant variants of the polymorphisms: Lys109/Lys109 (-41.4%) vs. Arg109/+ (-37.0%) (p = 0.33); Gln223/Gln223 (-41.5%) vs. Arg223/+ (-37.8%) (p = 0.40); Lys656/Lys656 (-39.5%) vs. Asn656/+ (-39.3%) (p = 0.96). No effect of the assessed polymorphisms in the LEPR gene on the acute decline in leptin after energy restriction was observed. Power calculations are provided for future studies on the leptin responsiveness to energy restriction.     

维生素D受体基因起始密码子多态性与体力活动对青春期女童骨量增长的交互作用

目的 探讨维生素D受体(VDR)基因起始密码子(Fok I位点)多态性与体力活动对青春期女童骨量增长的交互作用.方法 选择228名9～11.5岁未月经初潮的健康女童进行2年追踪,应用双能X线骨密度仪检测对象追踪前后全身、左侧近端股骨(包括股骨颈、大转子、粗隆间和华氏三角区)和L1～L4腰椎骨密度,应用PCR-RFLP技术检测VDR基因Fok I位点多态性.结果 本次研究的有效观察人数为176名.Fok I位点多态性与骨密度(BMD)2年增长率没有关联.在低体力活动水平(<1197 kJ/d)时,FF基因型女童左侧近端股骨骨密度(THBMD)和股骨颈骨密度(FNBMD)增长率低于Ff+ff基因型女童,差异有统计学意义;体力活动与THBMD和FNBMD增长率有关联,但仅限于FF基因型女童.结论 VDR基因Fok I多态性与体力活动水平对青春期女童骨量增长存在交互作用,低体力活动水平的FF基因型女童可能是骨量增长较低的危险人群,体力活动能促进FF基因型女童骨量增长.     

Leptin, soluble leptin receptor, lipid profiles, and LEPR gene polymorphisms in Thai children and adolescents

OBJECTIVE: To evaluate the relationships between leptin, soluble leptin receptor, lipid profiles, and LEPR gene polymorphisms in child and adolescent Thai subjects. DESIGN: Cross-sectional study of Thai children and adolescents. SUBJECTS: 116 male and 65 female at risk for overweight/overweight child and adolescent Thai subjects, and 33 male and 62 female healthy child and adolescent Thai subjects (age: 5-19 years). MEASUREMENTS: Leptin levels, soluble leptin receptor levels, lipid profiles, LEPR gene polymorphisms. RESULTS: Significantly higher levels of cholesterol, triglyceride, low-density lipoprotein cholesterol (LDL-C), and leptin levels were observed in at risk for overweight/overweight group. On the other hand, high-density lipoprotein cholesterol (HDL-C) and soluble leptin receptor levels were significantly lower in the same group. Serum soluble leptin receptor levels were significantly negatively correlated with leptin. The at risk for overweight/overweight subjects with the Lys656Lys homozygous wild type LEPR gene had significantly higher cholesterol and LDL-C levels than those with Lys656Asn heterozygous and Asn656Asn homozygous mutant type. In contrast, subjects with Lys656Lys homozygous wild type had significantly lower leptin levels than those with Lys656Asn heterozygous and Asn656Asn homozygous mutant type. There was a statistically significant association between body mass index (BMI) and hyperleptinemia (odds ratio; OR = 2.49, p = 0.000) and females had more increased risk of hyperleptinemia than males (OR = 15.74, p = 0.004) in adolescent Thai subjects. CONCLUSION: The present study is the first report of Lys656Asn polymorphism of the LEPR gene associated with cholesterol, LDL-C, and leptin levels in Thai children and adolescents. Serum leptin levels were significantly higher in the at risk for overweight/overweight. In contrast, there were significantly lower soluble leptin receptor levels in the same group. In addition, there was a statistically significant association between BMI, sex, and hyperleptinemia in adolescent Thai subjects.