β2-肾上腺素能受体多态性/单倍型与支气管哮喘表型的相关性

目的 研究β2-肾上腺素能受体基因的多态性/单倍型与支气管舒张剂的反应性及血清免疫球蛋白E的负对数(lgIgE)间的关系.方法 2006年2月至2007年2月采用DNA测序法测定了201例哮喘患者(哮喘组)和276名健康对照者(健康对照组)的β2-AR基因5个位点(-47、-20、46、79、252)的基因型并确定其单倍型.统计学处理采用SPSS 11.5软件.以拟和优度的x2检验计算各位点基因型频率是否符合Hardy-Weinberg平衡.5个位点基因型的频率比较采用卡方检验,位点间的连锁不平衡采用确切概率法,不同基因型及单倍型与定量指标间的比较采用方差分析.如果方差分析有统计学意义,则用LSD方法对各组间的值进行两两比较.结果 哮喘组中Arg16Arg16基因型患者的支气管舒张剂反应性为(13±4)L,与Arg16Gly16基因型[(7±3)L]及G1y16Gly16基因型[(7±3)L]比较差异有统计学意义(F=81.55,P＜0.01);在哮喘组6种单倍型中,单倍型Arg16Gln27/Arg16Gln27的△FEV1最高[(13.4±3.5)L],与其他种单倍型[Gly16Gln27/Gly16Gln27(6.4±0.6)L、Gly16Glu27/Gly16Glu27(7.6±3.1)L、Gly16Gln27/Gly16Glu27(6.9±3.5)L、Gly16Gln27/Arg16Gln27(7.2±3.3)L及Gly16Glu27/Arg16Gln27(7.9±2.7)L]比较差异有统计学意义(F=32.55,P＜0.01);哮喘组中Gln27Gln27基因型患者的血清lgIgE为(2.51±0.33)IU/L,与Gln27Glu27基因型患者的血清lgIgE[(2.30±0.82)IU/L]比较差异有统计学意义(F=3.89,P＜0.05);哮喘组中单倍型Gly16Glu27/Arg16Gln27的血清lglgE最低[(2.13±0.15)IU/L],与其他4种单倍型[Arg16Gln27/Arg16Gln27为(2.56±0.14)IU/L、Gly16Glu27/Gly16Glu27为(2.40±0.16)IU/L、Gly16Gln27/Gly16Glu27为(2.54±1.26)IU/L、Gly16Gln27/Arg16Gln27为(2.48±0.48)IU/L]比较差异有统计学意义(F=3.56,P＜0.01).结论 依据所研究的哮喘表型,无论是β2-AR基因的多态性,还是单倍型均可能影响疾病的表现.     

肝硬化时蛋白质与氨基酸代谢的改变及其临床意义

肝硬化时,机体多处于分解代谢状态,蛋白质合成虽有增加,但仍相对不足。肝硬化患者多有较好的节氮效应。肝硬化时血浆芳香族氨基酸谱(AAA)上升,支链氨基酸(BCAA)和BCAA/AAA 比值减低。肝硬化时可能有BCAA 转运系统的调节异常及分布异常。AAA 水平取决于肝脏损害的程度。AAA 水平高常伴有负氮平衡,BCAA/AAA 比值是判断肝脏损害程度的一个敏感指标。血浆氨基酸谱改变与肝性脑病的程度不相关。     

慢性肝病患者血浆氨基酸模式改变及其临床意义的再探讨

本研究分析91例慢性肝病患者血浆氨基酸水平与肝功能损害的关系。慢性肝炎和按child-pugh计分标准进行肝功能分级的肝硬变患者．其血浆支链氨基酸(BCAA)与芳香氨基酸(AAA)克分子浓度比值(BCAA／AAA)有显著统计学差异。病情稳定的慢性肝炎患者，其BCAA／AAA均大于2．5(n=14)；肝功能A级的肝硬变患者，其比值多数>2．5．有25．6%病例小于2.5(n=39);肝功能B级的肝硬变患者全部病例小于2．5(n=32)．有9．4％病例小于1.0;肝功能C级的肝硬变患者全部病例小于2．5(n=6)，有50％病例小于1．0。上述情况提示BCAA／AAA可怍为慢性肝病患者肝功能改变的一项较敏感和可靠的量化监测指标。     

新疆维吾尔族人β2肾上腺素能受体基因多态性与原发性高血压的相关性

目的探讨β₂肾上腺素能受体（β₂-AR）基因Arg16Gly和Gln27Glu多态性在新疆维吾尔族人原发性高血压（EH）发病中的作用。方法应用TaqMan技术检测了367例新疆维吾尔族EH患者及408例正常血压对照者Arg16Gly和Gln27Glu多态性。结果 Arg16Gly和Gln27Glu多态性在新疆维吾尔族群体中分布均符合Hardy-Weinberg平衡;Arg16GlyGG、AG、AA基因型频率和Gln27GluGG、CG和CC基因型频率在EH组和正常血压组间差异无统计学意义（P>0.05）。EH组和正常血压组间Arg16Gly及Gln27Glu位点的G等位基因频率分别为46.0%、42.5%和22.3%、24.5%,差异无统计学意义（P>0.05）。结论β₂-AR基因Arg16Gly和Gln27Glu多态位点可能不是新疆维吾尔族人群原发性高血压的遗传易感指标。     

CCl_4肝硬变模型大鼠血清氨基酸变化及其意义

作者应用CCl_1、高脂低蛋白复合因素制造大鼠肝硬变模型,测定大鼠血氨基酸水平.结果表明.支链氨基酸(BCAA)水平明显降低,而芳香族氨基酸(AAA)明显增高,BCAA/AAA比值显著增高.这些变化与临床肝硬变患者的变化相一致,因此该模型对研究肝硬变时氨基酸失衡的机制以及筛选临床上行之有效的治疗肝硬变的药物,均有良好的价值.     

β2肾上腺素能受体基因多态性与原发性高血压的相关性研究

目的:检测贵州汉族人群β2 肾上腺素能受体基因Gln27Glu多态性,并探讨其与贵州汉族人群原发性高血压(EH)以及其他心血管病危险因素的关系。方法:选择131例EH患者及40例正常人为对象,通过聚合酶链反应确定基因型,并测定每个对象的体质指数(BMI)、腰围、臀围、腰围/臀围、空腹血三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL- C)、高密度脂蛋白胆固醇(HDL- C)以及LP(α)等。结果:①Gln27Glu多态性的基因型频率和等位基因频率在EH组和对照组间差异无统计学意义 (P>0.05),但 Glu27/Glu、Gln27/Glu基因型频率和Glu27等位基因频率在3级EH组的比例明显高于其在对照组及 1、2 级 EH组的比例(P<0.05);②Glu27/Glu、Gln27/Glu两种基因型个体的TC显著高于 Gln27/Gln基因型个体 (P<0.05),而 BMI、腰围/臀围、TG、LDL- C、HDL- C以及LP(α)等在三种基因型之间差异无统计学意义(P>0.05)。结论:Gln27Glu基因多态性与3级EH及TC有关联。     

β2肾上腺素能受体基因Arg16Gly和Gln27Glu多态性与高海拔地区藏族人群原发性高血压的相关性研究

目的 :检测高海拔地区藏族人群β2肾上腺素能受体(β2-AR)基因Argl6Gly和Gln27Glu多态性,并研究其与原发性高血压的相关性。方法:选择原发性高血压患者(原发性高血压组)385例及正常对照(对照组)297例为研究对象,通过SNa Pshot微测序技术测定其基因型和等位基因,对在两组人群中的频率分布进行对比。结果 :β2-AR基因Argl6Gly和Gln27Glu多态性的基因型和等位基因频率原发性高血压组和对照组间比较差异无统计学意义(P0.05),进一步进行不同性别人群间的对比分析,差异亦无统计学意义(P0.05)。结论:未观察到β2-AR基因Argl6Gly和Gln27Glu多态性与高海拔地区藏族人群原发性高血压的相关性。     

肝病患者氨基酸代谢紊乱的意义及其治疗

许多临床观察和动物实验提示,肝性脑病和多种肝病时氨基酸代谢有明显改变,主要表现为血液中芳香族氨基酸(AAA)如苯丙氨酸和酪氨酸的增多以及支链氨基酸(BCAA)如缬氨酸、亮氨酸和异亮氨酸的减少。BCAA 减少及/或 AAA 增多导致 BCAA/AAA 克分子比值降低。与此同时,蛋氨酸和半胱氨酸等     

β2-AR多态性与慢性阻塞性肺疾病的关系

目的 探讨β2:肾上腺素受体(β2-AR)编码区16、27位点基因多态性与慢性阻塞性肺病(COPD)的关系.方法 通过测序确定49例COPD患者(COPD组)和48例健康查体者(对照组)的基因突变类型,同时测定COPD组的第1秒用力呼气容积占预计值的百分比(FEV1%).结果 β2-AR编码区16、27位点基因频率和等位基因频率在COPD组与对照组问的分布无统计学差异(P＞0.05);16位点基因多态性与FEV1%值显著相关(P＜0.01),Gly/Gly与Arg/Gly基因型患者的FEV1%值低于Arg/AI芎基因型患者.27位点基因多态性与FEV1%值显著相关(P＜0.05),Gln/Gln与Gln/Gh基因型患者的FEV1%值低于Glu/Gh基因型患者.结论 β2-2-AR16、27位点基因多态性可能不是COPD发病的基本原因,但其能够影响COPD患者的肺功能.     

胎肝细胞输注治疗后血浆氨基酸的变化及其与肝功能的关系

本文观察了肝硬化患者输注胎肝细胞后血浆氨基酸和肝功能的变化。治疗组血浆BCAA浓度显著增高,AAA和BCAA/AAA变化不明显;对照组BCAA和AAA均无明显变化。输注后,AAA仍与白蛋白呈负相关,与球蛋白呈正相关;BCAA虽与总胆红素呈负相关,但与白、球蛋白失去相关关系。     

Identification of serum metabolites associated with obesity and traditional risk factors for metabolic disease in Chinese adults

Background and aims

Obesity is a major worldwide health problem and is often associated with many metabolic diseases. Levels of several serum-specific metabolites may be altered in patients with these metabolic diseases. We aimed to investigate the associations of serum metabolite levels with obesity and traditional risk factors for metabolic disease in Chinese individuals.

β2-Adrenergic Receptor Haplotype Linked to Intubation and Mechanical Ventilation in Children with Asthma

Background and aims. Children with asthma and respiratory failure comprise a small but significant subset of children with acute asthma. In addition to clinical and historical factors that have been associated with respiratory failure, there may also be genetic factors that predispose some asthmatic children to intubation and mechanical ventilation. However, this has not previously been assessed in this population. We hypothesized that genetic polymorphisms of the β₂-adrenergic receptor (ADRβ₂) are associated with intubation and mechanical ventilation in children with asthma. Materials and methods. We performed genotyping of the ADRβ₂ in a pooled cohort of 104 children admitted to the intensive care unit (ICU) with a severe asthma exacerbation between 2002 and 2008. Genotype of the ADRβ₂ was compared with intubation for respiratory failure. Results. At amino acid position 16, 33% (n = 34) of children were homozygous for the glycine allele (Gly16Gly), 15% (n = 16) were homozygous for the arginine allele (Arg16Arg), and 52% (n = 54) were heterozygous (Arg16Gly). At amino acid position 27, 54% (n = 56) of children were homozygous for the glutamine allele (Gln27Gln), 8% (n = 8) were homozygous for the glutamic acid allele (Glu27Glu), and 38% (n = 40) were heterozygous (Gln27Glu). The haplotypes at these positions were Arg16Gly–Gln27Gln (29%, n = 30), Arg16Gly–Gln27Glu (22%, n = 23), Gly16Gly–Gln27Glu (16%, n = 17), Arg16Arg–Gln27Gln (16%, n = 17), Gly16Gly–Gln27Gln (9%, n = 9), and Gly16Gly–Glu27Glu (8%, n = 8). Twelve children in this cohort were intubated for respiratory failure. Intubation was not associated with age, obesity, race/ethnicity, or NHBLI asthma classification. However, children with the Arg16Gly–Gln27Gln haplotype were significantly more likely to be intubated and mechanical ventilated (OR = 4.2; 95% CI = 1.2–14.5; p = .036) than children with other haplotypes of the ADRβ₂. When examining the subset of intubated children, those with the Arg16Gly–Gln27Gln haplotype trended towards longer ICU length of stay (329 ± 270 vs. 124 ± 57 hours; p = .09), but this was not statistically significant. Conclusions. Children with the Arg16Gly–Gln27Gln haplotype of the ADRβ₂ were four times more likely to be intubated and mechanically ventilated during severe asthma exacerbations. Genetic factors may influence the development of a more severe asthma phenotype during acute exacerbations.     

Amino acid metabolism during exercise in trained rats: the potential role of carnitine in the metabolic fate of branched-chain amino acids

The influence of endurance training and an acute bout of exercise on plasma concentrations of free amino acids and the intermediates of branched-chain amino acid (BCAA) metabolism were investigated in the rat. Training did not affect the plasma amino acid levels in the resting state. Plasma concentrations of alanine (Ala), aspartic acid (Asp), asparagine (Asn), arginine (Arg), histidine (His), isoleucine (Ile), leucine (Leu), lysine (Lys), methionine (Met), phenylalanine (Phe), proline (Pro), serine (Ser), threonine (Thr), and valine (Val) were significantly lower, whereas glutamate (Glu), glycine (Gly), ornithine (Orn), tryptophan (Trp), tyrosine (Tyr), creatinine, urea, and ammonia levels were unchanged, after one hour of treadmill running in the trained rats. Plasma concentration of glutamine (Glu), the branched-chain keto acids (BCKA) and short-chain acyl carnitines were elevated with exercise. Ratios of plasma BCAA/BCKA were dramatically lowered by exercise in the trained rats. A decrease in plasma-free carnitine levels was also observed. These data suggest that amino acid metabolism is enhanced by exercise even in the trained state. BCAA may only be partially metabolized within muscle and some of their carbon skeletons are released into the circulation in forms of BCKA and short-chain acyl carnitines.     

Complete amino acid sequence of murine beta 2-microglobulin: structural evidence for strain-related polymorphism.

Primary structural analyses of beta 3-microglobulin isolated from the tumor cell lines EL4.BU (derived from a C57BL/6 mouse) and C14 (derived from a BALB/c mouse) have revealed the presence of an amino acid difference at position 85 of this molecule. beta 2-Microglobulin isolated from histocompatibility antigens of EL4.BU has alanine at this position, whereas that from C14 has aspartic acid. Determination of the sequence of these molecules has employed radiochemical methodology that was developed in studies of murine histocompatibility antigens. The sequence obtained in this study is: Ile - Gln - Lys - Thr - Pro - Gln - Ile - Gln - Val - Tyr - Ser - Arg - His - Pro - Pro - Glu - Asn - Gly - Lys - Pro - Asn - Ile - Leu - Asn - Cys - Tyr - Val - Thr - Gln - Phe - His - Pro - Pro - His - Ile - Glu - Ile - Gln - Met - Leu - Lys - Asn - Gly - Lys - Lys - Ile Pro - Lys - Val - Glu - Met - Ser - Asp - Met - Ser - Phe - Ser - Lys - Asp - Trp - Ser - Phe - Tyr - Ile - Leu - Ala - His - Thr - Glu - Phe - Thr - Pro - Thr - Glu - Thr - Asp - Thr - Tyr - Ala - Cys - Arg - Val - Lys - His - Ala/Asp - Ser - Met - Ala - Glu - Pro - Lys - Thr - Val - Tyr - Trp - Asp - Arg - Asp - Met. Comparison of the sequence of murine beta 2-microglobulin to the sequences reported for the homologues from man, rabbit, and guinea pig indicate identities of 68%, 66%, and 61%, respectively.     

Beta 2 Adrenergic Receptor Genetic Polymorphisms in Bronchial Asthma: Relationship to Disease Risk,Severity, and Treatment Response

Background

The β₂-adrenergic receptor gene is one of the most extensively studied genes with respect to asthma prevalence and severity. The Arg16Gly and Gln27Glu polymorphisms in the β₂-adrenergic receptor gene cause changes in the amino acids sequence of the receptor which may cause alteration in response to bronchodilators and the risk of asthma.

Objective

The purpose of the study was to determine the association between β₂-adrenergic receptor gene polymorphisms and asthma risk, severity and response to therapy.

Subjects and Methods

58 asthmatic patients and 38 healthy subjects were included. The β₂-adrenergic receptor polymorphisms genotyping was done using Real-Time polymerase chain reaction.

Results

The allelic frequencies for the Arg16Gly polymorphism were 15.5%, 48.3%, and 36.2% for the homozygous A wild, heterozygous, and homozygous G mutant alleles in asthmatics (P?<?0.01) and 5.3%, 47.4%, and 47.4% in healthy subjects (P?<?0.01). For the Gln27Glu polymorphism, the allelic frequencies for the homozygous C wild, heterozygous and homozygous G mutant alleles were 51.7%, 41.4%, and 6.9% in asthmatics (P?<?0.01) and 44.7%, 39.5%, and 15.8% in healthy subjects (P?<?0.01). The heterozygous Arg16Gly and Gln27Glu were found in most of severe asthma cases (7/13, 53.8% each). While homozygous wild and mutant seemed to be protective and associated with mild disease in both alleles. Finally, 75% of Arg16Gly heterozygous group were good responders (P?<?0.01), 81% of homozygous G mutant were bad responders. For Gln27Glu polymorphism, 60% of C wild group were good responders and 75% of G mutant group were bad responders.

Conclusions

The findings suggest that the Arg16Gly and Gln27Glu polymorphisms in the β2-AR gene are associated with asthma severity and response to therapy and might be used in personalized treatment for these patients in the future. This work is registered in ClinicalTrial.gov with ID: NCT03118869.

     

Beta1 and beta2-adrenergic receptor polymorphisms and idiopathic ventricular arrhythmias

Introduction: Idiopathic ventricular arrhythmias commonly refer to ventricular tachycardia (VT) and/or frequent/monomorphic premature ventricular contractions (PVC) in patients with structurally normal heart. Activation of sympathetic tone has been shown to play an important role in the provocation and maintenance of these arrhythmias. We investigated whether common single nucleotide polymorphisms in the β₁ and β₂‐adrenergic receptors are associated with idiopathic ventricular arrhythmias. Methods: A total of 143 unrelated patients presenting with idiopathic ventricular arrhythmias were prospectively included in a case‐control association study. Patient population was matched by age and gender to the unrelated, healthy control subjects (N = 307). All study subjects were of Turkish (Anatolian Caucasian) descent. Allele and genotype frequencies of the Gly389Arg and Ser49Gly polymorphisms of the β₁‐adrenergic receptor and Arg16Gly, Gln27Glu, and Thr164Ile polymorphisms of the β₂‐adrenergic receptor were compared between patient population and control subjects. The genotype frequencies were in Hardy‐Weinberg equilibrium. Results: Patients with idiopathic ventricular arrhythmias had higher frequency of Arg389Arg genotype (22.4% vs 1.6%, P < 0.001), Arg389Gly49 (5.24% vs 0.73%, P = 0.005), and Arg389Ser49 (36.7% vs 13.6%, P < 0.001) haplotypes of the β₁‐adrenergic receptor, and higher frequency of Gly16Gly (31.5% vs 13.4%, P < 0.001), Glu27Glu genotypes (18.2% vs 10.1%, P = 0.006) and Gly16Gln27Thr164 (15.3% vs 7.4%, P = 0.002), Gly16Glu27Thr164 (13.1% vs 7%, P = 0.004), and Gly16Glu27Ile164 (13.2% vs 6%, P = 0.002) haplotypes of the β₂‐adrenergic receptor compared to control subjects. Conclusion: Our data suggest that common single nucleotide polymorphisms in the β₁ and β₂‐adrenergic receptors are significantly associated with idiopathic ventricular arrhythmias in Turkish population.     

粉防己碱对肝纤维化大鼠氨基酸代谢的影响

目的 观察粉防己碱对肝纤维化大鼠氨基酸代谢的影响。方法 应用四氯化碳制备大鼠肝纤维化模型。24只雄性SD大鼠随机分为正常对照组、病理对照组和粉防己碱治疗组,每组各8只,实验结束时心脏穿刺取血进行血浆氨基酸分析。结果 粉防己碱治疗组的支╱芳比值明显高于病理对照组。结论 粉防己碱具有改善肝纤维化大鼠氨基酸代谢的作用     

Haplotypes of the beta-2 adrenergic receptor associate with high diastolic blood pressure in the Caerphilly prospective study

OBJECTIVES: Current evidence demonstrates that both genetic and environmental factors influence blood pressure. The sympathetic nervous system is a key player in blood pressure control and functional genetic variants of the beta-2 adrenergic receptor (B2AR) have been identified and implicated in the pathogenesis of hypertension. The present study aimed to determine the effects of common haplotypes of the B2AR gene upon blood pressure in the Caerphilly Prospective Study. DESIGN: Two thousand five hundred and twelve men (aged 45-59 years) participated in the study. We selected individuals in the upper (n = 347) and lower (n = 279) quintiles of the diastolic blood pressure distribution fixed at two time points [phase 2 (1984-88) or phase 3 (1989-93)] as cases and controls. METHODS: We analysed two functional polymorphisms (Arg16Gly and Gln27Glu) of B2AR and their haplotypes. RESULTS: We found a higher risk of hypertension in individuals homozygous for the Gln27 compared to those individuals homozygous for Glu27 [odds ratio (OR) = 1.94; 95% confidence interval (CI) = 1.34-2.81; P = 0.001]. Three haplotypes (Gly16Gln27, Gly16Glu27 and Arg16Gln27) were present in both quintile groups. Logistic regression analysis showed that haplotypes with a Gln27 allele (Gly16Gln27 and Arg16Gln27) conferred a significantly higher risk for hypertension than the Gly16Glu27 haplotype (OR = 1.55; 95% CI = 1.11-2.17, OR = 1.37; 95% CI = 1.04-1.81; P = 0.009 and P = 0.027, respectively). However, there was no evidence to support a statistically significant difference in odds ratios for the Gly16Gln27 and Arg16Gln27 haplotypes (P = 0.477), suggesting that it is the Gln27 allele alone, rather than any haplotype, which best explains the association. CONCLUSIONS: In a prospectively studied Caucasian male cohort, high diastolic blood pressure was associated with B2AR haplotypes containing the pro-downregulatory Gln27 variant.