瘦素受体基因Gln223Arg多态性与代谢综合征的相关性及其对心脏结构功能的影响

目的:探究瘦素受体基因Gln223Arg多态性与代谢综合征的相关性及其对心脏结构功能的影响。方法:研究对象为2005-10至2008-06我院门诊初诊未治疗的167例代谢综合征患者(代谢综合征组)和216例健康体检者(对照组)。测量血压、生化指标、胰岛素及超声心动图等,限制性片段长度多态性聚合酶链(PCR-RFLP)法分析Gln223Arg基因多态性和测序验证基因型。结果:代谢综合征组携带A等位基因频率明显高于对照组,携带A等位基因者发生代谢综合征的几率是携带G等位基因的3.302倍[P=0.000;95%可信区间(CI):2.432~4.483]。初诊而未治疗的代谢综合征患者已出现左心室肥厚重构和舒张功能减低。代谢综合征组携带A等位基因的患者较携带G等位基因者有更高的体重指数、血压、血糖和空腹胰岛素水平,更大的腰围,更严重的血脂紊乱、胰岛素抵抗、左心室肥厚及舒张功能减低。结论:瘦素受体基因Gln223Arg多态性A等位基因携带者发生代谢综合征的风险较大,更倾向于发生左心室肥厚。     

糖耐量损伤者瘦素受体基因Gln223Arg多态性研究

目的 探讨糖耐量受损者瘦素受体基因Gln223Arg多态性与血清瘦素水平及胰岛素抵抗的相关性.方法 从2007年1月至2009年8月在宁波市第二医院检验科进行糖耐量试验的门诊患者中筛选未接受任何抗糖尿病治疗且血常规及肝肾功能正常者.649名合格者据其糖耐量试验结果分为正常糖耐量组(n=298,男168名,女130名,平均年龄42岁)及糖耐量受损组(n=351,男188例,女163例,平均年龄46岁).检测甘油三酯、总胆固醇、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、糖化血红蛋白、空腹血糖、胰岛素、瘦素、胰岛素抵抗及瘦素受体基因Gln223Arg多态性.采用t检验及χ~2检验分析瘦素受体基因Gln223Arg多态性与血清瘦素及胰岛素抵抗的相关性.结果 糖耐量受损组Gln223Gln基因型比例高于正常糖耐量组(χ~2=7.38,P<0.05),体重指数、甘油三酯、总胆固醇、低密度脂蛋白胆同醇、空腹血糖、糖化血红蛋白、胰岛素、胰岛素抵抗及瘦素水平显著高于正常糖耐量组(t值分别为13.168、10.816、6.704、16.459、26.553、9.521、17.108、28.122、5.829、6.602,均P<0.01).223Arg等位基因缺失的糖耐量受损患者总胆同醇、低密度脂蛋白胆固醇、胰岛素、胰岛素抵抗、瘦素高于携带该等位基因的糖耐量受损患者(t值分别为2.294、3.744、3.892、7.633、2.263、2.479,均P<0.05),但两者甘油三酯、高密度脂蛋白胆固醇、糖化血红蛋白及空腹血糖水平无显著差异(t值分别为0.343、-0.494、-1.175、1.404,均P>0.05).223Arg等位基因缺失(Gln223Gln)与男性糖耐量受损相关[比值比(OR)=2.32,P<0.01] ,与女性糖耐量受损无显著相关(OR=1.45,P>0.05).结论 瘦素受体基因Gln223Arg多态性与血脂、血清瘦素水平及男性糖耐量受损的发生、发展密切相关.     

瘦素受体基因Gln 223Arg变异与武汉地区肥胖合并高血压患者相关性研究

目的 研究瘦素受体基因Gln 223Arg变异与肥胖合并高血压的关系.方法 运用聚合酶链反应-限制性片段长度多态性(PCR-RELP)方法 测定无亲缘关系,且有完整临床资料的766例武汉地区汉人的瘦素受体基因Gln 223Arg变异的基因型(包括252例正常对照者及肥胖合并高血压256例,非肥胖高血压患者136例,单纯肥胖者122例).结果 肥胖合并高血压不同性别,不同瘦素受体基因Gln 223Arg变异的高血压合并频率比较发现,瘦素受体基因Gln 223Arg变异与男性肥胖合并高血压相关,A等位基因与男性较高的收缩压(P=0.023)及舒张压(P=0.036)及BMI(P=0.031)相关.Logistic回归分析证实,该基因变异是肥胖男性合并高血压的独立风险因子(P=0.036).携带"A"等位基因的男性肥胖合并高血压发生的比数比(OR)为2.711(95%可信限为1.216、5.129).结论 瘦素受体基因Gln 223Arg变异与肥胖男性合并高血压相关,收缩压和舒张压及BMI均相关.     

瘦素受体基因多态性与云南地区人口高血压及代谢特征的相关性研究

目的:探讨瘦素受体(Lepr)基因多态性与云南地区汉族人高血压及其临床代谢特征的相关性。方法:选取云南地区汉族高血压病住院患者200例,以体重指数分为超重高血压组141例和单纯高血压组59例两个亚组,同期选取正常对照组100例。采用聚合酶连反应-限制性片段长度多态性(PCR-RELP)方法测定Lepr基因Gln223Arg和Lys109Arg多态性,ELISA法测定血中瘦素水平。结果:Gln223Arg位点A等位基因的频率在超重高血压明显高于单纯高血压组,并且有着更高的BMI(P<0.01)。超重高血压患者中携带Lys109Arg基因型A等位基因者低密度脂蛋白胆固醇(LDL-C)高于G等位基因者(P<0.01)。结论:Gln223Arg多态性与肥胖密切相关,Lys109Arg多态性与超重高血压患者脂代谢紊乱相关。     

瘦素水平及其受体基因多态性与原发性肝癌的相关性研究

目的 探讨瘦素及其受体基因多态性与原发性肝癌的相关性.方法 收集82例原发性肝细胞癌病人和102例健康体检者的外周血,采用PCR-RFLP方法检测瘦素受体基因Gln223Arg的多态性,同时运用ELISA法检测血清瘦素水平.结果 肝癌组和正常对照组瘦素受体基因Gln223Arg多态性基因型和等位基因的频率分布具有显著性差异(P<0.01);肝癌组的血清瘦素水平明显高于正常对照组[(3.42±1.25)ng/mL vs (1.26±0.42)ng/mL, P<0.01].结论 瘦素及其受体基因多态性与原发性肝癌密切相关,可能参与肝癌的发生发展.     

瘦素受体基因Gln223Arg变异与浙南地区2型糖尿病的相关性研究

目的 研究瘦素受体Gln223Arg基因多态性与2型糖尿病(T2DM)的关系.方法 运用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法测定无亲缘关系的336例浙南地区汉人的瘦素受体基因Gln223Arg的基因型(其中T2DM合并肥胖组121例,T2DM非肥胖组104例,正常对照组111例),并分析Gln223Arg基因多态性与糖尿病的关系.结果 ① T2DM肥胖组Gln223Arg基因型GG、GA及AA的频率分别为0.645、0.347和0.008;G和A等位基因频率分别为0.818和0.182;T2DM非肥胖组基因型GG和GA的频率分别为0.769、0.231;G和A等位基因频率分别为0.885和0.115;正常对照组基因型GG、GA及AA的频率分别为0.802、0.189和0.009;G和A等位基因频率分别为0.896和0.104.②T2DM合并肥胖组A、G等位基因分布频率与正常对照组比较差异有显著性(P＜0.05),非肥胖组与正常对照组比较无明显差异(P＞0.05).结论 浙南地区汉族人群存在瘦素受体基因Gln223Arg变异,它可能是该地区人群T2DM合并肥胖患者的遗传易感标记,A等位基因与T2DM发病有一定关系.     

瘦素受体基因Gln223Arg多态性与脑卒中相关性的研究

目的探讨瘦素受体(leptin receptor,LR)基因Gln223Arg位点多态性与脑卒中的相关性。方法采用聚合酶链反应-限制性片段长度多态性分析法检测50例脑卒中患者和50例正常对照者的LR基因Gln223Arg位点多态性,同时记录受试者年龄、性别,并测定血糖、胆固醇(CHO)、低密度脂蛋白(LDL)、收缩压和舒张压等临床指标进行对比分析。结果脑卒中组的瘦素受体基因G和A等位基因频率分别为74.0%和26.0%,正常对照组分别为84.0%和16.0%,两者比较差异有统计学意义(P<0.05)。与对照组基因型比较,基因型中含有等位基因A的各临床指标要高于对照组。结论 LR基因Gln223Arg位点的A等位基因会增加脑卒中的发病风险。     

瘦素受体基因Gln223Arg多态性与非酒精性脂肪性肝病的关系

目的 探讨瘦素受体基因多态性与非酒精性脂肪肝患者临床表型间的关系.方法 以非酒精性脂肪肝患者和正常对照人群为研究对象,应用聚合酶链反应及限制性片段长度多态性方法(PCR-RFLP),对167例中国人(包括85例非酒精性脂肪肝患者和82例正常对照)的瘦素受体基因Gln223Arg进行研究,同时进行临床参数的检测.结果 (1)非酒精性脂肪肝患者和正常对照组人群中Gln223Arg基因型频率和等位基因频率差异无显著性(P>0.05).(2)非酒精性脂肪肝男性患者中AA AG基因型者TC、BMI高于GG基因型(P<0.05).(3)进一步用Logistic回归分析发现:在非酒精性脂肪肝男性患者中该基因变异与TC相关(P=0.019).结论 非酒精性脂肪肝男性患者瘦素受体基因Gln223Arg多态性与TC水平相关.瘦素受体基因Gln223Arg可能参与非酒精性脂肪肝的脂质代谢.     

瘦素受体基因多态性与云南地区高血压合并肥胖的相关性

目的 探讨瘦素受体(LEPR)基因多态性与云南地区汉族人口高血压合并肥胖的相关性.方法 选取云南地区汉族高血压病住院患者283例,同期选取正常对照组153例.将高血压组以体质指数(BMI)≥28 kg/m2划分为肥胖高血压组162例和单纯高血压组121例两个亚组.运用聚合酶连反应限制性片段长度多态性(PCRRELP)方法测定LEPR基因Gln223Arg和Lys109Arg多态性.采用彩色超声诊断仪测定颈动脉内膜中膜厚度(CIMT).结果 LEPR基因Gln223Arg基因型频率和等位基因频率在高血压组和对照组之间分布有统计学意义(P＜0.01); LEPR基因Lys109Arg基因型频率和等位基因频率在高血压组和对照组之间分布无统计学意义(P＞0.05).LEPR基因Gln223Arg等位基因A的频率在肥胖高血压明显高于单纯高血压组(P＜0.01),并且有着更厚颈动脉内膜中膜厚度(P＜0.05).Lys109Arg基因型频率在肥胖高血压组临床资料比较中差异无统计学意义.结论 LEPR基因Gln223Arg与高血压合并肥胖明显相关;且A等位基因是高血压合并肥胖人群发生动脉粥样硬化的危险因素;Lys109Arg多态性与高血压及各项临床特征比较无明显相关.     

白细胞介素6受体基因多态性与代谢综合征的相关性研究

探讨白细胞介素6受体(IL-6R)基因启动子- 183A/G(rs4845617)和外显子9Asp358Ala( rs8192284 A/C)多态性与代谢综合征(MS)的相关性.结果显示IL-6R基因rs8192284A/C多态性在MS组AA基因型频率和A等位基因频率高于正常对照组(P＜0.05或P＜0.01),携带A等位基因的患者发生MS的风险是C等位基因的1.643倍(95％CI 1.163 ～2.320,P＜0.01);而-183A/G三种基因型频率和等位基因频率差异无统计学意义(P＞0.05).提示IL-6R基因Asp358Ala多态可能与中国国人MS相关.     

The Gln223Arg polymorphism in the leptin receptor is associated with familial combined hyperlipidemia

OBJECTIVE: Familial combined hyperlipidemia (FCH) is characterized by elevated levels of total cholesterol (TC), triglycerides (TG) and apolipoprotein B (apo B) and is associated with premature cardiovascular disease (CVD). Other features of FCH are obesity and insulin resistance. Serum leptin levels have also been associated with obesity, insulin resistance and atherosclerosis. Leptin exerts its effect through the leptin receptor (LEPR). The aim of this study is to determine whether the Gln223Arg polymorphism in the LEPR gene contributes to FCH and its associated phenotypes. METHODS: The study population consists of 37 families, comprising 644 subjects, of whom 158 subjects were diagnosed as FCH. The FCH diagnosis was based on plasma TC and TG levels, adjusted for age and gender, and absolute apo B levels, according to our recently published nomogram. The Gln223Arg polymorphism was studied by restriction fragment length polymorphism-PCR. RESULTS: Carriers of one or two Arg alleles had an increased risk of FCH, compared to subjects homozygous for the Gln allele (OR=1.6 [95% CI 1.0-2.4]). A difference in high-density lipoprotein cholesterol (HDL-c) levels was present between carriers and non-carriers of an Arg allele, 1.21 vs 1.28 mmol/l, respectively (P=0.04), but no differences in obesity, insulin resistance and other lipid parameters were found. CONCLUSION: The Gln223Arg polymorphism in the LEPR gene is associated with FCH, which is supported by a significant association between HDL-c levels and the LEPR gene.     

Leptin and leptin receptor gene polymorphisms in obstructive sleep apnea syndrome

BACKGROUND: Obstructive sleep apnea is common in obese people. Leptin is an adipocyte-derived signaling factor that has an important role in metabolic control. There is growing evidence that leptin regulation is altered in obstructive sleep apnea syndrome (OSAS). The aim of this study was to investigate the relation between polymorphisms of the leptin and leptin receptor (LEPR) genes and OSAS. METHODS: The study population consisted of 130 patients with OSAS and 50 healthy control subjects. All the subjects were Japanese. Diagnostic polysomnography was performed in all patients and control subjects. A highly polymorphic tetranucleotide repeat polymorphism in the 3'-flanking region of the leptin gene and three single nucleotide polymorphisms (SNPs) [Lys109Arg (A/G) in exon 4, Gln223Arg (A/G) in exon 6, and Lys656Asn (G/C) in exon 14] in the LEPR gene were examined. RESULTS: There were no significant differences in allelic frequencies and genotype distributions of the examined polymorphisms of the leptin and LEPR genes between OSAS patients and control subjects. For the LEPR gene, the wild-type alleles of the Gln223Arg and Lys656Asn SNPs had a marginally significant effect on mild OSAS, which was defined as an apnea-hypopnea index from 10 and 20 events/h in the dominant model. CONCLUSIONS: The tetranucleotide repeat polymorphism of the leptin gene and the Lys109Arg, Gln223Arg, and Lys656Asn SNPs in the LEPR gene were not associated with OSAS in the Japanese population. Further studies are required to confirm the association of the wild types of Gln223Arg and Lys656Asn SNPs with the severity of OSAS.     

Association analysis of the Gln223Arg polymorphism in the human leptin receptor gene, and traits related to obesity in Mexican adolescents

Polymorphisms of leptin receptor (LEPR) may contribute to a common form of obesity and, as a consequence, obesity-related diseases. We evaluated the potential role of genetic variation at the LEPR gene in heart sympathetic activity and other traits related to obesity in Mexican adolescents. Adolescents aged between 12 and 17 years, with steady body weight for the last 3 months were included. We evaluated anthropometric measurements, blood pressure, seric glucose, insulin, leptin levels, heart sympathetic activity (by electrocardiograph monitoring at rest), and the Gln223Arg and Pro1019Pro LEPR polymorphisms in each subject. In total, 103 adolescents (55 obese and 48 nonobese) were included. The group of obese adolescents showed higher sympathetic activity, blood pressure, glucose, insulin, and leptin levels. The genotype frequencies for the two polymorphisms were found to be in Hardy-Weinberg equilibrium. There was no difference in the genotype frequencies for Gln223Arg or Pro1019Pro polymorphisms between obese and nonobese adolescents. However, there was a higher prevalence of Gln223 allele among subjects with higher insulin levels (0.72 vs 0.57; P = 0.04 for adolescents with insulin levels higher and lower than 100 pmol/l, respectively). According to Gln223Arg polymorphism, those with Gln allele (Gln/Gln and Gln/Arg) had higher heart sympathetic activity, body fat percentage, and leptin levels. To conclude, our results support the hypothesis that Gln223Arg polymorphism of LEPR in Mexican adolescents is associated with haemodynamic and metabolic disturbances related to obesity.     

慢性阻塞性肺疾病伴营养不良患者瘦素受体基因Gln223Arg多态性研究

目的探讨瘦素受体基因Gln223Arg多态性与慢性阻塞性肺疾病伴营养不良的关系。方法观察158例COPD临床稳定期老年患者及108例健康对照者,并根据体重指数（BMI）、理想体重百分比（NW％）、三头肌皮皱厚度（TSF）、上臂中点臂围（MAC）、血清白蛋白（ALB）、总淋巴细胞（LYM）等营养参数,将COPD组分为营养不良组（COPD1组）66例,COPD非营养不良组（COPD2组）92例。用酶联免疫吸附试验（ELISA）法测定血清瘦素水平,采用聚合酶链式反应及连接酶检测反应方法（PCR—LDR）测定158例COPD患者与108例对照组的瘦素受体基因Gln223Arg多态性的基因型。结果COPD营养不良组Gln223Arg基因型GG、GA及AA的频率分别为0．924、0．061和0．015,G和A等位基因频率分别为0．955和0．045;COPD非营养不良组Gln223Arg基因型GG、GA及AA的频率分别为0．783、0．206和0．011,G和A等位基因频率分别为0．886和0．114;对照组Gln223Arg基因型GG、GA及AA的频率分别为0．769、O．222和0．009,G和A等位基因频率分别0．88和0．12;COPD1组Gln223Arg基因型及等位基因频率与COPD2组和对照组比较差异有显著性;COPD2组和对照组比较差异无显著性。不同基因表型血清瘦素水平GG型低于A／G型＋AA型（40．08±17．53ng／mLVS44．35±16．95ng／mL）,但差异无统计学意义。结论瘦素受体基因Gln223Arg多态性可能与COPD营养不良有关。     

瘦素受体基因多态性与高血压病及其临床代谢特征的相关性研究

目的探讨瘦素受体（LepR）基因多态性与高血压患者及临床代谢特征的相关性。方法选取来自上海、南京地区汉族高血压患者239例,根据体重指数（BMI）是否≥24kg／m。分为超重高血压组154例和单纯高血压组85例,正常人（对照组）141例。运用聚合酶链反应-限制性片段长度多态性（PCR—RFLP）方法测定LepR摹因位点Gln223Arg和Lys109Arg的突变情况。结果位点Gln223Arg、Lys109Arg各基因型频率在高血压组和对照组分布未见明显差异,位点Gln223Arg等位基因G的频率存超重高血压高于单纯高血压组。高血压组临床代谢特征比较,Lys109Arg含A等位基因者（基因型AA＋AG）低密度脂蛋白胆固醇、空腹血糖、餐后血糖高于不含A等位基因者（基因型GG）。结论位点Gln223Arg和Lysl09Arg的变异与高血压无明显相关,但位点Gln223Arg的变异与肥胖相关,Lysl09Arg位点的变异与高血压患者糖代谢、脂代谢异常相关。     

瘦素受体基因Gln223Arg变异与上海地区糖尿病患者代谢紊乱及？…

研究瘦素受体基因Ｇｌｎ２２３Ａｒｇ变异与Ⅱ型糖尿病代谢紊乱及其合并高血压的关系。方法运用聚合酶链反应－限制性片段长度多态性方法测定无亲缘关系,且有完整临床资料的３５９例上海地区汉人的瘦素受体基因Ｇｌｎ２２３Ａｒｇ变异的基因型。