中国北方汉族人群支气管哮喘患者β_2肾上腺素能受体基因多态性研究

目的　探讨中国北方汉族人群 β2 肾上腺素能受体 (β2 AR) 16、2 7和 16 4位点基因多态性与支气管哮喘的相关性。方法　采用等位基因特异性聚合酶链反应 (PCR)方法 ,对 5 8例哮喘缓解期患者进行 β2 AR基因多态性分析检测 ,并与 89名正常者进行对照。结果　 (1)中国北方汉族人群 β2AR基因 16、2 7、16 4位点多态性分布频率与英美高加索人群不同 ;(2 )哮喘组人群β2 AR基因 16位点多态性分布频率显示 ,精氨酸 /精氨酸基因型占 2 4% ,精氨酸 /甘氨酸基因型占 45 % ,甘氨酸 /甘氨酸基因型占 31% ,后者与正常对照组比较 ,比数比 (OR)为 4 0 ,95 %可信限 (CI)为 1 7～ 9 7,差异有显著性(P <0 0 1) ,而等位基因频率与正常对照组比较 ,差异无显著性 (P >0 0 5 )。另外结果还显示 ,β2 AR基因 16位点多态性与哮喘病情严重程度有关联 ,甘氨酸 /甘氨酸基因型在重度哮喘组中所占比与轻度哮喘组和中度哮喘组比较 ,差异有显著性 (P <0 0 5 )。结论　我国北方汉族人群中 β2 AR基因 16位点多态性与支气管哮喘相关联。     

β2肾上腺素受体遗传多态性与血清总IgE关系的研究

人类 β2 肾上腺素受体 (β2 ＡＲ)基因位于染色体 5ｑ31[1,2 ] 。目前已检测出该基因编码区存在着 9个突变位点 (遗传多态性 ) [3 ] ,其中 4个可导致氨基酸序列改变 ,16位点的精氨酸(Ａｒｇ)突变为甘氨酸 (Ｇｌｙ) ,2 7位点的谷胺酰胺 (Ｇｌｎ)突变为谷氨酸 (Ｇｌｕ)的频率较高。国外学者已发现 ,Ｇｌｎ2 7型 β2 ＡＲ与血清总ＩｇＥ增高相关[4 ] 。我们以聚合酶链反应 等位基因特异性寡核苷酸杂交法 (ＰＣＲ ＡＳＯ)对 5 9例哮喘患者的 β2 ＡＲ 16和 2 7位点遗传多态性进行检测 ,并测定其血清总ＩｇＥ ,以探讨我国汉族哮喘人群 β2 ＡＲ…     

山东省汉族人β3肾上腺能受体基因多态性分析

应用多聚酶链反应限制性片段长度多态性（ＰＣＲ－ＲＦＬＰ）技术对２１２例山东省汉族人（非糖尿病６０例，２型糖尿病１３２例）进行β３肾上腺能受体（β３ＡＲ）基因Ｔｒｐ６４Ａｒｇ突变分析。结果表明，山东汉人β３ＡＲ Ｔｒｐ６４Ａｒｇ等位基因变异频率为１６％，２型糖尿病组与非糖尿病组β３ＡＲ Ｔｒｐ６４Ａｒｇ基因型和等位基因分布频率无显著差异（Ｐ〉０．０５）。提示山东省汉族人存在β３ＡＲ基因变异，但这种变     

β_2-肾上腺素能受体基因多态性与新疆维吾尔族患者支气管哮喘间的关系研究

目的 :探讨 β2 肾上腺素能受体 (β2 adrenergicreceptor,β2 AR) 16 ,2 7位点基因多态性与新疆维吾尔族支气管哮喘患者及其临床表型间的关系。方法 :采用序列特异引物聚合酶链反应 (sequencespecificprimers polymerasechainreaction ,SSP PCR)技术检测 12 3例维吾尔族哮喘组患者β2 AR16和 2 7位点基因多态性 ,并与 89例正常组进行对照 ,统计分析 β2 AR16和 2 7位点基因型与哮喘病情严重度的关系。应用UniCAP变应原检测系统 (SWEDENPHARMACIAUniCAPSystems)测定血清嗜酸性粒细胞阳离子蛋白(ECP)、血清总免疫球蛋白E(T IgE)和特异性IgE抗体 (Phadiatop)水平肺功能测定 ,记录 1s用力呼气容量占预计值百分比 (FEU1 % )及最大峰流速 (PEF)。结果 :新疆维吾尔族人群 β2 AR基因 16位点多态性分布以杂合子所占比率较高 ;2 7位点多态性分布以纯合子所占比率较高 ;16 ,2 7位点多态性分布频率与北方汉族人群不同。亦与英、美高加索人群不同。Gly16纯合子基因型的频率在哮喘组明显高于正常对照组的频率 (13 0 1%vs 10 11% ,P <0 0 5 ) ,而且在夜间哮喘组的频率较非夜间哮喘组明显增高 (30 6 %vs 14 9% ,P <0 0 1) ,β2 AR16位点基因多态性在重度哮喘组Gly Gly基因型分布频率明显高于轻度哮喘和中?     

中国人β_2受体遗传多态性与哮喘关系的研究

β2 肾上腺素受体 (β2 ＡＲ)基因与哮喘的关系一直受到广泛的重视。由于不同种族间等位基因的多态性分布不同 ,因此目前尚不能肯定 β2 ＡＲ基因的变异与我国哮喘的发病有何关系。为此我们建立了一种非放射性聚合酶链反应 等位基因特异性寡核苷酸 (ＰＣＲ ＡＳＯ)杂交法 ,从分子水平上对我国汉族人群 β2 ＡＲ 16和 2 7位点的遗传多态性进行了分析 ,并探讨这一多态性和哮喘之间的关系。对象与方法　 5 9例哮喘患者 (哮喘组 )均为居住在南京地区的汉族人 ,男 2 7例 ,女 32例 ,平均年龄 (42± 5 )岁 ,其中轻度 2 6例 ,中度 2 2例 ,重度 11例…     

支气管哮喘β2-肾上腺素受体基因多态性研究

目的探讨β2-肾上腺素能受体(β2-AR)16、27位点基因多态性与支气管哮喘的相关性。方法对2004年7月至2005年9月内蒙古医学院附属医院收治的42例支气管哮喘患者和30名健康者采用等位基因特异性聚合酶链反应(AS-PCR)和两对相对引物PCR法(confronting two-pair primers,PCR-CTPP)进行β2-AR基因多态性分析。结果(1)β2-AR16、27位点基因多态性分布频率与国内某些报道一致,与报道的英美高加索人群不同。(2)哮喘组人群β2-AR基因16位点多态性分布频率显示,精氨酸/精氨酸(Arg/Arg)基因型占14·2%,精氨酸/甘氨酸(Arg/Gly)基因型占80·9%,甘氨酸/甘氨酸(Gly/Gly)基因型占4·0%与健康组比较差异无显著性意义(P>0·05)。等位基因频率与健康组比较差异无显著性意义(P>0·05)。27位点多态性分布频率显示,谷氨酰胺/谷氨酰胺(Gln/Gln)基因型占76·2%,谷氨酰胺/谷氨酸(Gln/Glu)基因型占14·3%,谷氨酸/谷氨酸(Glu/Glu)基因型占9·5%与健康组比较差异无显著性意义(P>0·05)。等位基因频率与健康组比较差异无显著性意义(P>0·05)。结论β2-AR16、27位点基因多态性与哮喘未能证实存在相关性。     

白细胞介素4受体α链基因多态性与支气管哮喘的相关性研究

目的 检测白细胞介素4受体α链（IL-4Rα）基因Ile50Val位点的多态性在汉族人群中的分布频率，探讨Ile50Val位点多态性与支气管哮喘（简称哮喘）的相关性。方法 对2002至2004年间暨南大学附属第一医院呼吸科门诊及住院患者和体检者，利用扩增阻滞突变系统-聚合酶链反应（ARMS-PCR）对103例哮喘患者（哮喘组）的IL-4Rα链基因的Ile50Val位点多态性进行检测，并与62名健康人（对照组）进行对照。结果 Ile50Val位点在汉族人群中存在3种（Ile50／Ile50、Ile50／Val50、Val50／Val50）基因型，103例哮喘组的分布频率分别为32．0％（33／103）、35．0％（36／103）、33．0％（34／103）；62名对照组的分布频率分别为29．0％（18／62）、37．1％（23／62）、33．9％（21／62）；各基因型分布频率哮喘组与对照组比较差异无统计学意义（χ^2=0．172，P〉0．05）。哮喘组与对照组的Ile50、Val50等位基因频率分别为49．5％、47．6％、50．5％和52．4％；哮喘组与对照组Ile50及Val50等位基因频率比较差异无统计学意义（χ^2=0．116，P〉0．05）。结论 IL-4Rα链基因Ile50Val位点在汉族人群中存在多态性（Ile50／Ile50、Ile50／Val50、Val50／Val50）；Ile50Val位点的多态性与哮喘不存在相关性。     

胰岛素抵抗的分子遗传学病因

目的探讨中国人群胰岛素受体底物１（ＩＲＳ１）基因、β３肾上腺素受体（β３ＡＲ）基因突变与胰岛素抵抗的关系。方法对２８１例病人通过糖耐量试验分为糖耐量正常组、糖耐量低减组及糖尿病组，分别对之进行ＩＲＳ１基因、β３ＡＲ基因多态性分析。结果糖尿病者和糖耐量正常者相比，ＩＲＳ１基因、β３ＡＲ基因的基因型频率及等位基因频率存在明显差异；多元回归分析发现：胰岛素水平和ＩＲＳ１基因、β３ＡＲ基因多态性显著相关。非条件多因素Ｌｏｇｉｓｔｉｃ回归模型发现：糖尿病和β３ＡＲ基因多态性有明显关系。结论β３ＡＲ基因突变可能是与胰岛素抵抗有关疾病的共有危险因素。     

ADAM33基因Met764Thr位点多态性与支气管哮喘发病及患者肺功能的相关性

目的探讨中国华南地区汉族人群ADAM33基因Met764Thr位点多态性与支气管哮喘（简称哮喘）及其患者肺功能的相关性。方法对164例中国华南汉族哮喘患者（哮喘组）及112名汉族健康者（健康对照组），应用聚合酶链反应和限制性片段长度多态性（PCR-RFLP）、DNA测序及肺功能测定的方法。结果（1）不同种族人群ADAM33基因Met764Thr位点等位基因频率的比较差异无统计学意义（χ^2=6．77，P〉0．05）；（2）ADAM33基因Met764Thr位点3种基因型（Met764／Met764、Met764／Thr764、Thr764／Thr764）在哮喘组分布频率分别为78．7％（129／164）、18．3％（30／164）、3．0％（5／164）；健康对照组分布频率分别为91．1％（102／112）、6．3％（7／112）、2．7％（3／112）；各基因型分布频率哮喘组与健康对照组比较差异有统计学意义（χ^2=8．46，P〈0．05）。ADAM33基因Met764Thr位点，Thr764等位基因在哮喘组与健康对照组分布频率分别为0．122、0．058，哮喘组与健康对照组Met764及，Thr764等位基因频率比较差异有统计学意义（χ^2=6．27，P〈0．05）；（3）单变量Logistic回归分析Met764Thr位点基因多态性与哮喘的关系表明，相对Met764／Met764基因型而言，Met764／Thr764杂合型与Met764／Thr764＋Thr764／Thr764基因型均能显著增加哮喘发生的危险性[OR值及95％可信区间（CI）分别为3．389（1．430～8．030）、2．767（1．308～5．854），P均〈0．05]；（4）在哮喘组中3种基因型的用力肺活量（FVC）实测值／预测值％、第一秒用力呼气容积（FEV1）实测值／预测值％水平比较差异有统计学意义（F值分别为0．49、5．17，P均〈0．05）。结论ADAM33基因Met764Thr位点基因多态性与中国华南汉族人群哮喘发病及患者的肺功能相关。     

缺血性脑卒中患者肿瘤坏死因子基因βThr26Asn多态性分析

目的：探讨肿瘤坏死因子（ＴＮＦ）β基因ＴＮＦβＴｈｒ２６Ａｓｎ多态性与中国人缺血性脑卒中之间的关系。方法：利用ＰＣＲ技术和分子杂效技术对北京地区１０１例缺血性脑卒中患患者及１０１例对照进行肿瘤坏死因子基因ＴＮＦβＴｈｒ２６Ａｓｎ多态性的检测和分析。结果：缺血性脑卒中患者ＴＮＦβＴｈｒ２６Ａｓｎ多态性位点基因型频率及等位基因频率在两组中分布无显著性差异。结论：ＴＮＦβ基因Ｔｈｒ２６Ａｓｎ多态性可能不     

Polymorphisms in beta-adrenergic receptor genes in the acquired long QT syndrome

INTRODUCTION: Sympathetic activation is a trigger for life-threatening arrhythmias in many patients with the congenital long QT syndrome (LQTS), and an increase in heart rate has been reported just prior to torsades de pointes in patients with drug-associated (acquired) LQTS (aLQTS). We compared the frequencies of five recognized nonsynonymous coding region polymorphisms in genes encoding the beta1-adrenergic and beta2-adrenergic receptors (AR) in 93 patients with aLQTS and 3 control groups: an ethically diverse set of individuals from middle Tennessee (n = 71), a subset of the Polymorphism Discovery Resource obtained from National Human Genome Research Institute (n = 89), and patients who tolerated QT-prolonging drugs without aLQTS (non-aLQTS group; n = 66). METHODS AND RESULTS: Polymerase chain reaction-restriction fragment length polymorphism was used to screen for Ser49Gly and Gly389Arg (beta1-AR) and Thr164Ile (beta2-AR). For Arg16Gly and Gln27Glu, polymorphic sites 33 nucleotides apart in the beta2-AR, single-stranded conformational polymorphism was used to distinguish among the 4 possible haplotypes and 10 possible genotypes. Allele frequencies were similar among the 4 groups at the 2 beta1-AR sites. The uncommon Ile164 variant in beta2-AR was slightly more frequent in patients (3.2%) than in any of the 3 control groups (0.6% to 2.3%). At the 16-27 neighboring sites in the beta2-AR, one haplotype (Arg16/Glu27) was not detected, as in previous studies; hence, only 6 genotypes were present. There were fewer Gly16/Gln27 homozygotes in the non-aLQTS group (1.5%) than in two other control groups or the aLQTS group (8.5% to 10%). CONCLUSION: None of the five common nonsynonymous coding region polymorphisms in the beta-AR genes predict drug-associated torsades de pointes, although the Gly16/Gln27 haplotype may be a risk factor.     

Association between beta2-adrenergic receptor genetic polymorphisms and nocturnal asthmatic patients of Chinese Han nationality

BACKGROUND: As a result of the finding that the mutation of Arg into Gly at beta(2)-adrenergic receptor (beta(2)-AR)16 loci could promote the downregulation effect triggered by the beta(2)-agonist, it was supposed that Gly16 might be associated with the downregulation of beta(2)-AR in patients with nocturnal asthma. OBJECTIVE: It was the aim of this study to analyze the association between beta(2)-AR genetic polymorphisms and nocturnal asthmatic patients of Chinese Han nationality. METHODS: A polymerase chain reaction allele-specific oligonucleotide hybridization assay was used to determine 16 and 27 loci alleles of beta(2)-AR genetic polymorphisms in 25 nocturnal asthmatic patients (nocturnal asthma group), 22 non-nocturnal asthmatic patients (non-nocturnal asthma group), and 72 healthy people (control group). All people investigated were of Chinese Han nationality. RESULTS: The distribution frequency of genotype Arg/Arg, Arg/Gly, and Gly/Gly at beta(2)-AR 16 loci was 12, 16 and 72% in the nocturnal asthma group; and 27, 41 and 32% in the non-nocturnal asthma group. There was a significant increase in the frequency of genotype Gly/Gly and allele Gly in the nocturnal asthma group compared with the non-nocturnal asthma group (p < 0.01). However, there was no significant difference in the frequency of genotype Gly/Gly and allele Gly in the non-nocturnal asthma group, compared with the control group. There was no significance in the frequency of the genotypes and alleles of beta(2)-AR 27 loci among the three groups (p > 0.05). CONCLUSION: The Gly16 polymorphism of beta(2)-AR was overrepresented in nocturnal asthmatic patients, correlated with nocturnal asthma, and therefore appeared to be an important genetic factor in the expression of this asthmatic phenotype.     

Beta2 adrenoceptor functional gene variants,obesity, and blood pressure level interactions in the general population

We investigated the association of beta2 adrenoceptor functional gene variants (Arg16Gly, Gln27Glu, and Thr164Ile polymorphisms), obesity phenotypes, and blood pressure levels in a large, ethnically mixed urban population. The individuals (n=1576) were randomly selected for a cross-sectional study of cardiovascular risk factors in Vitória, Brazil. Statistically significant associations among systolic blood pressure and the Arg16Gly and Thr164Ile variants were identified in univariate analysis. The Gly16/Gly16 genotype was still associated with systolic blood pressure (SBP) in multivariate analysis adjusting for age, gender, ethnicity, total cholesterol, diabetes, and body mass index (BMI) (P=0.01). The Arg16 allele was the only genotypic variable associated with BMI, and, in a dominant model, it remained associated with an increased BMI even after adjustment for age, gender, ethnicity, triglycerides, HDL cholesterol, LDL cholesterol, diabetes, and hypertension status (P=0.02). Although the different polymorphisms did not interact in the determination of SBP, a significant interaction with BMI (P=0.02), not through linkage disequilibrium, was identified between the Gln27Glu and the Thr164Ile variants. Furthermore, a significant interaction among the Arg16Gly polymorphism and BMI (P=0.036) and waist-hip ratio (P=0.003) in determining SBP was disclosed by ANOVA factorial modeling, with SBP used as the dependent variable. An interaction between the Thr164Ile polymorphism and waist-hip ratio was also identified (P=0.018). Finally, multiple logistic regression models showed a 1.48-fold increase in the risk of hypertension in individuals harboring the Gly16/Gly16 genotype and a 1.31-fold (P=0.01) and a 1.49-fold (P=0.003) increased risk of obesity in individuals harboring the Gln27/Gln27 genotype or the presence of the Arg16 allele, respectively. Taken together, these data provide evidence for a strong but complex relation between beta-adrenoceptor gene variants, hypertension, and obesity.     

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.     

Polymorphisms of the beta(2)-adrenergic receptor determine exercise capacity in patients with heart failure

The beta(2)-adrenergic receptor (beta(2)AR) exists in multiple polymorphic forms with different characteristics. Their relevance to heart failure (HF) physiology is unknown. Cardiopulmonary exercise testing was performed on 232 compensated HF patients with a defined beta(2)AR genotype. Patients with the uncommon Ile164 polymorphism had a lower peak VO(2) (15.0+/-0.9 mL. kg(-1). min(-1)) than did patients with Thr164 (17.9+/-0.9 mL. kg(-1). min(-1), P<0.0001). The percentage achieved of predicted peak VO(2) was also lower in patients with Ile164 (62. 3+/-4.5% versus 71.5+/-5.1%, P=0.045). The relative risk of a patient having a VO(2) 相似文献   

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.     

Association between beta2-adrenergic receptor genetic polymorphisms and total serum IgE in asthmatic patients of Chinese Han nationality

BACKGROUND: beta(2)-Adrenergic receptor (beta(2)-AR) polymorphisms occurring at amino acid position 16 (Arg-Gly) and 27 (Gln-Glu) are known to be functionally relevant and also disease-modifying in subjects with asthma. It has been found in Caucasoid asthmatic patients that the Gln27 genotype beta(2)-AR was associated with an increase in total serum IgE levels. The association between beta(2)-AR genetic polymorphisms and total serum IgE in asthmatic patients of Chinese Han nationality remains to be established. OBJECTIVES: It was the aim of this study to investigate the association between beta(2)-AR genetic polymorphisms and total serum IgE in asthmatic patients of Chinese Han nationality. METHODS: All 59 asthmatic patients investigated (27 males and 32 females, aged between 16 and 60 years) were people of Chinese Han nationality. They were tested for their total serum IgE levels with the enzyme-linked immunosorbent assay test, and beta(2)-AR genetic polymorphisms were tested with the polymerase chain reaction allele-specific oligonucleotide hybridization assay. RESULTS: There was a significant difference of serum IgE levels among three beta(2)-AR 27 loci groups (p < 0.0001), with the highest IgE level [(1.24 +/- 0.25) x 10(6) IU/l] in the Gln/Gln group and the lowest IgE level [(0.48 +/- 0.06) x 10(6) IU/l] in the Glu/Glu group. No polymorphism of beta(2)-AR 16 loci was found to be associated with total serum IgE (p > 0.05). CONCLUSIONS: Our research suggested that in asthmatic patients of Chinese Han nationality, the beta(2)-AR genetic polymorphism at 27 loci could be associated with serum IgE levels and it might therefore play an important role in the determination of phenotypes of bronchial asthma.     

Is there a role of the Thr164Ile-β2-adrenoceptor polymorphism for the outcome of chronic heart failure?

OBJECTIVE: The Thr164Ile-beta(2)-adrenoceptor (AR) polymorphism exhibits lower affinities for catecholamines and reduced basal and agonist-stimulated adenylyl cyclase activity in vitro. It has been suggested that patients with chronic heart failure (CHF) due to ischemic or dilated cardiomyopathy carrying the Thr164Ile-beta(2)AR polymorphism exhibit much more rapid progression to death or heart transplantation (HTX) than CHF-patients carrying the homozygous Thr164-beta(2)AR. This study aimed to further evaluate the role of the Thr164Ile-beta(2)AR in CHF. For this we hypothesized that the Thr164Ile-beta(2)AR variant should be more abundant in HTX-patients than in patients with stable CHF or healthy controls. METHODS AND RESULTS: We genotyped 309 HTX-patients, 520 stable CHF-patients and 328 healthy controls for the three beta(2)AR variants Arg16Gly, Gln27Glu and Thr164Ile. The prevalence of the Thr164Ile-beta(2)AR variant was not considerably different in HTX-patients (2.3%) from that in CHF-patients (1.9%) or healthy controls (2.1%). Similarly, the frequency of the minor Ile164-allele was f(-)=0.0106 in HTX-patients, f(-)=0.0096 in CHF-patients and f(-)=0.0113 in healthy controls. CONCLUSIONS: The prevalence of the hypofunctional Thr164Ile-beta(2)AR variant and the frequency of the Ile164-allele were almost identical in CHF-patients, who had undergone HTX, with those in patients with stable CHF or in healthy controls. Thus, the role of the Thr164Ile-beta(2)AR in CHF remains questionable.     

Variants of the ADRB2 Gene in COPD: Systematic Review and Meta-Analyses of Disease Risk and Treatment Response

The β₂-adrenergic receptor (ADRB₂) is an important regulator of airway smooth muscle tone in chronic obstructive pulmonary disease (COPD). Variants that impair ADRB₂ function could increase disease risk or reduce the response to endogenous and inhaled adrenergic agonists in COPD. We performed a systematic review and three meta-analyses to assess whether three functional variants (Thr164Ile, Arg16Gly, and Gln27Glu) in the ADRB₂ gene are associated with elevated risk of disease or reduced therapeutic response to inhaled β₂-agonists in COPD. We searched the medical literature from 1966 to 2017 and found 16 relevant studies comprising 85381 study subjects. The meta-analyses found no significant association between ADRB₂ genotype and COPD risk. The summary odds ratios (ORs) for COPD in Thr164Ile homozygotes and heterozygotes were 2.57 (95% confidence interval (CI): 0.54–12.4) and 1.17 (95% CI: 0.96–1.44), respectively. Corresponding summary ORs for COPD in Arg16Gly homozygotes and heterozygotes were 0.97 (95% CI: 0.76–1.22) and 1.01 (95% CI: 0.81–1.26), while summary ORs for COPD in Gln27Glu homozygotes and heterozygotes were 1.00 (95% CI: 0.80–1.25) and 0.94 (95% CI: 0.69–1.24), respectively. When stratified by ethnicity, the summary ORs for COPD did not differ from 1.0 for any of the ADRB₂ variants among Asian, Caucasian, or African populations. We found no consistent associations between ADRB₂ genotype and treatment response to inhaled β₂-agonists in COPD. This systematic review and meta-analyses found that COPD risk and response to inhaled β₂-agonists were not associated with Thr164Ile, Arg16Gly, and Gln27Glu genotypes. However, identified cases of Thr164Ile were few, and additional studies of rare ADRB₂ genotypes are required.     

Variants in the human beta 1-, beta 2-, and beta 3-adrenergic receptor genes are not associated with morbid obesity in children and adolescents

AIM: beta-adrenergic receptors (beta-ARs) are of key importance for the regulation of lipolysis and thermogenesis by catecholamines. Genetic defects in expression or function of beta(1)- beta(2)- and/or beta(3)-AR could affect energy homeostasis and predispose an individual towards the development of obesity. We therefore investigated the possible association of polymorphisms in the beta-adrenergic receptor genes with early onset obesity. METHODS: Frequencies of the following variants were assessed in extremely obese children and healthy underweight controls: Gly/Ser in codon 49 and Arg/Gly in codon 389 of the beta(1)-AR, Arg/Gly in codon 16 and Gln/Glu in codon 27 of the beta(2)-AR, Trp/Arg in codon 64 of the beta(3)-AR. RESULTS: The Ser49 allele in the beta(1)-AR gene was found at a frequency of 0.131 in obese and 0.136 in lean subjects (p = 0.835), while the Gly389 allele in the beta(1)-AR had a frequency of 0.319 in obese and 0.328 in lean subjects (p = 0.802). Gly16 in the beta(2)-AR was found with a frequency of 0.590 in obese and 0.611 in lean subjects (p = 0.591) and the Glu27 allele in the beta(2)-AR had a frequency of 0.380 in obese and 0.420 in lean subjects (p = 0.298). CONCLUSION: We did not detect significant differences for allele and carrier frequencies of individual polymorphisms. Together with previously obtained data on genotype distribution of a beta(3)-AR variant in the same study group, no significant differences were found between obese and lean subjects for the distribution of individuals with variants in none, one, two or all three beta-ARs. Our data make it unlikely that polymorphisms in beta-ARs are involved in the pathogenesis of early onset obesity.