β肾上腺素能受体基因家族在中国东北高血压病高发人群中的基因型分析

目的　检测高血压病高发地区人群中 β肾上腺素能受体 (β- adrenergic receptor,β- AR)基因家族β1 亚型 (β1 - AR) Arg389Gly,β2 亚型 (β2 - AR) Arg16 Gly和β3亚型 (β3- AR) Trp6 4 Arg位点的等位基因频率和基因型频率 ,分析 β- AR基因在高血压病发生、发展中的作用。方法　应用聚合酶链反应和限制性片段长度多态性技术检测 14 4例高血压病患者和 174名正常人的基因型 ,同时测定相关的生化指标 ,并进行病例 -对照统计学分析。结果　 β1 - AR Arg389Gly位点的 Gly/ Gly基因型频率在高血压病组与正常对照组差异有显著性 ,β2 - AR Arg16 Gly位点和 β3- AR Trp6 4 Arg位点的基因型频率在两组间差异无显著性。结论　 β1 - AR Arg389Gly多态与高血压病的发病具有相关性。     

应用温度梯度凝胶电泳筛选冠心病人β2-AR的Gln27Glu突变

目的 :β2 肾上腺受体 (β2 AR)基因的多态型与高血压等疾病具有相关性。现已发现 β2 AR基因在欧美人群中存在 3种突变(Arg16Gly、Gln2 7Glu、Ser16 4Phe) ,这 3种突变是否与冠心病的发生发展存在相关性还不清楚。为研究中国人 β2 -AR基因多态性与冠心病发生的关系 ,先行建立检测 β2 -AR(Gln2 7Glu)突变的温度梯度凝胶电泳 (TGGE)技术 ,并以此检测冠心病人 β2 AR基因的多态型。方法 :1.引物 :根据已知人 β2 -AR基因序列 ,设计合成 1对引物 ,Sence :5’ -GAAGCCATGCGCCGGACC - 3’ ,Antisence:5’ -AGTAGTTGGTGA…     

广东汉族人β2-肾上腺素能受体基因Gln27Glu多态性

目的 探讨β2-AR 16位点基因多态性在广东汉族人群中的分布．方法 应用聚合酶链反应技术对122例正常人β2-肾上腺素能受体基因Gln27Glu进行扩增并进行图谱分析．并结合文献进行了不同种族间的分析比较．结果 广东汉族人群β2-AR基因27位点多态性分布频率：Gln／Gln基因型占36．88％，Gln／Glu基因型占52．46％，Glu／Glu基因型占10．66％．结论 广东汉族人群存在出β2-AR Gln27Glu基因多态性，其分布频率与英美高加索人群有一定差异．     

广东汉族人β2-肾上腺素能受体基因Gln27Glu多态性

目的探讨β2-AR 16位点基因多态性在广东汉族人群中的分布.方法应用聚合酶链反应技术对122例正常人β2-肾上腺素能受体基因Gln27Glu进行扩增并进行图谱分析.并结合文献进行了不同种族间的分析比较.结果广东汉族人群β2-AR基因27位点多态性分布频率:Gln/Gln基因型占36.88%,Gln/Glu基因型占52.46%,Glu/Glu基因型占10.66%.结论广东汉族人群存在出β2-AR Gln27Glu基因多态性,其分布频率与英美高加索人群有一定差异.     

β3肾上腺素能受体基因多态性与新疆哈萨克族人群高血压病的相关研究

目的 检测新疆哈萨克族人群中β3肾上腺素能受体(β3-adrenergic receptor,β3-AR)Trp64Arg位点的等位基因频率和基因型频率,分析β3-AR基因在高血压病发生、发展中的作用.方法 应用聚合酶链反应和限制性片段长度多态性技术检测189例高血压病、197例血压正常高值和135例正常人的基因型,同时测定相关的生化指标,并进行病例-对照统计学分析.结果 β3-ARTrp64Arg位点的基因型频率在3组间无统计学差异.结论 β3-AR Trp64Arg多态性与哈萨克族高血压病的发生无明显关联.     

β3肾上腺素能受体基因多态与新疆 哈萨克族人群高血压病的相关研究

目的：检测新疆哈萨克族人群中β3肾上腺素能受体Trp64Arg位点的等位基因频率和基因型频率，分析β3-AR基因在高血压病发生、发展中的作用。方法：应用聚合酶链反应和限制性片段长度多态性技术检测189例高血压病、197例血压正常高值和135例正常人的基因型，同时检测相关的生化指标，并进行病例-对照统计学分析。结果：β3-AR Trp64Arg位点的基因型频率在3组间无统计学差异。结论：β3-AR Trp64Arg多态性与哈萨克族高血压病的发生无明显关联。     

PPAR-γ2基因和β3-AR基因联合变异与新疆哈萨克族人群高血压病的关系

目的检测新疆哈萨克族人群中β3肾上腺素能受体(β3-adrenergic receptor,β3-AR)基因Trp64Arg多态和(peroxisome proliferators-activated receptor gamme2,PPARγ2) Pro12Ala多态联合变异与高血压病的关系。方法应用聚合酶链反应和限制性片断长度多态性技术检测247例高血压病、224例血压正常高值和143例正常人的基因型,同时测定相关的生化指标,并进行病例-对照统计学分析。结果β3-AR基因Trp64Arg多态、PPARγ2基因Pro12Ala多态及两基因的联合变异的基因型和等位基因频率在三组间无统计学差异。结论β3-AR Trp64Arg多态、PPARγ2Pro12Ala多态及两基因的联合变异与哈萨克族高血压病的发生无明显关联。     

ERCC2/XPD和XRCC1基因多态性与鼻咽癌放化疗患者临床转归的相关性研究

目的探讨D组着色性干皮病偶联因子(XPD)的核苷酸切除修复交叉互补基因2(ERCC2/XPD) Lys751Gln和XRCC1 Arg194Trp基因多态性与鼻咽癌(NPC)患者放化疗敏感性及预后相关性。方法选择2015年1月至2016年12月在海南医学院第一附属医院首次接受治疗的NPC患者128例,其中男性82例,女性46例;年龄35～77岁,平均年龄56.28岁。根据放化疗是否敏感分为敏感组和不敏感组。记录所有患者临床资料。采用聚合酶链反应(PCR)检测2组患者ERCC2/XPD Lys751Gln和XRCC1 Arg194Trp基因多态性,采用Hardy-Weinberg遗传平衡吻合度检验法计算各基因型的理论值。Logistic回归分析影响NPC放化疗敏感性的因素,Kaplan-Meier分析不同基因型组间总生存期(OS)的差异。结果敏感组72例,不敏感组56例。敏感组与不敏感组性别、年龄、吸烟习惯、Karnofsky(KPS)评分、化疗方式、T分期比较,差异无统计学意义(P 0.05),两组患者N分期、美国癌症联合委员会(AJCC)分期、分化程度、淋巴结转移比例、放疗前肿瘤靶区体积(GTVnx)及淋巴结靶区体积(GTVnd)差异有统计学意义(P 0.05);两组间ERCC2/XPD Lys751Gln和XRCC1 Arg194Trp的3种基因型均符合Hardy-Weinberg遗传平衡定律(P 0.05);两组患者ERCC2/XPD Lys751Gln基因和XRCC1 Arg194Trp基因的不同基因型分布比较,差异有统计学意义(P 0.05);多因素Logistic回归分析显示,N分期N2+N3期、放疗前GTVnx、放疗前GTVnd、淋巴结转移及ERCC2/XPD Lys751Gln的携带Gln基因型和XRCC1Arg194Trp的携带Trp基因型是影响NPC患者放化疗的独立危险因素;携带ERCC2/XPD Lys751Gln基因Gln等位基因患者3年OS为60.00%,不携带Gln等位基因患者3年OS为79.17%,两者差异具有统计学意义(P 0.05);携带XRCC1 Arg194Trp基因Trp等位基因患者3年OS为58.14%,不携带Trp等位基因患者3年OS为73.81%,两者差异具有统计学意义(P 0.05)。结论 ERCC2/XPD Lys751Gln和XRCC1 Arg194Trp基因多态性与NPC患者放化疗敏感性有关,分别携带Gln、Trp等位基因是放化疗敏感性的危险因素,且患者OS明显降低。     

DRD3基因Ser9Gly多态性与不同性别精神分裂症患者工作记忆的关联研究

目的:探讨DRD3基因Ser9Gly多态性与汉族人群不同性别精神分裂症患者工作记忆的关联.方法:选取符合美国精神障碍诊断与统计手册第4版(DSM-Ⅳ)中精神分裂症的诊断标准的汉族患者526例和415例汉族健康对照,检测DRD3基因Ser9Gly多态性,用中国修订韦氏成人智力量表(WAIS-RC)进行智商(IQ)评定,N-back任务测量工作记忆能力.采用协方差分析等方法分析DRD3基因Ser9Gly多态性与精神分裂症工作记忆的关联.结果:在全体被试中,男性的1-back[(0.50±0.27) vs.(0.56±0.25)]和2-back[(0.25±0.22) vs.(0.28±0.22)]任务错误率小于女性(均P＜0.05).男性患者中,Ser/Ser基因型的1-back任务错误率[(0.39±0.23) vs.(0.33±0.23)]高于Gly/Ser基因型,IQ[(97.4±15.1) vs.(101.9±13.4)]低于Gly/Ser基因型(均P＜0.05);男性对照组中,不同基因型之间工作记忆及IQ得分差异无统计学意义(均P＞0.05).女性被试中,Ser9Gly多态性不同基因型的工作记忆与IQ得分差异无统计学意义(均P＞0.05).结论:精神分裂症患者的工作记忆可能存在性别差异,Ser9Gly多态性在汉族人群中与精神分裂症的工作记忆障碍有一定相关性.     

IL-4R、IL-13、ADAM33基因多态性与中国皖南地区汉族人群支气管哮喘的相关性研究

目的:探讨IL-4受体基因Arg551Gln(rs1801275)、IL-13基因Arg130Gln(rs20541)、ADAM33基因T1(rs2280091)位点基因多态性与中国皖南地区汉族人群支气管哮喘的相关性。方法:采用病例-对照的方法,用聚合酶链反应及直接基因测序法比较116例支气管哮喘组与70例正常人对照组之间基因型、等位基因频率的差异。结果:哮喘组和对照组IL-4受体基因Arg551Gln位点和IL-13基因Arg130Gln位点的基因型和等位基因型频率的差异有统计学意义,ADAM33基因T1位点基因型哮喘组和对照组差异有统计学意义,等位基因型频率在哮喘组和对照组差异无统计学意义。结论:提示IL-4R Arg551Gln(rs1801275)位和IL-13基因Arg130Gln(rs20541)位的多态性可能与中国皖南地区汉族哮喘有相关性;ADAM33基因(rs2280091)T1位点位的多态性可能与中国皖南地区汉族哮喘无相关性。     

Association of beta2 adrenergic receptor polymorphisms and related haplotypes with triglyceride and LDL-cholesterol levels

Adrenergic receptors regulate lipid mobilization, energy expenditure and glycogen breakdown. The beta(2) adrenergic receptor (beta(2)-AR) gene may constitute a potential candidate gene to explain part of the genetic predisposition to human obesity and correlated traits. With regard to the association between beta(2)-AR gene polymorphisms and obesity-related metabolic disorders, published reports give conflicting results. We investigated the role of three polymorphisms, and related haplotypes of the beta(2)-AR in the obesity and related traits in a cohort of overweight/obese subjects. We characterized one single nucleotide polymorphism (SNP) in the promoter region (5'LC-Cys19Arg) and two in the coding region (Gly16Arg and Gln27Glu) of the beta(2)-AR in 642 consecutively recruited overweight/obese subjects in whom extensive clinical and biochemical analysis was performed. The effect of the polymorphisms on quantitative variables was investigated using multiple linear regression analysis. 5'LC-Cys19 homozygous showed higher triglyceride and LDL-cholesterol levels compared to 5'LC-Arg19 homozygous (P=0.03 and P=0.01, respectively). Similar increase in triglyceride and LDL-cholesterol levels was observed for Arg/Arg genotype compared to Gly/Gly genotype of Gly16Arg polymorphism (P=0.02 and P=0.01, respectively) and for Gln/Gln genotype compared to Glu/Glu genotype of the Gln27Glu polymorphism (P=0.01 and P=0.03, respectively). The 5'LC-Cys(19)Arg(16)Gln(27) haplotype determined a significant increase in triglyceride and LDL-cholesterol levels compared to 5'LC-Arg(19)Gly(16)Glu(27) haplotype (P=0.05 and P=0.02, respectively). Our findings provide additional weight to previous observations on the influence of these three genetic variants on lipid phenotypes; particularly on the increase of triglycerides and LDL-cholesterol levels in overweight/obese subjects carrying the 5'LC-Cys(19)Arg(16)Gln(27) haplotype.     

Beta1-adrenergic receptor gene polymorphisms in Mexican patients with idiopathic dilated cardiomyopathy

The objective of the study was to evaluate the role of beta1-adrenergic receptor gene polymorphisms (Ser49Gly and Arg389Gly) as susceptibility markers for idiopathic dilated cardiomyopathy (IDC) in Mexican patients. The polymorphisms were analyzed in 47 patients with IDC and 93 ethnically matched healthy controls by polymerase chain reaction-restriction fragment length polymorphism. The Ser49Gly allele and genotype frequencies were similar in patients and healthy controls. On the other hand, the analysis of the Arg389Gly polymorphism showed an increased frequencies of the *Gly allele (pC = 0.022, OR = 2.16) and *Arg/*Gly genotype (pC = 0.027, OR = 2.70) in the group of IDC patients when compared to healthy controls. The data suggest that Arg389Gly polymorphism could be involved in the genetic susceptibility to develop IDC in Mexicans.     

Beta‐adrenergic receptor gene polymorphisms and cardiovascular reactivity to stress in Black adolescents and young adults

Cardiovascular reactivity to stress and β‐adrenergic receptor (β‐AR) function may contribute to the development of hypertension. As Black Americans have an increased risk of hypertension, we evaluated associations between β₁‐AR (Arg389Gly) and β₂‐AR (Arg16Gly, Gln27Glu) gene variants and cardiovascular reactivity in 500 Black youth. Heart rate, preejection period, total peripheral resistance, and blood pressure reactivity were measured during cold and psychological stress. The Arg389Gly polymorphism in the β₁‐AR was associated with preejection period reactivity in males but not in females. The Arg16Gly polymorphism in the β₂‐AR was associated with diastolic blood pressure reactivity only during video game stress. An association between the Gln27Glu polymorphism in the β₂‐AR and vascular reactivity depended on sex. Thus, specific patterns of associations emerged between genetic variations in β‐ARs and cardiovascular reactivity in young Blacks.     

Association of molecular variants of luteinizing hormone with male infertility

Luteinizing hormone (LH) stimulates the interstitial Leydig cells to produce testosterone, which is essential for spermatogenesis. Abnormalities in the function of LH may affect the process of spermatogenesis and thus result in infertility. The aim of this study was to determine the association of three known variants of LH (Gln54Arg [Trp8Arg; Ile15Thr] and Gly102Ser) with male infertility. A total of 145 infertile men and 200 healthy fertile men were recruited and screened for the presence of these three LH variants. The Gln54Arg variant could not be detected in either of the groups studied. Twelve infertile (8.2%) and 15 fertile (7.5%) men were found to carry the [Trp8Ile; I15Thr] variant, but its occurrence did not show any significant difference between the patient and control groups. The Gly102Ser variant was detected in five patients with infertility (3.4%), but not in the control subjects (P = 0.013). This study showed that the Gln54Arg and [Trp8Ile; I15Thr] variants in the LHbeta gene were not associated with male infertility, whereas the Gly102Ser variant might be implicated in infertility in some Singapore Chinese men.     

Association of β2-adrenergic receptor polymorphisms with severe asthma

BACKGROUND: There is considerable interest in the role of different candidate loci in the development of asthma. This study investigates the association between asthma severity and previously identified polymorphisms at two sites within the beta2-adrenergic receptor (beta2AR) gene: the Arg16-->Gly16 and Gln27-->Glu27 alleles. METHODS: Restriction enzyme analysis of amplified beta2AR gene products (PCR-RFLP) was used to analyse the frequency of the Arg16-->Gly16 and Gln27-->Glu27 polymorphisms within the beta2AR gene in 95 severe asthmatic patients (with a markedly increased risk of death from asthma), 59 mild asthmatic patients, and a control group of 92 nonasthmatic subjects. RESULTS: The Gly16 polymorphism was significantly associated with asthma severity with odds ratios (95% CI) for the Gly16 allele being 1.56 (1.02-2.40, P = 0.04) and 0. 98 (0.61-1.57, P = 0.92) for the severe and mild asthma groups, respectively. The corresponding odds ratios (95% CI) for Gly16 homozygotes were 1.91 (0.82-4.41, P = 0.13) and 0.82 (0.35-1.92, P = 0.65) for the severe and mild asthma groups, respectively. There was no significant association between either polymorphism at amino acid 27 and asthma or asthma severity. CONCLUSIONS: We conclude that the polymorphisms of amino acids 16 and 27 of the beta2AR gene are not associated with the development of asthma per se, but that the Gly16 polymorphism may play a role in the pathogenesis of asthma severity.     

Clinical spectrum and molecular basis of recessive congenital methemoglobinemia in India

We report the clinical features and molecular characterization of 23 patients with cyanosis due to NADH‐cytochrome b5 reductase (NADH‐CYB5R) deficiency from India. The patients with type I recessive congenital methemoglobinemia (RCM) presented with mild to severe cyanosis only whereas patients with type II RCM had cyanosis associated with severe neurological impairment. Thirteen mutations were identified which included 11 missense mutations causing single amino acid changes (p.Arg49Trp, p.Arg58Gln, p.Pro145Ser, p.Gly155Glu, p.Arg160Pro, p.Met177Ile, p.Met177Val, p.Ile178Thr, p.Ala179Thr, p.Thr238Met, and p.Val253Met), one stop codon mutation (p.Trp236X) and one splice‐site mutation (p.Gly76Ser). Seven of these mutations (p.Arg50Trp, p.Gly155Glu, p.Arg160Pro, p.Met177Ile, p.Met177Val, p.Ile178Thr, and p.Thr238Met) were novel. Two mutations (p.Gly76Ser and p.Trp236X) were identified for the first time in the homozygous state globally causing type II RCM. We used the three‐dimensional (3D) structure of human erythrocyte NADH‐CYB5R to evaluate the protein structural context of the affected residues. Our data provides a rationale for the observed enzyme deficiency and contributes to a better understanding of the genotype–phenotype correlation in NADH‐CYB5R deficiency.     

Toll-like receptor (TLR) 2 and 4 mutations in periodontal disease

Toll-like receptors (TLR) are signal molecules essential for the cellular response to bacterial cell wall components. Different functional effective polymorphisms for the TLR 4 gene (Asp299Gly; Thr399Ile) and for the TLR 2 gene (Arg677Trp, Arg753Gln) have recently been described that are associated with impaired lipopolysaccharide signal transduction. A total of 122 patients with chronic periodontal disease and 122 healthy unrelated controls were genotyped for the Asp299Gly and Thr399Ile polymorphism of the TLR 4 gene and the Arg677Trp and Arg753Gln mutation of the TLR 2 gene. The mutations were identified with polymerase chain reaction followed by restriction fragment length polymorphism (RFLP) analysis. The prevalence of the Asp299Gly and the Thr399Ile mutant allele was 4.1% (10/244) and 4.5% (11/244) among periodontitis patients. For the healthy controls the prevalence was 3.3% (8/244) for the Asp299Gly (P = 0.810) and 3.7% (9/244) for the Thr399Ile mutant allele (P = 0.819). The Arg753Gln mutant allele was found in 2.9% (7/244) of the periodontitis subjects as compared to 4.1% (10/244) in the control group (P = 0.622). The Arg677Trp mutant allele was not found in any of the study subjects. Unlike in ulcerative colitis there was not observed an association between chronic periodontitis and the various mutations of the TLR 2 and 4 gene.     

Common BRCA1 variants and susceptibility to breast and ovarian cancer in the general population

Most multiple case families of young onset breast cancer and ovarian cancer are thought to be due to highly penetrant mutations in the predisposing genes BRCA1 and BRCA2. However, these mutations are uncommon in the population and they probably account for only a few percent of all breast cancer incidence. A much larger fraction of breast cancer might, in principle, be due to common variants which confer more modest individual risks. There are several common polymorphisms in the BRCA1 gene which generate amino acid substitutions. We have examined the frequency of four of these polymorphisms: Gln356Arg, Pro871Leu, Glu1038Gly and Ser1613Gly in large series of breast and ovarian cancer cases and matched controls. Due to strong linkage disequilibrium, these four sites generate only three haplotypes with a frequency > 1.3%. The most common haplotypes, defined by the alleles Gln356Pro871Glu1038Ser1613 and Gln356Leu871Gly1038Gly1613, have frequencies of 0.57 and 0.32 respectively, and these frequencies do not differ significantly between patient and control groups. Thus the most common polymorphisms of the BRCA1 gene do not make a significant contribution to breast or ovarian cancer risk. However, our data suggest that the Arg356 allele may have a different genotype distribution in breast cancer patients from that in controls (Arg356 homozygotes are more frequent in the control groups, P = 0.01), indicating that it may be protective against breast cancer. If this finding can be confirmed, it may provide an insight into the structural features of the BRCA1 protein that are important for its function.      

Meta-analysis of the association of beta2-adrenergic receptor polymorphisms with asthma phenotypes

BACKGROUND: Two common polymorphisms of the beta2-adrenergic receptor gene (Arg16Gly and Gln27Glu ) have been extensively studied for their possible association with asthma-related phenotypes, but the results of individual studies have been inconclusive. OBJECTIVE: We aimed to integrate quantitatively the available evidence on the association of the Arg16Gly and the Gln27Glu polymorphisms with asthma, nocturnal asthma, asthma severity, and bronchial hyperresponsiveness. METHODS: Meta-analysis of case-control and cohort studies using random effects models. RESULTS: A total of 28 studies were included in the meta-analysis. The summary estimates suggested that neither the Gly16 nor the Glu27 allele contributes to asthma susceptibility overall (odds ratio [OR], 1.01; 95% CI, 0.90-1.13; and OR, 0.95; 95% CI, 0.83-1.09, respectively) or to bronchial hyperresponsiveness (OR, 0.90; 95% CI, 0.77-1.05; and OR, 1.07; 95% CI, 0.94-1.22, respectively). There was a strong association of Gly16 with nocturnal asthma (OR, 2.20; 95% CI, 1.56-3.11) and a less strong association with severe or moderate rather than milder asthma (OR, 1.42; 95% CI, 1.04-1.94). No such effects were seen for the Glu27 allele (OR, 1.02; 95% CI, 0.74-1.40; and OR, 0.82; 95% CI, 0.59-1.14, respectively). Moreover, there was evidence that Gly16 homozygotes had a much higher risk for nocturnal asthma (OR, 5.15; 95% CI, 2.44-10.84) and asthma severity (OR, 2.84; 95% CI, 1.62-4.96) than the Arg16 homozygotes. CONCLUSION: The Gly16 allele of the beta2-adrenergic receptor gene predisposes to nocturnal asthma, and this may also explain the association with asthma severity. Neither polymorphism modulates the risk for bronchial hyperresponsiveness or mild asthma.