青海省妊娠高血压综合征患者瘦素基因启动子区G-2548 A单核苷酸的多态性

目的探讨青海省妊娠高血压综合征(PIH)与瘦素基因启动子区单核苷酸多态性的关系。方法选择青海省PIH患者130例,正常妊娠对照组135例,应用聚合酶链反应-限制性内切酶片段长度多态性(PCRRFLP)方法,分析PIH患者和对照组瘦素基因G-2548 A多态性分型并测序验证。结果 PIH组基因型频率GG型、GA型和AA型分别为53.1%、40%和6.9%,对照组分别为60%、34.1%和5.9%。PIH组和对照组瘦素基因G-2548 A位点等位基因A和G频率分布具有差异性(P0.05),妊娠高血压综合征组G等位基因频率高于对照组(χ2=4.21,P0.05,OR=0.66,95%CI=0.45~0.99)。结论青海省瘦素基因G2548位点G/A基因多态性与其妊娠高血压的易感性有关。G等位基因可能为妊娠高血压综合征的易感基因,A等位基因可能为妊娠高血压综合征的保护基因。     

瘦素受体基因Gln223Arg位点多态性与哮喘和代谢综合征之间关系的研究北大核心CSCD

目的:探讨瘦素受体基因Gln223Arg位点多态性与哮喘和代谢综合征之间的关系。方法:选择120例哮喘病人(A)、92例代谢综合征病人(M)、54例哮喘合并代谢综合征病人(A+M)和81例健康对照者(NC),其中哮喘组根据肺功能进一步分为轻-中度哮喘组和重度哮喘组。应用聚合酶链反应-限制性内切酶片段长度多态性(PCR-RFLP)方法测定所有受试者瘦素受体基因Gln223Arg位点基因型,ELISA法检测血清瘦素浓度,同时测定所有受试者BMI、血压、肺功能及空腹血糖。结果:(1)代谢综合征组和哮喘合并代谢综合征组AA+AG基因型和A等位基因频率较健康对照组显著性增高(P<0.05);(2)哮喘组中重度持续组AA+AG基因型和A等位基因频率较健康对照组显著增高(P<0.05);(3)AA+AG基因型的血浆瘦素浓度、MBI、收缩压与GG基因型比均显著升高,FEV1%、FEV1/FVC明显下降(P<0.05)。结论:瘦素受体Gln223Arg位点基因多态性与哮喘和代谢综合征具有相关性,其中A等位基因可能通过瘦素抵抗诱导哮喘和代谢综合征的发生,是哮喘和代谢综合征的共同遗传易感因子。     

瘦素基因-2548A/G和瘦素受体基因Gln223Arg位点多态性与哮喘和代谢综合征的关系

目的:研究瘦素基因-2548A/G和瘦素受体基因Gln223Arg位点多态性与哮喘和代谢综合征的关系。方法:选取82例哮喘合并代谢综合征病人(A+M)、114例哮喘病人(AS)、100例代谢综合征病人(MS)以及96例健康对照者(NC)。根据肺功能将AS组分为轻度AS和中重度AS,采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)法分析所有受试者瘦素基因-2548A/G和瘦素受体基因Gln223Arg位点单核苷酸多态性及基因型,并比较不同组之间这两个基因位点和多态性之间的差异。结果:1不同组间生化指标有差异(P均<0.05);2瘦素基因-2548A/G位点多态性:MS、A+M和中重度AS组与NC相比AA基因型及A等位基因频率显著升高(P均<0.05);3瘦素受体基因Gln223Arg位点多态性:MS与NC和AS相比AG+AA基因型及A等位基因频率显著升高(P均<0.05),A+M与AS相比A等位基因频率显著升高(P<0.05),AS组、轻度AS组和中重度AS组与NC组相比均没有差异(P均>0.05)。结论:瘦素基因-2548A/G多态性与哮喘和代谢综合征都有一定的相关性,其A等位基因可能是代谢综合征的致病基因,而且与哮喘严重程度相关;瘦素受体基因Gln223Arg A等位基因可能是代谢综合征的致病基因,却与哮喘无关。     

瘦素受体基因Gln223Arg 位点多态性与哮喘和代谢综合征之间关系的研究

目的:探讨瘦素受体基因Gln223Arg 位点多态性与哮喘和代谢综合征之间的关系。方法:选择120 例哮喘病人(A)、92 例代谢综合征病人(M)、54 例哮喘合并代谢综合征病人(A+M)和81 例健康对照者(NC),其中哮喘组根据肺功能进一步分为轻-中度哮喘组和重度哮喘组。应用聚合酶链反应-限制性内切酶片段长度多态性(PCR-RFLP)方法测定所有受试者瘦素受体基因Gln223Arg 位点基因型,ELISA 法检测血清瘦素浓度,同时测定所有受试者BMI、血压、肺功能及空腹血糖。结果: 代谢综合征组和哮喘合并代谢综合征组AA+AG 基因型和A 等位基因频率较健康对照组显著性增高(P<0.05); 哮喘组中重度持续组AA+AG 基因型和A 等位基因频率较健康对照组显著增高(P<0.05); AA+AG 基因型的血浆瘦素浓度、 MBI、收缩压与GG 基因型比均显著升高,FEV1%、FEV1/ FVC 明显下降(P<0.05)。结论:瘦素受体Gln223Arg 位点基因多态性与哮喘和代谢综合征具有相关性,其中A 等位基因可能通过瘦素抵抗诱导哮喘和代谢综合征的发生,是哮喘和代谢综合征的共同遗传易感因子。     

瘦素及瘦素受体基因多态性与重度子痫前期发病的相关性

目的 探讨血清瘦素水平和瘦素受体基因(leptin receptor gene,LEPR)Pro1019Pro (G1019A)和Gln223Arg(A223G)多态性与重度子痫前期发病的相关性.方法 采用聚合酶链反应-限制性片段长度多态性方法检测207例重度子痫前期和252名正常妊娠孕妇(对照组)LEPR基因G1019A和A223G多态性;ELISA法检测血清瘦素水平.结果 (1)重度子痫前期组患者血清瘦素水平显著高于正常对照组孕妇,新生儿体重明显低于对照组,早产儿发生率显著高于对照组(P＜0.01).(2) LEPR基因G1019A多态性GA基因型和G等位基因频率重度子痫前期组(33.8％和20.3％)显著高于对照组(19.8％和15.1％)(P＜0.01),携带GA型和G等位基因孕妇发生重度子病前期的风险较AA型和A等位基因个体分别增加2.04倍(95％CI:0.77～5.42)和1.43倍(95％CI:1.02～2.01).(3)LEPR基因A223G多态性AG基因型和A等位基因频率分布重度子痫前期组(19.3％和12.6％)明显低于对照组(34.5％和19.2％)(P＜0.01),携带AG型和A等位基因孕妇发生重度子痫前期的风险较GG型和G等位基因个体分别降低0.46倍(95％CI:0.30～0.71)和0.60倍(95％ CI:0.42～0.87).(4)LEPR G1019A和A223G多态性“1019AA+223AG”联合基因型频率重度子痫组(6.8％)显著低于对照组(24.6％)(P＜0.01),携带者发生重度子痫前期的风险较其它联合基因型个体低0.22倍,95％CI:0.12～0.39;而“1019GA+223GG”联合基因型频率重度子痫前期组(22.2％)显著高于对照组(11.9％)(P＜0.05),携带者发生重度子病前期的风险增加2.10倍,95％CI:0.78～3.45.(5)LEPR基因G1019A和A223G多态性各基因型之间收缩压、舒张压、体重指数和血清瘦素水平比较差异均无统计学意义(P＞0.05).结论 血清中高浓度的瘦素水平和LEPR基因G1019A、A223G多态性与重度子痫前期发病可能存在关联,血清瘦素水平与LEPR基因G1019A和A223G多态性无关;G1019A GA基因型和“1019GA+ 223GG”联合基因型可能是重度子痫前期的易感基因型.     

武汉地区IGT患者瘦素受体基因变异与高血压关系的研究

目的:研究瘦素受体(LR)基因Gln223Arg变异与武汉地区糖耐量减低(IGT)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572例(包括252例糖耐量正常者及320例IGT患者)武汉地区汉族人群的LR基因Gln223 Arg变异频率。同时测血糖、血脂、身高、体重,按公式计算体重指数(BMI)。结果:(1)IGT合并高血压病组Gln 223 ArgAA、AG和GG基因型及A、G等位基因频率与正常对照组比较有非常显著性差异(均P<0.01);(2)男性IGT合并高血压病组与女性IGT合并高血压病组Gln 223 Arg变异基因型及等位基因比较具有显著统计学差异(均P<0.01);(3)IGT合并高血压病组Gln 223 Arg变异与收缩压和舒张压显著正相关(r分别为0.91和0.90,均P<0.05),A等位基因与肥胖型IGT合并高血压男性患者收缩压和舒张压呈正相关,携带A等位基因的肥胖型男性IGT其高血压发生的比数比(OR)为3.88(95%CI为2.77～5.44)。结论:LR基因Gln 223 Arg变异与肥胖男性IGT合并高血压相关,且与收缩压和舒张压均相关。     

瘦素受体基因Lys109Arg多态性与温州地区高血压合并肥胖的相关性研究

目的了解温州地区汉族人群瘦素受体Lys109Arg基因型分布;探讨该基因多态性与高血压合并肥胖的关系。方法运用序列特异性引物-聚合酶链式反应技术(PCR-SSP)测定无亲缘关系的381例温州地区汉族人群的瘦素受体基因Lys109Arg多态性(正常对照组111例,高血压病合并肥胖148例,高血压病非肥胖122例)。结果高血压合并肥胖组瘦素受体基因Lys109Arg的AA、AG和GG基因型频率分别为0.020、0.135和0.845,等位基因A和G频率分别为0.088和0.912;高血压合并非肥胖组基因型频率分别为0.049、0.246和0.705,基因型A和G等位基因频率分别为0.172和0.828;正常对照组基因型表达频率分别为0.027、0.315和0.658,A和G等位基因频率分别为0.185和0.815;Lys109Arg位点多态性的分布频率在对照组和病例组间差异有统计学意义(χ2=7.688,P0.05),且G等位基因频率在高血压合并肥胖患者中显著高于非肥胖组(χ2=8.634,P0.05)。结论瘦素受体基因Lys109Arg多态性与温州地区汉族人群高血压合并肥胖相关。     

瘦素受体基因3057位G→A变异与妊娠高血压综合征的关系

目的探讨瘦素受体基因（Leptin receptor gene,LEPR）20外显子3057位核苷酸G→A变异与妊娠高血压综合征（妊高征,PIHs）关系。方法应用PCR-RFLP法检测了106例妊高征患者（妊高征组）和98例正常妊娠孕妇（对照组）LEPR基因3057位核苷酸G→A变异。结果妊高征组LEPR基因型频率分布：GG型为2.8%,GA型为16.1%,AA型为81.1%;妊高征组AA基因型频率和A等位基因频率（81.1%和89.1%）高于对照组孕妇（74.5%和85.2%）,但无统计学意义（P〉0.05）;携带A等位基因和AA基因型的孕妇发生PIHs的相对风险OR值分别为1.43（95%CI：0.79～2.56）和1.72（95%CI：0.28～10.75）（P〉0.05）。结论LEPR基因3057位G→A变异与潍坊地区汉族人群PIHs的发病无明显相关性。     

Ⅱ型糖尿病患者瘦素受体基因变异与肥胖及高血压的相关性研究

目的　探讨Ⅱ型糖尿病患者瘦素受体基因Gln2 2 3Arg变异与肥胖及高血压之间的相关性。方法　采用PCR -RELP方法分析了 1 84例无锡地区Ⅱ型糖尿病患者及 86例正常对照组Gln2 2 3Arg变异频率的分布情况。结果　 (1 )整个被检测的Ⅱ型糖尿病人群中Gln2 2 3Arg变异频率与正常对照组比较经统计学处理没有显著性差异 ;(2 )Ⅱ型糖尿病患者中的正常体重组A、G等位基因的分布频率与超重组分布频率的比较亦无显著性差异 ;(3)在Ⅱ型糖尿病患者中高血压组和非高血压组之间存在非常显著的A、G等位基因的分布频率差异 (P值 <0 0 0 5)。结论　A等位基因与Ⅱ糖尿病患者的肥胖无一定的关系而与其高血压的发病相关     

瘦素受体基因Gln223Arg多态性与2型糖尿病合并高尿酸血症患者的关系以及二甲双胍治疗效果的评价

目的 评价瘦素受体基因Gln223Arg多态性与2型糖尿病(type 2 diabetes,T2DM)合并高尿酸血症(hyperuricemia,HUA)患者的关系以及二甲双胍治疗效果.方法 取2018年3月至2019年12月我院收治的160例初诊T2DM患者,根据T2DM患者是否合并HUA分为T2DM组(n=80)和合并组(n=80).通过PCR限制性片段长度多态性(PCR-RELP)法测定瘦素(LEP)受体基因Gln223Arg多态性分布频率,并使用多因素非条件Logistic回归对T2DM合并HUA患者的危险因素进行分析,同时对T2DM合并HUA患者进行二甲双胍治疗,分析二甲双胍疗效与各基因型的关系.结果 两组性别、年龄、总胆固醇(TC)、高密度脂蛋白(HDL-C)比较,组间差异无统计学意义(P>0.05);合并组吸烟史、冠心病史、糖尿病病程、体质量指数(BMI)、三酰甘油(TG)、低密度脂蛋白(LDL-C)、糖化血红蛋白(HbA1c)、胰岛素抵抗指数(HOMA-IR)、尿酸(UA)、LEP均高于T2DM组(P<0.05);T2DM组和合并组瘦素受体Gln223Arg各基因型的期望值和观察值比较,P均>0.05,符合Hardy-Weinberg平衡定律;与T2DM组对比,合并组Gln223Arg基因位点AA型、AG型显著降低(P<0.05),而GG型显著升高(P<0.05);行多因素Logistic回归分析,结果显示,T2DM合并HUA患者基因型GG、吸烟史、冠心病史、糖尿病病程、BMI、TG、LDL-C、HbA1c、HOMA-IR、尿酸、LEP是危险因素;GG型、AG型FPG、2hPBG、HbA1降低幅度均低于AA型(P<0.05),而GG型FPG、2hPBG、HbA1降低幅度均低于AG型(P<0.05).结论 T2DM患者携带GG基因型可能是HUA的易感因素,且瘦素受体基因Gln223Arg多态性位点AA型患者对二甲双胍敏感,降糖疗效较好.     

ORIGINAL ARTICLE: Leptin Gene (TTTC)n Microsatellite Polymorphism as well as Leptin Receptor R223Q and PPARγ2 P12A Substitutions are not Associated with Hypertensive Disorders in Pregnancy

Citation Wiedemann A, Vocke F, Fitzgerald JS, Markert UR, Jeschke U, Lohse P, Toth B. Leptin gene (TTTC)_n microsatellite polymorphism as well as Leptin receptor R223Q and PPARγ2 P12A substitutions are not associated with hypertensive disorders in pregnancy. Am J Reprod Immunol 2010; 63: 310–317 Problem Pregnancy‐induced hypertension (PIH) affects up to 15% of all pregnancies. Disturbed placentation is one factor associated with PIH. Leptin and peroxisome proliferator activator receptors (PPAR) seem to play an important role in placentation, fetal development, and blood pressure regulation. Therefore, we investigated polymorphisms in the genes encoding leptin, the leptin receptor, and PPARγ2 in patients with PIH. Method of study In this retrospective case–control study, 103 patients with PIH [gestational hypertension (GH) n = 39; preeclampsia n = 27; eclampsia n = 5; HELLP n = 32] and 100 controls were analyzed for the LEP tetranucleotide repeat (TTTC)_n and the leptin receptor (LEPR) R223Q and PPARγ2 P12A substitutions. Statistical analysis was performed using the chi‐square, Mann–Whitney U‐, and Kruskal–Wallis tests (P < 0.05 significant). Results The frequency of the three possible genotypes did not differ significantly between patients and controls [LEP (TTTC)_n: P = 0.43; LEPR R223Q: P = 0.94; PPARγ2 P12A: P = 0.94]. However, postpartal diastolic blood pressure of PIH patients was significantly higher in homozygous carriers of the LEPR Q223‐encoding allele as compared with patients carrying the wild‐type allele (P < 0.01). Conclusion Hypertensive disorders in pregnancy were not associated with the LEP, LEPR, and PPARγ2 polymorphisms studied. The role of other variations in the LEP and PPAR genes in the pathophysiology of PIH and in exacerbations are the objective of ongoing research.     

内皮型一氧化氮合酶基因G894T多态性与青海省汉族妊娠高血压综合征的相关性

目的探讨内皮型一氧化氮合酶(eNOS)G894T基因多态性与青海省汉族妊娠高血压综合征(PIH)的相关性。方法采用限制性片段长度多态性聚合酶链反应(PCR-RFLP)方法对138名妊娠高血压综合征患者和135名正常孕妇e NOS基因G894T多态性进行分型,并测序验证。结果妊娠高血压综合征组基因型频率野生型(GG)、杂合子型(GT)和突变纯合子型(TT)分别为17.4%、82.6%、0;对照组分别为0、95.6%、4.4%,两组基因型频率分布有差异(P0.05)。妊娠高血压综合征组e NOS等位基因频率G、T分别为58.7%、41.3%;对照组分别为47.8%、52.2%,两组比较差异有统计学意义(P0.05),妊娠高血压综合征组G基因频率高于对照组。结论e NOS基因G894T多态性可能与青海省汉族妊娠高血压综合征有关,G等位基因可能为妊娠高血压综合征的易感基因(OR=1.229,95%CI:1.048~1.441),T等位基因可能为妊娠高血压综合征的保护基因。携带GG基因型的孕妇可作为青海省妊娠高血压综合征的易感人群。     

A polymorphism in the leptin receptor gene at position 223 is associated with growth hormone replacement therapy responsiveness in idiopathic short stature and growth hormone deficiency patients

We hypothesized that responses to growth hormone (GH) therapy by idiopathic short stature (ISS) and growth hormone deficiency (GHD) patients were associated with single nucleotide polymorphisms (SNPs) in the leptin (LEP) and leptin receptor (LEPR) genes. We retrospectively enrolled ISS (n = 32) and GHD (n = 38) patients and forty healthy age-and gender-matched children. They were genotyped for the LEP promoter at nt.-2548, and LEPR K109R and LEPR Q223R polymorphisms. Clinical and laboratory variables were determined before and after 2 years of GH treatment. ISS patients with G/A or A/A genotypes of the LEPR Q223R SNP had a significantly higher height velocity (cm/y) than ISS patients with the G/G genotype at 2 years after GH treatment. For GHD patients, G/A or A/A genotype of the LEPR K109R SNP was associated with higher body weight, higher BMI, and higher weight velocity than patients with the G/G genotype before GH treatment, but not after GH treatment. G/A or A/A genotype of the LEPR Q223R SNP was associated with a significantly higher body weight, higher height velocity before treatment, but not after GH treatment. G/A or A/A genotype of the LEPR Q223R SNP was associated with a significantly higher weight velocity before treatment, but a significantly lower weight velocity was found at 2 years after GH treatment. These results suggest LEPR Q223R SNP (rs1137101) is associated with outcomes of GH replacement therapy in ISS and GHD patients.     

Structure and sequence variation at the human leptin receptor gene in lean and obese Pima Indians

The cloning of human and mouse cDNAs from brain that encode high affinity leptin receptors was recently reported. We have physically localized the human leptin receptor gene (LEPR) to a region at 1p31, between the anonymous microsatellite markers D1S515 and D1S198. The genomic structure of the human leptin receptor gene, corresponding to the published human brain cDNA sequence, spans over 70 kb and includes 20 exons. Since the leptin receptor gene is a candidate gene for obesity, and because of its proximity to D1S198, a marker previously linked to insulin secretion, the LEPR gene was sequenced in 20 non- diabetic Pima Indians chosen for extremes in percent body fat and in their acute insulin response to intravenous glucose. Seven polymorphic sites were identified. Two of these polymorphisms, Lys109Arg and Gln223Arg, are amino acid substitutions in the extracellular domain of the leptin receptor, one polymorphism is a silent substitution, and four occur in non-coding regions of the leptin receptor. Four of these sites are in linkage disequilibrium with one another. Nucleotides at three noncoding polymorphic sites were found exclusively in obese Pima Indians. This demonstrates an association between variation at the leptin receptor gene and obesity in humans.      

Serum Leptin Levels,Leptin Receptor Gene (LEPR) Polymorphism,and the Risk of Systemic Lupus Erythematosus in Kashmiri Population

The study is conducted to evaluate relationship between LEPRQ223R (Gln?>?Arg) polymorphism, serum leptin levels, soluble leptin receptor (SOb-R) levels and SLE risk in Kashmiri population.LEPR genotyping was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in 100 unrelated SLE patients and equal number of healthy control subjects. Leptin and SOb-R levels were measured by ELISA assays. The present study showed higher frequency of variant genotype (AG?+?GG) in cases compared to controls [OR?=?2.52, CI?=?1.18–5.35, p?=?0.03]. Moreover the rare (G) allele was significantly more predominant in cases than controls [OR?=?1.49, p?=?0.04]. Interestingly a positive association between the variant genotype and the development of arthritis [OR?=?11.8, CI?=?1.6–85.1, p?=?0.002] and an inverse association with cardiac disorder [OR?=?0.09, CI?=?0.02–0.46, p?=?0.001] was observed in this study. Furthermore the study showed significant differences of leptin levels in SLE patients and controls (23.9?±?19.5 vs 14.8?±?10.4, p?<?0.001). SLE patients in the highest quartile leptin levels (≥32.5?ng/mL) were significantly more likely to have higher BMI (p?=?0.001) and increased risk of developing arthritis (p?=?0.02). Furthermore positive association was observed between the variant genotype(AG?+?GG) and leptin levels (p?=?0.001) in SLE patients. Thus, it is evident from our study that LEPRQ223R polymorphism and elevated leptin levels are associated with increased susceptibility of SLE in Kashmiri population.