Tsu-Shiu Hsu

Angiotensinogen and angiotensin-I converting enzyme gene polymorphisms and the risk of coronary artery disease in Chinese

Abstract The homozygous deletion allele (DD) of the angiotensin-I converting enzyme (ACE) gene and the T235 homozygote of the angiotensinogen (AGT) gene have been reported to be correlated with an increased prevalence of coronary artery disease (CAD) and myocardial infarction (MI). The importance of the DD genotype and T235 homozygote as genetic risk factors for CAD in Chinese remains uncertain. This study included 426 patients who underwent coronary angiography and 180 healthy subjects without clinical evidence of CAD. Coronary angiography identified 268 patients with CAD (CAD group) and 158 patients without CAD. The healthy subjects and patients without angiographic evidence of CAD constituted the control group. Three polymorphisms were studied: an insertion/deletion (I/D) polymorphism of the ACE gene and the T174 M and M235T polymorphisms of the AGT gene. No association was found between any of the three studied polymorphisms and the risk of CAD or MI in Chinese using univariate or multivariate analysis. In multivariate analysis, the relative risks were 1.20 (95% confidence interval = 0.91–1.61, P = 0.20) for the DD genotype, 1.05 (95% CI = 0.82–1.35, P = 0.69) for the T174 homozygote, and 1.19 (95% CI = 0.91–1.55, P = 0.20) for the T235 homozygote. Similarly, no significant difference was found in the frequencies of the DD genotype and the T174 and T235 homozygotes between the control group, the CAD group, the non-MI group, and the MI group when analyzed according to sex, age, or degree of risk. Our data suggest that neither the DD genotype of the ACE I/D polymorphism nor the T174 and T235 homozygotes of the AGT gene confer significant risk for CAD or MI in Chinese.

Interaction between obesity and genetic polymorphisms in the apolipoprotein CIII gene and lipoprotein lipase gene on the risk of hypertriglyceridemia in Chinese

Abstract To understand the effects of the interaction between genetic polymorphisms and obesity on the risk of hypertriglyceridemia (HTG), two polymorphisms, an SstI polymorphism on the apolipoprotein CIII gene and a HindIII polymorphism on the lipoprotein lipase gene, were analyzed in 339 Chinese subjects with (82 cases in the HTG group) or without HTG (257 cases in the control group). Our data revealed that the frequencies of obesity, the SstI minor allele (S2), and the HindIII major allele (H+) in the HTG group were significantly higher than in the control group. Subgroup analysis revealed that the association between these two polymorphisms and HTG occurred predominantly in nonobese subjects and in subjects with the less hypertriglyceridemic genotype of another polymorphism. Multivariate logistic regression analysis showed that all three risk factors (obesity, S2-containing chromosome, and H+ homozygosity) were associated with HTG, and an interaction was found between obesity and H+ homozygosity for the occurrence of HTG. The risk of HTG increased significantly with combinations of risk factors. Subjects can be divided into low or high risk groups for HTG using such combinations. These results provide evidence of interaction between obesity and the HindIII polymorphism of the lipoprotein lipase gene on the risk of HTG.

The C677T mutation of the methylenetetrahydrofolate reductase gene is not associated with the risk of coronary artery disease or venous thrombosis among Chinese in Taiwan.

Objectives: We sought to investigate the association between the methylenetetrahydrofolate reductase (MTHFR) gene C677T mutation and the risk of coronary artery disease (CAD), myocardial infarction (MI) and venous thrombosis (VT) in a Chinese population in Taiwan. Methods: The subjects included 218 CAD patients, 107 VT patients, and their age- and sex-matched controls. DNA was extracted from the blood and genotypes were determined by polymerase chain reaction, restriction mapping with HinfI and gel electrophoresis. Results: The distribution of MTHFR genotypes was similar in the CAD cases and controls; the genotype TT was present in 6.0% of CAD patients, as compared to 6.9% of CAD control subjects (p = 0.165; odds ratio = 0.86; 95% confidence interval = 0.40–1.85). The frequency of the T allele was also similar in CAD cases and controls (25.5% vs. 24.8%; p = 0.788). There was no significant association between TT homozygosity and the risk of MI. The genotype distributions and the frequency of the T allele were also similar in VT cases and controls. Conclusions: Our data suggest that there is no association between the C677T mutation of the human MTHFR gene and the risk of CAD or VT among Chinese in Taiwan.

Importance of hyperhomocysteinemia as a risk factor for venous thromboembolism in a Taiwanese population. A case-control study.

OBJECTIVE To determine the current status of hyperhomocysteinemia, which is a known risk for venous thrombosis (DVT), in Taiwan. SUBJECTS 101 unselected patients with a minimum of one episode of deep leg DVT, either initial inpatients or current compliant outpatients in a teaching hospital. METHODS Various thrombophilic risks, gene polymorphism and clinical predisposition were evaluated. RESULTS AND CONCLUSIONS Patients presented higher fast total plasma homocysteine (hcy) levels than age- and sex-matched controls did (14.1 vs. 9.94 microM). Based on the 95th percentile of control values, hyperhomocysteinemia had a four- to nine-fold risk for DVT, irrespective of clinical predisposition, as well as other thrombophilic risks surveyed. Polymorphism of a metabolizing enzyme, methylenetetrahydrofolate reductase (MTHFR), was not associated with DVT, although homozygous thermolabile mutation tended to have higher plasma hcy levels. Factor V Leiden was absent in analysis of 80 patients. In complete evaluation (hcy, antithrombin (AT), protein S (PS), protein C (PC), lupus anticoagulant (LA), anticardiolipin antibody) of a subset of 83 patients hyperhomocysteinemia was the most prevalent risk (33.7%), with PC or PS deficiencies following (22.9%). Thus, hyperhomocysteinemia is a prominent risk for DVT in Taiwan.

The G1691A mutation of the coagulation factor V gene (factor V Leiden) is rare in Chinese: an analysis of 618 individuals

Abstract To understand the allele frequency of the G1691A mutation of the coagulation factor V gene (factor V Leiden) in Chinese, 618 Chinese individuals, including 54 cases with venous thrombosis, were analyzed. Only one case in the control group was heterozygous for the 1691G allele and the 1691A allele. Our data suggest that the factor V Leiden is rare in Chinese.

Characterization of Atrioventricular Nodal Reentry With Continuous Atrioventricular Node Conduction Curve by Double Atrial Extrastimulation

BACKGROUND Characterization of typical atrioventricular nodal reentrant tachycardia (AVNRT) with continuous AVN conduction (A1A2/A2H2) curves by double atrial extrastimulation (A1A2A3) has never been systematically studied. METHODS AND RESULTS This study was composed of 33 patients with typical AVNRT and continuous AVN conduction curves (group 1) and 103 patients with AVNRT and discontinuous AVN conduction curves (group 2). Using A1A2A3 with predefined fast pathway-conducted A2, we examined the effects of slow pathway ablation on the A2A3/A3H3 curves in both groups. In group 1, anterograde AVN effective refractory period (272+/-33 versus 277+/-47 ms, P>0.05) and AVN Wenckebach block cycle length (320+/-45 versus 343+/-59 ms, P>0.05) remained unchanged after ablation. A2H2max was shorter in group 1 than group 2 (237+/-89 versus 395+/-72 ms, P<0.05) at baseline. It shortened in group 2 (395+/-72 versus 221+/-78 ms, P<0.001) but remained unchanged in group 1 (237+/-89 versus 214+/-59 ms, P>0.05) after ablation. A1A2A3 could further disclose discontinuous A2A3/A3H3 curves in 29 patients of group 1. A3H3max shortened in both groups (375+/-81 versus 238+/-82 ms, P<0.001, and 419+/-104 versus 220+/-78 ms, P<0.001, respectively) in a similar fashion. Successful ablation resulted in loss of the left portion of the A2A3/A3H3 curves in the 4 patients of group 1 with continuous A2A3/A3H3 curves. CONCLUSIONS Use of A1A2A3 could expose discontinuous A2A3/A3H3 curves in most patients with continuous A1A2/A2H2 curves. Significant shortening of A3H3max after ablation may be indicative of successful elimination of AVNRT.

Functional polymorphisms of FGA, encoding α fibrinogen, are associated with susceptibility to venous thromboembolism in a Taiwanese population

To determine the genetic risk factors for venous thromboembolism (VTE), this study examined 14 genetic variants from 10 hemostatic genes in 186 Taiwanese VTE patients and the same number of matched controls, which demonstrated FGA (encoding α fibrinogen) Thr312Ala polymorphism was the only variant significantly associated with VTE. Nine genetic polymorphisms on the fibrinogen cluster region of chromosome 4q28 were further studied, in which four FGA polymorphisms were found in strong linkage disequilibrium and were significantly associated with VTE by genotype and allele frequency analyses. Haplotype analysis showed significantly different FGA haplotype frequencies between VTE patients and controls with the haplotype F1, containing -1051G, -3A, 312Ala and TaqI duplication alleles, significantly associated with susceptibility to VTE (P=0.001). Haplotype-pair analysis results also indicated a strong association of the haplotype-pair F1F1 with VTE in various VTE patient subgroups. In vitro functional analysis indicated that FGA -1051G, -3A and TaqI duplication alleles enhanced significantly the transcription level of FGA; however, control subjects with FGA genotypes containing these alleles had no elevated plasma fibrinogen levels. In conclusion, our experimental data indicated that functional genetic variants in FGA are risk factors for VTE in Taiwanese populations. Determination of FGA genotypes will likely contribute to primary prevention of this condition.

Atrioventricular nodal reentry tachycardia with multiple AH jumps: Electrophysiological characteristics and radiofrequency ablation

This article describes the additional use of incremental atrial burst pacing (A1A1) and double atrial extrastimulation with a predefined fast pathway conducted A2 (A1A2A3), rather than single atrial extrastimulation (A1A2) only, to characterize typical atrioventricular nodal reentrant tachycardia (AVNRT). The authors noted an additional 32% of patients had multiple anterograde AV nodal physiology demonstrated when A1A1 or A1A2A3 protocols were deployed compared to more conventional A1A2 protocols. The A2H2max (449 ± 147 vs 339 ± 94 ms) and A3H3max (481 ± 120 vs 389 ± 85 ms) were higher in 31 patients where multiple jumps in the AV nodal conduction curve were obtained (group 1) compared to 192 patients where only single jump was obtained (group 2) (both P < 0.01). Postablation, the degree of reduction of A2H2max (49%) and A3H3max (50%) in group 1 was greater than in group 2 (38% and 42%, respectively, P < 0.05). In seven of group 1 patients in whom A1A2A3 stimulation was required to reveal multiple jumps, the A2H2max remained unchanged after ablation (237 ± 89 vs 214 ± 59, P  > 0.05). A3H3max was the only parameter that shortened significantly after ablation. Generally, successful ablation resulted in loss of multiple discontinuities in A1A1/A1H1 or A2A3/A3H3 curves. In conclusion, a combination of A1A2, A1A1, and A1A2A3 are required to fully elucidate AVNRT. Significant shortening of AHmax or loss of multiple jumps after ablation indicates successful elimination of AVNRT in these patients. (PACE 2003; 26:1849–1855)

Exercise-induced myocardial ischaemia complicated by paroxysmal complete atrioventricular block

This study describes a case of exercise‐induced myocardial ischaemia accompanied by complete atrioventricular block (CAVB). A 59‐year‐old man with major depression, treated with regular imipramine and lithium for 20 years, experienced syncope episodes during exercise. Exercise, testing initially, identified ST depression in the inferior leads, and later found CAVB resulting in syncope and seizure. The patient recovered completely after resuscitation. Myocardial ischaemic markers were negative, but 35% stenosis was detected in the distal left main coronary artery by angiography. The combined use of verapamil, nitrate and aspirin was treated as the possible coronary spasm. Repeat treadmill caused negative ischaemic study or exercise‐induced arrhythmia, 7 days later. The pathophysiology of the very rare exercise‐induced paroxysmal CAVB has been reviewed.

Diagnostic use of metoclopramide in hypertension caused by pheochromocytoma

We studied 5-mg metoclopramide provocation in six pheochromocytomatous patients with different tumor locations, varying secretory patterns and large tumor sizes (> 12 g or equivalently) and in 14 patients with essential hypertension as part of diagnostic work-up, usually after screening with vanillylmandelic acid assay by the colorimetric method. Antihypertensive medication continued in three and five patients, respectively. Despite similar basal blood pressures patients with pheochromocytomas developed more prominent pressor responses in five of six patients than the nonpheochromocytomatous patients (P < 0.01), most (10) of the latter with negligible pressor responses. Basal plasma catecholamines were higher in each of the pheochromocytomatous patients of different secretory patterns. Further rises after provocation were seen in all pheochromocytomatous patients except one with early pressor response, and also in one nonpheochromocytomatous patient. All tests were well tolerated. Thus, we concluded that the metoclopramide test based upon joint pressor response and plasma catecholamine response can be safely used in the diagnosis of pheochromocytoma. A less stringent protocol including a short drug-off preparatory period may be a warranted compromise between feasibility and diagnostic accuracy.