1,721,160 research outputs found
Synergistic Interaction of Angiotensinogen and Angiotensin-conver ting Enzyme Genes in Predicting Coronary Ar ter iosclerosis
No full textAngiotensinogen (AGT) and angiotensin-converting enzyme (ACE) gene
polymorphisms have been implicated in the pathogenesis of coronary artery disease
(CAD) and myocardial infarction (MI). However, conclusions are inconsistent and
there are few combination analysis of the AGT and ACE genes in relation to CAD
and MI. We therefore study 255 Taiwanese people, including 171 CAD patients and
84 non-CAD controls. A novel stepdown polymerase chain reaction (PCR) was used
to genotype the ACE insertion/deletion(I/D) polymorphism and a stepdown PCRdirect
sequencing to genotype the M235T and T174M variants of the AGT gene.
The results showed that the 235T allele and TT genotype frequencies of the AGT gene
were 82% and 65% respectively in the non-CAD group vs. 83% and 68% in the CAD
group (p>0.05). The 174T allele and TT genotype frequencies were 92% and 86% in
the non-CAD group vs. 89% and 80% in the CAD group (p>0.05). The D allele and
DD genotype frequencies of the ACE gene were 64% and 40% respectively in the
non-CAD group vs. 69% and 46% in the CAD group (p>0.05). There was no
difference of AGT or ACE gene polymorphism in subjects with MI, low risk, or
different severities of CAD. However, subjects with double homozygosity of
235TT/DD genotype had a higher prevalence (75%) of CAD than those with
235TT/(ID+II) (52%) or (235MT+MM)/DD (56%). The odds ratio was 2.61 (95%
CI 1.88 to 3.61). Subjects with double heterozygosity of (235MT+MM)/(ID+II) also
had a higher prevalence (71%) of CAD. The odds ratio was 2.14 (95% CI 1.48 to
3.09). Our data show that no association between each single gene polymorphism of
the AGT and ACE and coronary heart disease can be found in the Taiwanese
population. However, there is a synergistic gene effect that confers an increased risk
for CAD
A Polymorphism in the Beta 1 Adrenergic Receptor Is Associated with Resting Heart Rate
No full textResting heart rate is significantly associated with cardiovascular morbidity and mortality. However, the extent to which resting heart rate is genetically determined is poorly understood, and no genes have been found that contribute to variation in resting heart rate. Because signaling through the beta1 adrenergic receptor is a key determinant of cardiac function, we tested whether polymorphisms in this receptor are associated with resting heart rate. A cohort of 1 1,000 individuals of Chinese and Japanese descent, from nuclear families, was genotyped for two polymorphisms, resulting in a serine/glycine substitution at amino acid 49 (Ser49Gly) and an arginine/ glycine substitution at residue 389 (Arg389 Gly), in the beta 1 adrenergic receptor. For comparison, polymorphisms in the beta2 and beta3 adrenergic receptors were also evaluated. The Ser49Gly polymorphism was significantly associated (P =. 0004) with resting heart rate, independent of other variables, such as body-mass index, age, sex, ethnicity, exercise, smoking, alcohol intake, hypertension status, and treatment with beta blockers. The data support an additive model in which individuals heterozygous for the Ser49Gly polymorphism had mean heart rates intermediate to those of either type of homozygote, with Ser homozygotes having the highest mean heart rate and with Gly homozygotes having the lowest. Neither the Arg389Gly polymorphism in the beta1 adrenergic receptor nor polymorphisms in the beta2 and beta3 adrenergic receptors were associated with resting heart rate. The heritability of heart rate was 39.7% +/- 7.1% (P < 10(-7))
Peripheral and Intracardiac Concentrations of Atrial Natriuretic Peptide in Patients with Heart Diseases
No full textThe Glycine Allele of a Glycine/Arginine Polymorphism in the Beta2- Adrenergic Receptor Gene Is Associated with Essential Hypertension in a Population of Chinese Origin
No full textBACKGROUND: Several studies implicate polymorphisms in the human beta- adrenergic receptor gene (ADRB2) in the susceptibility to hypertension. We sought to replicate these results in a population of Chinese origin primarily from Taiwan and the San Francisco Bay area. METHODS: We genotyped >800 hypertensive subjects and individuals with low-normal blood pressure that were derived largely from the same families as the hypertensive patients for three polymorphisms in the ADRB2 gene: a C/T transition at position 47 (C-47T) in the 5' leader cistron; another C/T transition that results in a glycine/ arginine substitution at codon 16 ( Gly16Arg), and a G/C transversion that causes a glutamate/glutamine substitution at codon 27 (Glu27Gln). RESULTS: The Gly16Arg was significantly associated with hypertension (P < .03). Under a dominant model, for hypertension the relative risk for the Gly/Gly and Gly/Arg genotypes versus the Arg/Arg genotype was 1.35 (95% confidence limits [CL] 1.08, 1.70); for low-normal blood pressure the relative risk was 0.79 (95 % CL 0.66, 0.94). This polymorphism explained approximately 1% of the variance in systolic and diastolic blood pressures in our study population . There was no evidence of association between the C-47T and Glu27Gln polymorphisms and hypertension in this population. CONCLUSIONS: The Glyl6 allele in the beta2- adrenergic receptor gene is a susceptibility allele for essential hypertension in a population of Chinese origin
A Flexible Computational Framework for Detecting, Characterizing, and Interpreting Statistical Patterns of Epistasis in Genetic Studies of Human Disease Susceptibility
No full textDetecting, characterizing, and interpreting gene-gene interactions or epistasis in studies of human disease susceptibility is both a mathematical and a computational challenge. To address this problem, we have previously developed a multifactor dimensionality reduction (MDR) method for collapsing high-dimensional genetic data into a single dimension (i.e. constructive induction) thus permitting interactions to be detected in relatively small sample sizes. In this paper, we describe a comprehensive and flexible framework for detecting and interpreting gene- gene interactions that utilizes advances in information theory for selecting interesting single-nucleotide polymorphisms ( SNPs), MDR for constructive induction, machine learning methods for classification, and finally graphical models for interpretation. We illustrate the usefulness of this strategy using artificial datasets simulated from several different two-locus and three-locus epistasis models. We show that the accuracy, sensitivity, specificity, and precision of a naive Bayes classifier are significantly improved when SNPs are selected based on their information gain (i.e. class entropy removed) and reduced to a single attribute using MDR. We then apply this strategy to detecting, characterizing, and interpreting epistatic models in a genetic study (n = 500) of atrial fibrillation and show that both classification and model interpretation are significantly improved. (c) 2005 Elsevier Ltd. All rights reserved
Characteristics of Chinese Patients with Symptomatic Brugada Syndrome in Taiwan
No full textSince 1992, the Brugada syndrome has been increasingly recognized worldwide, although its incidence and distribution remain unclear. In Asia , several cases have been reported in Japan, Thailand, Singapore, and Vietnam. However, little information is available from the Chinese population. Since June 1997, we have identified 10 patients with the diagnosis of the Brugada syndrome from six hospitals in Taiwan. All patients were male with the mean age of 46 +/- 7 years (range 36-61). They all had a normal chemistry profile, coronary angiography and echocardiography . Clinical presentations varied from seizure and syncope to sudden cardiac death. MRI and ultrafast CT of the heart did not show any abnormalities. Sustained ventricular tachycardia/ventricular fibrillation (VF) was induced in 7 of 8 patients who underwent an electrophysiologic study. The pharmacological provocation test was positive in 4 of 5 patients. One of the 4 patients who had a genetic study showed SCN5A gene mutation. An implantable cardioverter defibrillator ( ICD) was implanted in 8 patients. During a mean follow-up of 29 +/- 17 months (range 2-54), 3 of 8 patients who had an ICD received appropriate ICD discharges after implantation. These 3 patients who were subsequently treated with antiarrhythmic agents have had no further recurrent ICD discharges. Two patients who refused ICD implantation are alive and well without taking antiarrhythmic agents. Our study showed that the clinical characteristics of our patients are similar to those described in the literature and that ICD is an effective treatment modality for patients with recurrent VF. However, antiarrhythmic agents may be beneficial for suppressing arrhythmia recurrences in selected patients. Copyright 2003 S. Karger AG, Base
高血壓的基因研究
No full text隨著社會的發展，高血壓的盛行率也跟著升高。數種家族性高血壓已被確定由單基因 突變所造成。這些研究也為高血壓與基因遺傳有關奠下了證據。本態性高血壓被認為 是由多種基因的變異與環境的互動所造成。由於生理與血壓調控有關的基因稱為候選 基因，大多數本態性高血壓的基因研究在於尋找本態性高血壓和候選基因的相關性。 已有報告本態性高血壓與少數候選基因，例如血管張力素原基因，具有有意義的相關 ；然而其相關性仍因種族而有差別。也有利用多個標幟 ( markers) 進行全基因體掃 瞄，並發現數個與本態性高血壓相關的局部區域 (locus)；它們分佈於染色體2p，2q ，5q，6q，15q，17，和18q 等。一般預期高血壓動物之基因研究將有助於尋找本態 性高血壓的致病基因，目前已有約二十個大鼠之高血壓相關的局部區域被定位。高血 壓的基因研究將有助於高血壓的早期診斷、高血壓及心臟血管危險因子的分析、以及 未來更個人化的治療。然而我們也要瞭解高血壓基因研究的複雜性而且高血壓的基因 變異可能因種族而有差異。Hypertension is a rising problem in the developed countries. Some rare familial hypertensive syndromes have been found to be caused by monogenic mutations. Essential hypertension is generally regarded as a complex genetic trait caused by multiple genes. The polygenic effects on blood pressure are modulated by gene-gene and gene- environment interactions. Most investigations for genetic causes of essential hypertension were approached with candidate genes, and a few candidate genes, such as angiotensinogen gene, were reported to be associated with essential hypertension, though the reports from different populations were still conflicting. Genome-wide scans with multiple markers have mapped several loci associated with blood pressure. The loci reported were on chromosomes 2p, 2q, 5q, 6q, 15q, 17, and 18q respectively . However, to date, no genotype had been conclusively linked to essential hypertension. It has long been hoped that genetic research on hypertensive animals, such as rats, will facilitate our understanding of the genetics of human essential hypertension. So far, more than twenty loci were reported to be associated with blood pressure in rats. More understanding of the genetic basis of essential hypertension should be possible in the future and would be expected to help earlier diagnosis, more effective risk factor assessment and more individualized treatment of hypertension. However, the difficulty of genetic analysis for essential hypertension and the possibility of inter- population differences in genetic factors should be kept in mind
Vectorcardiograms in Normal Adult Rats:with Special Reference to Its Pattern Different from Man
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