The role of G protein β3 subunit polymorphisms C825T, C1429T, and G5177A in Turkish subjects with essential hypertension

Hypertension is a multifactorial disorder that constitutes a major risk factor for the cardiovascular system. Heterotrimeric G-proteins, which couple receptors for diverse extracellular enzymes or ion channels, are correlated with disease mechanisms. Several studies have demonstrated an association between G protein polymorphisms and essential hypertension in some populations, although contradictive results also exist. In this study, we have investigated the potential role of the C825T, C1429T, and G5177A polymorphisms of the β3 subunit of G-proteins in essential hypertension in a group of Turkish subjects. Genomic DNA from 106 normotensive individuals (117.4 ± 13.1, 75.2 ± 10.5; systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels, respectively) and 101 hypertensive subjects (152.3 ± 18.0, 92.5 ± 11.6; SBP and DBP levels, respectively) were studied by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct sequencing methods for these polymorphisms. Allele frequencies of the polymorphisms were consistent with Hardy Weinberg equilibrium, except for the C825T polymorphism (χ(2) = 7.8). The frequencies of the 825T and 1429T variants were higher in hypertensive subjects compared to those of controls. Differences between hypertensives and controls were not statistically significant, though difference was very close to significance for C825T (p = 0.056 and 0.099 for 825T and 1429T, respectively). T allele frequency in overall population showed significant association with hypertension for C825T (0.0134). The prevalence of the 5177A-variant was very low and all subjects carrying it were heterozygotes in both groups.     

Better identification of patients who benefit from implantable cardioverter defibrillators by genotyping the G protein β3 subunit (GNB3) C825T polymorphism

AIMS : There is a need for better identification of patients at high risk for malignant arrhythmias who would benefit from implantable cardioverter defibrillators (ICD). The purpose of this study was to assess whether the C825T polymorphism in the G-protein beta3 subunit gene, GNB3, might serve as a genetic marker for recurrent ventricular arrhythmias. METHODS AND RESULTS : Genotyping was performed in 82 patients with ischemic heart disease treated with an ICD for primary and secondary prevention of cardiac arrhythmias. The Kaplan-Meier method was used to estimate the probability of remaining free from VT/VF with cycle length (CL) < 330 ms that required treatment by the ICD. Genotyping yielded 7 individuals homozygous for the 825T allele (TT), 36 homozygous for the C825 allele (CC), and 39 heterozygotes (CT). Multivariate analysis revealed that the C825T polymorphism (P = 0.004), left ventricular ejection fraction (P = 0.009), and QRS-duration (P = 0.039) were independent determinants of severe ventricular arrhythmias. Homozygous carriers of the C825 allele had a 3.9-fold risk for severe ventricular arrhythmias. CONCLUSION : The results from this pilot study suggest that the C825T polymorphism may have a modifying effect on the propensity towards life-threatening arrhythmias. Genotyping the C825T polymorphism may help to better identify individuals at high risk for life-threatening arrhythmias who benefit from ICD therapy.     

G-protein β3 Subunit Gene Variant (C825T) is Unlikely to Have a Significant Influence on Serum Total Cholesterol Level in Japanese Workers

We investigated the association between hypercholesterolemia or serum total cholesterol level and the C825T polymorphism in the G-protein β3 subunit gene in Japanese workers using multivariate analysis to control possible confounding factors. The study subjects were 1,452 males and 1,169 females selected from 3,834 males and 2,591 females. Hypercholesterolemia was classified as either a total serum cholesterol $5.7 mmol/L (220 mg/dL) or taking lipid-lowering medication. The statistical power of the study was estimated as 99.9% based on total cholesterol levels of previous significant studies in Caucasians and Japanese. The genotype distributions in males with hypercholesterolemia (CC = 78, CT = 154, TT = 78) and females (CC = 60, CT = 137, TT = 52) were not significantly different from normal males (CC = 280, CT = 595, TT = 267) or females (CC = 234, CT = 501, TT = 185). Allele distributions also were not significantly different in either sex. Logistic regression analysis of hypercholesterolemia data and analysis of variance, t-test and multiple regression of serum total cholesterol data demonstrated no significant relationship with the C825T genotype. Despite sufficient statistical power, this study did not demonstrate a significant influence of C825T on hypercholesterolemia or serum total cholesterol level. The targeting of this polymorphism therefore is unlikely to be beneficial in preventing hypercholesterolemia in the general Japanese population.     

GNB3基因C825T多态性与心血管疾病

GNB3基因C825T多态位点的发现已有五年历程，它在不同种族中的分布不同。由于G蛋白在信号转导过程中起“分子开关”作用，介导许多血管活性及增殖有关的细胞内效应，所以该位点的多态性与心血管疾病的关系受到广泛关往。目前已确定该位点与白种人高血压、肥胖显著相关。在亚洲人群的研究资料较少，目前缺乏它与高血压、肥胖相关的证据。它与左室肥厚、冠心病发生的关联性尚存争议。     

The β-globin promoter -71 C>T mutation is a β+ thalassemic allele

A novel β-globin gene promoter (-71 C>T) nucleotide change was recently posted to the HbVar database (ID 2701) without precision on phenotype and ethnicity. We found the same change in compound heterozygosity with Hb S [β6(A3)Glu>Val] in an Omani family with almost equal expression of Hb A and Hb S. This suggested that the -71 C to T mutation may be a mild β-thalassemic allele. Subsequent search found three other independent cases with the same atypical Hb A:Hb S ratio, further confirming the mild thalassemic feature of this mutation. In addition, molecular screening of a set of subjects (with only Hb A) with borderline Hb A(2) or MCV values revealed the presence of -71 C>T change in heterozygous state, altogether assigning the mutation as a mild β(+) thalassemic allele. In a region such as Oman, where several genetic conditions of the red blood cell coexist (α- and β-thalassemia, Hb S, Hb D, Hb E) in significant frequencies, it is crucial to decipher the molecular basis of these atypical forms of β(+) thalassemias, especially in a genetic counseling setting.     

NMR analysis of G-protein βγ subunit complexes reveals a dynamic Gα-Gβγ subunit interface and multiple protein recognition modes

G-protein βγ (Gβγ) subunits interact with a wide range of molecular partners including: Gα subunits, effectors, peptides, and small molecule inhibitors. The molecular mechanisms underlying the ability to accommodate this wide range of structurally distinct binding partners are not well understood. To uncover the role of protein flexibility and alterations in protein conformation in molecular recognition by Gβγ, a method for site-specific ¹⁵N-labeling of Gβ-Trp residue backbone and indole amines in insect cells was developed. Transverse Relaxation Optimized Spectroscopy-Heteronuclear Single-Quantum Coherence Nuclear Magnetic Resonance (TROSY-HSQC NMR) analysis of ¹⁵N-Trp Gβγ identified well-dispersed signals for the individual Trp residue side chain and amide positions. Surprisingly, a wide range of signal intensities was observed in the spectrum, likely representing a range of backbone and side chain mobilities. The signal for GβW99 indole was very intense, suggesting a high level of mobility on the protein surface and molecular dynamics simulations indicate that GβW99 is highly mobile on the nanosecond timescale in comparison with other Gβ tryptophans. Binding of peptides and phosducin dramatically altered the mobility of GβW99 and GβW332 in the binding site and the chemical shifts at sites distant from the direct binding surface in distinct ways. In contrast, binding of Gα_i1-GDP to Gβγ had relatively little effect on the spectrum and, most surprisingly, did not significantly alter Trp mobility at the subunit interface. This suggests the inactive heterotrimer in solution adopts a conformation with an open subunit interface a large percentage of the time. Overall, these data show that Gβγ subunits explore a range of conformations that can be exploited during molecular recognition by diverse binding partners.     

The β3-Adrenergic System and β3-Adrenergic Agonists

Reviews in Endocrine and Metabolic Disorders -     

Elucidation of G-protein and β-arrestin functional selectivity at the dopamine D2 receptor

The neuromodulator dopamine signals through the dopamine D2 receptor (D₂R) to modulate central nervous system functions through diverse signal transduction pathways. D₂R is a prominent target for drug treatments in disorders where dopamine function is aberrant, such as schizophrenia. D₂R signals through distinct G-protein and β-arrestin pathways, and drugs that are functionally selective for these pathways could have improved therapeutic potential. How D₂R signals through the two pathways is still not well defined, and efforts to elucidate these pathways have been hampered by the lack of adequate tools for assessing the contribution of each pathway independently. To address this, Evolutionary Trace was used to produce D₂R mutants with strongly biased signal transduction for either the G-protein or β-arrestin interactions. These mutants were used to resolve the role of G proteins and β-arrestins in D₂R signaling assays. The results show that D₂R interactions with the two downstream effectors are dissociable and that G-protein signaling accounts for D₂R canonical MAP kinase signaling cascade activation, whereas β-arrestin only activates elements of this cascade under certain conditions. Nevertheless, when expressed in mice in GABAergic medium spiny neurons of the striatum, the β-arrestin–biased D₂R caused a significant potentiation of amphetamine-induced locomotion, whereas the G protein-biased D₂R had minimal effects. The mutant receptors generated here provide a molecular tool set that should enable a better definition of the individual roles of G-protein and β-arrestin signaling pathways in D₂R pharmacology, neurobiology, and associated pathologies.G protein-coupled receptors (GPCRs) are the largest receptor family and transmit the physiological effects of numerous biologically active molecules. GPCR signal transduction cascades account for diverse genomic, biochemical, cellular, and behavioral responses including cell fate determination, developmental reprogramming, olfactory, taste and light sensation, as well as complex behaviors mediated by neuromodulators (1). The diversity of responses to a particular hormone or neuromodulator is dictated not only by its cognate receptor but also by the ability of that receptor to engage distinct signaling pathways. For a number of GPCRs, their propensity to activate distinct G proteins can elicit diverse responses depending on the cellular environment (2). However, an even more subtle but intriguing mode of signaling has been attributed to the ability of a receptor to activate signaling pathways independent of G-protein activation, through the scaffolding of signaling complexes by β-arrestin, a component of the GPCR desensitization and internalization machinery (3). These two signaling modes harbor distinct functional properties, and in instances the same ligand can act as an agonist for one pathway but antagonist at the other. The selective or biased activation of a given pathway is commonly referred to as “functional selectivity” and can be easily demonstrated in heterologous systems especially when biased small molecule ligands are available (4). Biased GPCR ligands may have high therapeutic potential as these receptors represent the largest targets of drugs on the market. However, determining the functional contributions of G-protein and β-arrestin signaling pathways to the biological actions of an endogenous ligand acting upon its receptor still remains a challenging undertaking.Dopamine (DA) is a neuromodulator that is known to regulate movement, reward, cognition, emotion, and affect. The dopamine D2 receptor (D₂R) is a prominent GPCR that mediates the actions of DA. All typical antipsychotics, such as haloperidol, are potent D₂R blockers (5), whereas atypical antipsychotics, such as aripiprazole and clozapine, have unique pharmacology, exhibiting weak partial agonist activity at D₂R or reduced antagonist efficacy, respectively (6). Previous studies have demonstrated the ability of D₂Rs to engage different signal transduction pathways depending on the cellular complement of G proteins as well as their ability to regulate different physiological processes (7–9). β-arrestin 2 knockout mice provided robust behavioral and biochemical evidence for a critical D₂R/β-arrestin signaling pathway in the striatum (10). Furthermore, neuronal selective deletion of GSK3β, a putative D₂R/β-arrestin 2 effector, could reproduce the pharmacological blockade of D₂Rs with antipsychotics (11). Although these studies suggest that D₂Rs, like many other GPCRs, use pleiotropic signaling pathways to mediate their effects, the brain DA system is uniquely complex, as diverse responses may also rely upon many other determinants. One well-documented variable is the mode of stimulation of DA receptors, which is a function of the tonic or phasic release of DA (12). The expression profile of D₂R is also complex, being expressed not only in DA synthesizing neurons of the substantia nigra and ventral tegmental area where they function as presynaptic autoreceptors but also in GABAergic medium spiny neurons (MSNs), cholinergic interneurons of the striatum, and cortical neurons (13), where they function as postsynaptic receptors. Thus, understanding the contributions of functional selectivity at D₂R in intact biological systems is a challenge that cannot be elucidated in heterologous systems alone. To develop tools where this challenge can begin to be addressed, the Evolutionary Trace (ET) (14) approach was used to engineer D₂R mutants that selectively interact with either G proteins or β-arrestins, designated ^[Gprot]D₂R and ^[βarr]D₂R, respectively. These mutants show separation of G-protein and β-arrestin interactions, and expression of these mutants in vivo in the mouse striatum provides proof-of-concept for their biological activity and discrete functions.     

Is there an association between GNbeta3-C825T genotype and lower functional gastrointestinal disorders?

BACKGROUND & AIMS: GNbeta3 influences G-protein translation of a majority of ligand-receptor activations. It has been reported that functional dyspepsia (FD) is associated with homozygous genotypes of the C825T polymorphism in the GNbeta3 gene. It is unknown whether the GNbeta3 genotype is associated with lower functional gastrointestinal disorders (FGID). We aimed to compare the prevalence of the different GNbeta3-C825T genotypes in patients with lower FGID and healthy controls and to test the associations of these genetic variations with subgroups of irritable bowel syndrome (IBS), functional abdominal pain (FAP), lower FGID-FD overlap, and high somatic symptom scores. METHODS: GNbeta3-C825T polymorphism was analyzed in DNA from blood samples of 233 patients with lower FGID and 152 healthy controls. A validated bowel questionnaire characterized the FGID phenotype: 82 with IBS constipation, 94 with IBS diarrhea, 38 with IBS alternating bowel function, and 19 with FAP. There were 159 patients with lower FGID and overlap FD using Rome II criteria. Regression analyses assessed associations of the GNbeta3 genotypes with lower FGID as a group, and subgroups of FGID and somatic symptom scores. RESULTS: GNbeta3-C825T genotype distributions were similar between healthy controls (50.7% CC, 40.8% TC) and patients with lower FGID (8.6% TT, 51.5% CC, 40.8% TC, and 7.7% TT). There were no significant associations of GNbeta3-C825T polymorphism with lower FGID overall or with the separate symptom subgroups including IBS, FAP, lower FGID-FD overlap, or high somatic symptom scores. CONCLUSIONS: In contrast to the reported association with FD, GNbeta3-C825T polymorphism is not associated significantly with lower FGID, with different IBS or FAP phenotypes, or lower FGID-FD overlap.     

PKA catalytic subunit compartmentation regulates contractile and hypertrophic responses to β-adrenergic signaling

β-Adrenergic signaling is spatiotemporally heterogeneous in the cardiac myocyte, conferring exquisite control to sympathetic stimulation. Such heterogeneity drives the formation of protein kinase A (PKA) signaling microdomains, which regulate Ca^2 + handling and contractility. Here, we test the hypothesis that the nucleus independently comprises a PKA signaling microdomain regulating myocyte hypertrophy. Spatially-targeted FRET reporters for PKA activity identified slower PKA activation and lower isoproterenol sensitivity in the nucleus (t₅₀ = 10.6 ± 0.7 min; EC₅₀ = 89.0 nmol/L) than in the cytosol (t₅₀ = 3.71 ± 0.25 min; EC₅₀ = 1.22 nmol/L). These differences were not explained by cAMP or AKAP-based compartmentation. A computational model of cytosolic and nuclear PKA activity was developed and predicted that differences in nuclear PKA dynamics and magnitude are regulated by slow PKA catalytic subunit diffusion, while differences in isoproterenol sensitivity are regulated by nuclear expression of protein kinase inhibitor (PKI). These were validated by FRET and immunofluorescence. The model also predicted differential phosphorylation of PKA substrates regulating cell contractility and hypertrophy. Ca^2 + and cell hypertrophy measurements validated these predictions and identified higher isoproterenol sensitivity for contractile enhancements (EC₅₀ = 1.84 nmol/L) over cell hypertrophy (EC₅₀ = 85.9 nmol/L). Over-expression of spatially targeted PKA catalytic subunit to the cytosol or nucleus enhanced contractile and hypertrophic responses, respectively. We conclude that restricted PKA catalytic subunit diffusion is an important PKA compartmentation mechanism and the nucleus comprises a novel PKA signaling microdomain, insulating hypertrophic from contractile β-adrenergic signaling responses.     

高血压病患者G蛋白β3基因C825T和eNOS基因G894T多态性研究

目的　观察高血压病 (EH)患者G蛋白 β3亚单位基因 (GNB3)C82 5T多态性和内皮一氧化氮合酶 (eNOS)基因G894T多态性 ,探讨EH发生的遗传学机制。方法　EH患者 112例 ,对照组 112例。取血标本提取DNA ,用PCR方法扩增目的基因 ,用限制性内切酶 (BanⅡ、BseDI)酶切PCR产物用于基因分型。结果　EH患者GNB3C82 5T基因型分布 (基因型频率CC =0 34,CT =0 5 3 ,TT =0 13)与对照组有显著性差异 (基因型频率CC =0 5 9,CT =0 36 ,TT =0 0 5。χ2 =6 9,P <0 0 5 ) ;82 5T等位基因携带者与CC纯合子比较有较高的患EH的危险 (OR =2 2 ,95 %CI1 1～ 4 6 )。eNOS各基因型在EH的分布与对照组无显著性差异。Logistic回归分析显示 ,GNB3 82 5T等位基因与EH关联最密切。结论GNB3基因C82 5T多态性的 82 5T等位基因是EH发病的遗传危险因子。eNOS基因G894T多态性在EH发病中不起直接重要作用。     

G蛋白β3亚单位基因C825T多态性与原发性高血压

目的 探讨G蛋白β3亚单位基因C825T多态性与国人原发性高血压以及高血压左室肥厚（LVH）、血脂水平之间的关系。方法 采用多聚酶链式反应结合限制性内切酶片段长度多态分析方法（PCR－RFLP）检测79例健康人和146例高血压患者的G蛋白β3亚单位基因C825T多态性,体重指数（BMI）,并测定128例高血压患者的总胆固醇（Tch)、甘油三酯（TG）、空腹血糖（Glu)及肌酐（Cr)浓度和103例高血压患者的左室质量指数（LVMI）。结果（1）高血压组G蛋白β3亚单位基因型频率（CC24．7％、CT69．2％、TT6．2％）、等位基因频率（C59．2％、T40．8％）与正常对照组基因型频率（CC22．8％、CT63．3％、TT13．9％）、等位基因频率（C54．4％、T45．6％）比较无显著性差异;（2）CC基因型患者与CT＋TT基因型患者比较,BMI、LVMI、血脂水平亦无显著性差异。结论 提示G蛋白β3亚单位基因C825T多态性可能与中国人原发高血压及其LVH、血脂水平无关。     

G蛋白β3亚单位基因C825T多态性与原发性高血压

目的探讨G蛋白β3亚单位基因C825T多态性与国人原发性高血压以及高血压左室肥厚(LVH)、血脂水平之间的关系.方法采用多聚酶链式反应结合限制性内切酶片段长度多态分析方法(PCR-RFLP)检测79例健康人和146例高血压患者的G蛋白β3亚单位C825T多态性、体重指数(BMI),并测定128例高血压患者的总胆固醇(Tch)、甘油三脂(TG)、空腹血糖(Glu)及肌酐(Cr)浓度和103例高血压患者的左室质量指数(LVMI).结果(1)高血压组G蛋白β3亚单位基因型频率(CC24.7%、CT69.2%、TT6.2%)、等位基因频率(C59.2%、T40.8%)与正常对照组基因型频率(CC22.8%、CT63.3%、TT13.9%)、等位基因频率(C54.4%、T45.6%)比较无显著性差异;(2)CC基因型患者与CT+TT基因型患者比较,BMI、LVMI、血脂水平间亦无显著性差异.结论提示G蛋白β3亚单位基因C825T多态性可能与中国人原发性高血压及其LVH、血脂水平无关.     

老年冠心病患者G蛋白β3亚单位C825T基因多态性研究

目的 探讨G蛋白β3亚单位C825T基因多态性与老年冠心病的关系.方法 应用PCR-RFLP对122例冠心病患者和117例年龄、性别相匹配的正常对照组人群进行G蛋白β3亚单位C825T基因多态性分析. 结果 G蛋白β3亚单位C825T基因多态性分布在冠心病组和对照组均符合Hardy -Weinberg平衡定律,表明样本具有群体代表性.T等位基因频率在冠心病组（55.7%）显著高于正常对照组（40.2%）（P＜0.05）.Logistic回归分析显示,校正其他危险因素后,T等位基因携带者或TT纯合子者发生冠心病的OR值分别为1.48 和2.21.结论 G蛋白β3亚单位C825T基因多态性与老年冠心病的发病有关,T等位基因有可能是冠心病发病的遗传危险因素之一.     

Dynamic regulation of β1 subunit trafficking controls vascular contractility

Ion channels composed of pore-forming and auxiliary subunits control physiological functions in virtually all cell types. A conventional view is that channels assemble with their auxiliary subunits before anterograde plasma membrane trafficking of the protein complex. Whether the multisubunit composition of surface channels is fixed following protein synthesis or flexible and open to acute and, potentially, rapid modulation to control activity and cellular excitability is unclear. Arterial smooth muscle cells (myocytes) express large-conductance Ca²⁺-activated potassium (BK) channel α and auxiliary β1 subunits that are functionally significant modulators of arterial contractility. Here, we show that native BKα subunits are primarily (∼95%) plasma membrane-localized in human and rat arterial myocytes. In contrast, only a small fraction (∼10%) of total β1 subunits are located at the cell surface. Immunofluorescence resonance energy transfer microscopy demonstrated that intracellular β1 subunits are stored within Rab11A-postive recycling endosomes. Nitric oxide (NO), acting via cGMP-dependent protein kinase, and cAMP-dependent pathways stimulated rapid (≤1 min) anterograde trafficking of β1 subunit-containing recycling endosomes, which increased surface β1 almost threefold. These β1 subunits associated with surface-resident BKα proteins, elevating channel Ca²⁺ sensitivity and activity. Our data also show that rapid β1 subunit anterograde trafficking is the primary mechanism by which NO activates myocyte BK channels and induces vasodilation. In summary, we show that rapid β1 subunit surface trafficking controls functional BK channel activity in arterial myocytes and vascular contractility. Conceivably, regulated auxiliary subunit trafficking may control ion channel activity in a wide variety of cell types.Ion channels control physiological functions in virtually all cell types (1). Current (I) generated by an ion channel population is a product of the number of channels (N), open probability (P_o), and single-channel current (i), such that I = N⋅P_o⋅i. Previous studies have focused on identifying physiological and pathological mechanisms that regulate the P_o of plasma membrane-resident ion channels. In contrast, mechanisms that control the number of functional plasma membrane ion channels (N) and their regulatory auxiliary subunits in native cell types are unclear. A conventional view is that ion channels assemble with their auxiliary subunits before anterograde trafficking and plasma membrane insertion of the protein complex. Auxiliary subunits can modulate ion channel surface expression and activity, but it is unclear whether the multisubunit composition of surface channels is fixed following protein synthesis or flexible and open to acute and rapid modulation (2–4). Some recombinant ion channel proteins, including large-conductance calcium (Ca²⁺)-activated potassium (BK) α subunits, can traffic to the plasma membrane in the absence of their regulatory auxiliary subunits (5–9). This stimulated us to investigate the hypothesis that physiological stimuli rapidly modulate surface levels of auxiliary subunits to control functional ion channel activity. Such a mechanism would fine tune ion channel activity to control cell functionality. To test this hypothesis, we studied trafficking and surface expression of native BK channel subunits in smooth muscle cells (myocytes) of small arteries that regulate regional organ blood flow and systemic blood pressure (10).BK channels are expressed in a wide variety of mammalian cell types and regulate functions including arterial contractility, neurotransmission, and endocrine secretion (11). BK channels are heterotetramers of pore-forming α subunits that can also contain auxiliary β subunits, of which four are known (β1 to -4) (12, 13). β subunits are expressed in a tissue-specific manner and modulate BK channel Ca²⁺ sensitivity and gating properties to customize cellular functionality (14). Arterial myocytes express β1 subunits, which elevate BK channel Ca²⁺ sensitivity into a concentration range that permits functional coupling to local micromolar intracellular Ca²⁺ transients termed Ca²⁺ sparks (15). β1 subunits are essential for BK channels to control arterial myocyte membrane potential and contractility and to modulate systemic blood pressure (16, 17). Ca²⁺ spark to BK channel coupling is weak in β1 subunit knockout mice, leading to membrane depolarization, vasoconstriction, and systemic hypertension (14, 15). Pathological alterations in BK channel β1 subunit expression and function are also associated with cardiovascular diseases, including atherosclerosis, stroke, and hypertension (18). Whether physiological signaling mechanisms can control the α-to-β subunit ratio in BK channels to modulate channel activity and myocyte contractility is unclear.     

G蛋白β3亚单位C825T等位基因多态性与原发性高血压的关系

目的 探讨温州地区汉族人群G蛋白β3亚单位(GNB3)C825T等位基因多态性与原发性高血压的相关性.方法 原发性高血压患者109例,正常对照组378例,聚合酶链反应(PCR)/酶解-琼脂糖凝胶电泳检测基因型.结果 (1)温州地区汉族人群GNB3 825T等位基因频率为43.5%,与其他人种的该基因频率显著不同.(2)原发性高血压组的TT基因型携带率明显升高(P＜0.01),TT基因型携带者与CT型携带者比较,其致高血压的比数比(OR值)为2.5(P＜0.01);TT型与CC型比,其OR值为2.4(P＜0.01);等位基因T与C比较,致高血压的OR值为1.5(P＜0.05).(3)GNB3不同基因型间的血压水平比较,收缩压CT和TT携带者与CC携带者比较均增高(P＜0.05和P＜0.01),TT携带者与CT携带者比较亦有升高(P＜0.01),舒张压TT携带者比CC携带者增高(P＜0.05),而CT携带者与CC携带者比较差异无显著性(P＞0.05),TT携带者与CT携带者比较,收缩压和舒张压均增高(P＜0.01和P＜0.05).结论 GNB3 825T基因型可作为早期预测原发性高血压的遗传学指标之一.