PubMed Health⌕ Search

Biomedical subjects

Shiro Kamakura

Publications and source records attributed to Shiro Kamakura.

At least 19 recordsLinked to original sources
PubMed2006

Diagnostic and prognostic value of a type 1 Brugada electrocardiogram at higher (third or second) V1 to V2 recording in men with Brugada syndrome.

To evaluate the diagnostic and prognostic value of an electrocardiogram (ECG) recorded at a higher (third or second) intercostal space, 98 men (17 to 76 years of age, mean +/- SD 47 +/- 13; with documented ventricular fibrillation [VF] in 22 and syncope in 32) were categorized into 3 groups; 68 men had a spontaneous type 1 ECG in standard leads V(1) and V(2) (S group), 19 had a spontaneous type 1 ECG only in the higher V(1) and V(2) leads (H group), and 11 had a type 1 ECG only after receiving class Ic sodium channel blockers (Ic group). There were no significant differences in baseline clinical characteristics, including VF episodes, syncope, atrial fibrillation, family history, late potentials, and inducibility of VF during electrophysiologic study across the 3 groups. During prospective follow-up periods (779 +/- 525, 442 +/- 282, and 573 +/- 382 days, respectively), subsequent cardiac events occurred in 11 men (16%) within the S group, in 2 men (11%) in the H group, and in 0 men (0%) in the Ic group (p = NS, S vs H group). In men with previous episodes of VF, subsequent cardiac events occurred in 7 (44%) within the S group and in 2 (50%) in the H group (p = NS). In conclusion, men with a spontaneous type 1 Brugada ECG recorded only at higher leads V(1) and V(2) showed a prognosis similar to that of men with a type 1 ECG in using standard leads V(1) and V(2).

Adolescent↗
PubMed2006

"Left-variant" atypical atrioventricular nodal reentrant tachycardia: electrophysiological characteristics and effect of slow pathway ablation within coronary sinus.

INTRODUCTION: Recent anatomical and electrophysiological studies have demonstrated the presence of leftward posterior nodal extension (LPNE); however, its role in the genesis of atrioventricular nodal reentrant tachycardia (AVNRT) is poorly understood. This study was performed to characterize successful slow pathway (SP) ablation site and to elucidate the role of LPNE in genesis of atypical AVNRT with eccentric activation patterns within the coronary sinus (CS). METHODS AND RESULTS: Among 45 patients with atypical AVNRT (slow-slow/fast-slow/both = 20/22/3 patients) with concentric (n = 37, 82%) or eccentric CS activation (n = 8, 18%), successful ablation site was evaluated. Among 35/37 patients (95%) with concentric CS activation, ablation at the conventional SP region outside CS eliminated both retrograde SP conduction and AVNRT inducibility. Among eight patients with eccentric CS activation, the earliest retrograde atrial activation was found at proximal CS 16 +/- 4 mm distal to the ostium during AVNRT. The earliest retrograde activation site was located at inferior to inferoseptal mitral annulus, consistent with the presumed location of LPNE. Ablation at the conventional SP region with electroanatomical approach only rendered AVNRT nonsustained without elimination of retrograde SP conduction in seven of eight patients (88%). Ablation targeted to the earliest retrograde atrial activation site within proximal CS (15 +/- 4 mm distal to the ostium); however, eliminated retrograde SP conduction and rendered AVNRT noninducible in six of eight patients (75%). CONCLUSION: In 75% of "left-variant" atypical AVNRT, ablation within proximal CS was required to eliminate eccentric retrograde SP conduction and render AVNRT noninducible, suggesting LPNE formed retrograde limb of reentrant circuit.

Adult↗
PubMed2006

Unique electrophysiologic characteristics of atrioventricular nodal reentrant tachycardia with different ventriculoatrial block patterns: effects of slow pathway ablation and insights into the location of the reentrant circuit.

BACKGROUND: The electrophysiologic mechanisms of different ventriculoatrial (VA) block patterns during atrioventricular nodal reentrant tachycardia (AVNRT) are poorly understood. OBJECTIVES: The purpose of this study was to characterize AVNRTs with different VA block patterns and to assess the effects of slow pathway ablation. METHODS: Electrophysiologic data from six AVNRT patients with different VA block patterns were reviewed. RESULTS: All AVNRTs were induced after a sudden AH "jump-up" with the earliest retrograde atrial activation at the right superoparaseptum. Different VA block patterns comprised Wenckebach His-atrial (HA) block (n = 4), 2:1 HA block (n = 1), and variable HA conduction times during fixed AVNRT cycle length (CL) (n = 1). Wenckebach HA block during AVNRT was preceded by gradual HA interval prolongation with fixed His-His (HH) interval and unchanged atrial activation sequence. AVNRT with 2:1 HA block was induced after slow pathway ablation for slow-slow AVNRT with 1:1 HA conduction, and earliest atrial activation shifted from right inferoparaseptum to superoparaseptum without change in AVNRT CL. The presence of a lower common pathway was suggested by a longer HA interval during ventricular pacing at AVNRT CL than during AVNRT (n = 5) or Wenckebach HA block during ventricular pacing at AVNRT CL (n = 1). In four patients, HA interval during ventricular pacing at AVNRT CL was unusually long (188 +/- 30 ms). Ablations at the right inferoparaseptum rendered AVNRT noninducible in 5 (83%) of 6 patients. CONCLUSION: Most AVNRTs with different VA block patterns were amenable to classic slow pathway ablation. The reentrant circuit could be contained within a functionally protected region around the AV node and posterior nodal extensions, and different VA block patterns resulted from variable conduction at tissues extrinsic to the reentrant circuit.

Adolescent↗
PubMed2006

Assessment of ability of activation mapping by duodecapolar catheter to diagnose complete isthmus block utilizing electroanatomical mapping system.

UNLABELLED: Duodecapolar catheters (DPCs) have been widely used to diagnose isthmus block after ablation in patients with atrial flutters. The purpose of this study was to assess the ability of DPC to diagnose isthmus block utilizing electroanatomical mapping system (CARTO). METHODS: Sixty-two patients with common atrial flutter underwent isthmus ablation during CS pacing while DPC was positioned at lateral wall of RA along tricuspid annulus (TA). When activation sequence of DPC recording changed exclusively counter-clockwise after ablation, or did not even after ablations targeting single potentials on ablation line (Ab-L), only lateral side of Ab-L was remapped using CARTO to assess whether complete block (CB) was established. RESULTS: After ablation, DPC recording suggested CB and incomplete block (ICB) in 53 (85%) and 9 patients (15%), respectively. In 51/53 patients (96%) with CB suggested by DPC recordings, CARTO remap also demonstrated CB, however, in the remaining two patients (4%), demonstrated ICB with residual isthmus conduction that was slow enough to allow wavefront conducting around TA to arrive at distal dipole of DPC earlier, mimicking CB. In 4/9 patients (44%) with ICB suggested by DPC recordings, CARTO remap also demonstrated ICB, however, in the remaining five patients (56%), demonstrated CB with earlier arrival of wavefront traversing posterior wall at just lateral to Ab-L than that conducting around TA, mimicking ICB. Sensitivity, specificity, positive, and negative predictive values of DPC to diagnose CB were 91, 67, 96, and 44%, respectively. CONCLUSIONS: Mapping using DPC would not be sufficient for diagnosis of CB and ICB.

Aged↗
PubMed2006

Common sodium channel promoter haplotype in asian subjects underlies variability in cardiac conduction.

BACKGROUND: Reduced cardiac sodium current slows conduction and renders the heart susceptible to ventricular fibrillation. Loss of function mutations in SCN5A, encoding the cardiac sodium channel, are one cause of the Brugada syndrome, associated with slow conduction and a high incidence of ventricular fibrillation, especially in Asians. In this study, we tested the hypothesis that an SCN5A promoter polymorphism common in Asians modulates variability in cardiac conduction. METHODS AND RESULTS: Resequencing 2.8 kb of SCN5A promoter identified a haplotype variant consisting of 6 polymorphisms in near-complete linkage disequilibrium that occurred at an allele frequency of 22% in Asian subjects and was absent in whites and blacks. Reporter activity of this variant haplotype, designated HapB, in cardiomyocytes was reduced 62% compared with wild-type haplotype (P=0.006). The relationship between SCN5A promoter haplotype and PR and QRS durations, indexes of conduction velocity, was then analyzed in a cohort of 71 Japanese Brugada syndrome subjects without SCN5A mutations and in 102 Japanese control subjects. In both groups, PR and QRS durations were significantly longer in HapB individuals (P< or =0.002) with a gene-dose effect. In addition, up to 28% and 48% of variability in PR and QRS durations, respectively, were attributable to this haplotype. The extent of QRS widening during challenge with sodium channel blockers, known to be arrhythmogenic in Brugada syndrome and other settings, was also genotype dependent (P=0.002). CONCLUSIONS: These data demonstrate that genetically determined variable sodium channel transcription occurs in the human heart and is associated with variable conduction velocity, an important contributor to arrhythmia susceptibility.

Adolescent↗
PubMed2006

Prevention of life-threatening ventricular tachyarrhythmia by a novel and pure class-III agent, nifekalant hydrochloride.

Nifekalant hydrochloride (NIF) is a novel intravenous class-III antiarrhythmic agent with a pirimidinedione structure that purely blocks the K+ channel without inhibiting beta-adrenergic receptors. The authors investigated the efficacy of NIF for refractory ventricular tachycardia/fibrillation (VT/VF). They studied 30 patients treated with an intravenous infusion of NIF [ 26 men, 4 women; age: 63 +/- 17 (mean +/- SD) years] at a dose of 0.19 +/- 0.14 mg/kg body weight per hour. Sixteen were patients with acute coronary syndrome (ACS), and 14 were patients with chronic structural heart disease (Chr-HD). Amiodarone and sotalol had already been administered to 9 patients with Chr-HD before the administration of NIF. The QT and T peak-end (Tp-e) intervals were measured and corrected by Bazett's method (QTc, cTp-e). The left ventricular ejection fraction was depressed (28 +/- 9%). NIF was effective for preventing VT/VF without proarrhythmia and hemodynamic deterioration in 21 patients (70%; 12 with ACS; 9 with Chr-HD), but ineffective in 4 patients (all with Chr-HD). The QTc prolongation in the responders was more pronounced than in the nonresponders (25% +/- 15% versus 5% +/- 7% increase; P < 0.05). Proarrhythmic torsade de pointes (TdP) developed transiently in the remaining 5 patients in whom the cTp-e was markedly increased compared with that in the responders (93% +/- 49% versus 37% +/- 41% increase; P < 0.05). In conclusion, these findings indicate that the intravenous administration of NIF is useful in the emergent treatment of inhibiting drug-refractory VT/VF, although proarrhythmic TdP owing to an enhancement of transmural dispersion of repolarization needs to be taken into account.

Aged↗
PubMed2006

Electrical space-time abnormalities of ventricular depolarization in patients with Brugada syndrome and patients with complete right-bundle branch blocks studied by magnetocardiography.

BACKGROUND: Both ventricular depolarization abnormalities (QRS complex) and repolarization ones (ST/T) are still controversial in literature. The objective of this study was to clarify the space-time variations that occur in patients carriers of Brugada syndrome using Magnetocardiography and also compare them with cases of complete right-bundle branch block (CRBBB) and individuals without any dromotropic disorder (control group). METHODS AND RESULTS: Magnetocardiograms (MCGs) of Brugada syndrome patients (n = 16), CRBBB patients (n = 14), and members of a control group (n = 46) at rest were recorded. The MCGs were used to produce a whole-heart electrical-activation diagram (W-HEAD), which can visualize the spatial time-variant activation in the whole heart. In the W-HEAD pattern, three activations were located in the left ventricle, and CRBBB patients had a wide peak with about 65-ms delay on the right anterior side. While the Brugada syndrome pattern has a posteromedian left-ventricle excitation, that is half the amplitude that occurs in CRBBB patients, the electrical conduction rate to the posterosuperior septum area was low. CONCLUSIONS: The W-HEAD data made it possible to visualize space-time depolarization abnormalities. These findings suggest that the electrical conduction rate to the posterosuperior septum area in Brugada syndrome cases is low, and this low activation may be a feature of typical Brugada syndrome.

Adult↗
PubMed2006

Site-specific influence of transversal conduction across crista terminalis on recognition of isthmus block.

BACKGROUND: Transversal conduction across crista terminalis (CT) is commonly observed during low-rate coronary sinus (CS) pacing after isthmus ablation and sometimes mimics incomplete clockwise isthmus block (IB). Site-specific influence of trans-cristal conduction gap on recognition of clockwise IB has been poorly understood. METHODS: Forty-five patients with common-type atrial flutter underwent mapping of CT and free wall lateral to CT during CS pacing of 100 ppm using CARTO after verification of IB, while duodecapolar catheter was positioned along tricuspid annulus to map periannular activation. RESULTS: A total of 43 gaps were demonstrated at upper (n = 15, 35%), middle (n = 17, 40%), and lower one-thirds of CT (n = 11, 25%) in 36 of 45 patients (80%). Gaps were single in 31 (69%) and multiple in 5 patients (11%). Activation patterns of free wall lateral to CT in CARTO maps were descending pattern without gaps (n = 9, 20%), collision pattern with a single gap (n = 31, 69%), and simultaneous pattern with multiple gaps (n = 5, 11%). Activation sequence of duodecapolar catheter was complete block pattern in 41 (91%) and incomplete block pattern in 4 patients (9%), masquerading as persistent clockwise isthmus conduction. The incomplete block pattern in duodecapolar catheter was exclusively associated with a gap at the lower CT (0/15, 0/17, and 4/11 gaps at upper, middle, and lower CT, respectively; P < 0.01) and was attributable to faster conduction across CT gaps than in complete block pattern. CONCLUSIONS: Trans-cristal conduction was commonly observed during low-rate CS pacing. Rapid transversal conduction exclusively across lower CT masqueraded as incomplete clockwise IB.

Atrial Flutter↗
PubMed2006

Pilsicainide-induced verapamil sensitive idiopathic left ventricular tachycardia.

A 20-year-old man was admitted to our hospital for treatment of verapamil sensitive idiopathic left ventricular tachycardia (ILVT). During the electrophysiologic study (EPS), no sustained ventricular tachycardia (VT) could be induced both at baseline and after infusion of isoproterenol. However, sustained clinical VT could be easily induced with single ventricular extrastimulation following intravenous administration of pilsicainide, a class Ic sodium channel blocker. The arrhythmia was ablated with radiofrequency catheter ablation.

Adult↗
PubMed2006

Spatial distribution of repolarization and depolarization abnormalities evaluated by body surface potential mapping in patients with Brugada syndrome.

BACKGROUND: Mutations in sodium channel gene, SCN5A, have been identified in Brugada syndrome, but it is still unclear as to how sodium channel dysfunction relates to arrhythmogenesis. We examined spatial distribution of both repolarization and depolarization abnormalities in patients with Brugada syndrome by using 87-leads body surface potential mapping (BSPM). METHODS: BSPM was recorded under baseline condition and after pharmacological interventions in 28 patients with Brugada syndrome (27 males, 49 +/- 14 years). The ST-segment amplitude 20 ms after the end of QRS (ST20), QRS duration, and corrected recovery time (RTc) were measured in all 87-leads, and averaged among 6-leads (D-F, 5-6) reflecting right ventricular outflow tract (RVOT) potentials and the other 81-leads. RESULTS: The ST20 was elevated at baseline, normalized by isoproterenol, and augmented by pilsicainide in only the RVOT. The RTc was longer at baseline and increased by pilsicainide in only the RVOT. On the other hand, the QRS duration was slightly widened at baseline, further increased by pilsicainide, but not changed by isoproterenol in both leads. CONCLUSIONS: The ST-segment elevation and the RTc prolongation were localized and modulated by agents only in the RVOT region, while the slight QRS widening at baseline and further increase by pilsicainide were observed homogeneously. Our data suggest that depolarization abnormalities are distributed homogeneously, whereas repolarization abnormalities are localized in the RVOT.

Adolescent↗
PubMed2006

Magnetocardiography study on ventricular depolarization-current pattern in patients with brugada syndrome and complete right-bundle branch blocks.

BACKGROUND: The objective of this study is to use magnetocardiography to determine the existence of a small abnormal current during ventricular depolarization in patients with Brugada syndrome. To understand this small difference in abnormal current during ventricular depolarization, we compared abnormal currents of patients with cases of complete right-bundle-branch block (CRBBB). METHODS AND RESULTS: We developed a whole-heart electrical bull's eye map (WHEBEM) that uses magnetocardiograms (MCGs) to visualize the current distribution in a circular map. MCGs of Brugada syndrome patients (n = 16), CRBBB patients (n = 10), and controls (n = 12) at rest were recorded. In the WHEBEMs of Brugada syndrome patients, the magnitude of the S-wave current in the upper-right direction of the anterior side is larger than that of the controls. In addition, the R-wave current direction is similar to that of the controls, and the R-wave vector is distributed over a larger area than that of the controls. On the other hand, the CRBBB patients have a distribution of R-wave currents over a larger area in the left anteromedian region and the left posteromedian region. Moreover, in all CRBBB patients, S-wave currents with a large magnitude have the same direction distributed over a small area. CONCLUSIONS: The WHEBEM findings suggest that there is an abnormal current in the direction to the upper right (in the S-wave) in the anterosuperior region of Brugada syndrome patients. We thus conclude that a WHEBEM has the potential to detect characteristics of heart disease.

Adolescent↗
PubMed2006

Catheter ablation of stable and unstable ventricular tachycardias in patients with arrhythmogenic right ventricular dysplasia.

INTRODUCTION: A reentrant circuit within an area of abnormal myocardium is suspected as the origin of ventricular tachycardia (VT) in patients with arrhythmogenic right ventricular dysplasia (ARVD). OBJECTIVES: To examine the relationship between the reentrant circuits of VT and the abnormal electrograms in ARVD, and to assess the feasibility of a block line formation in the reentrant circuit isthmus utilizing electroanatomical mapping system (CARTO) guidance. METHODS AND RESULTS: An electrophysiological study and catheter ablation (CA) were performed in 17 ARVD patients (13 men, 47 +/- 17 year) using CARTO. Endocardial mapping during sinus rhythm demonstrated electrogram abnormalities extended from the tricuspid annulus (TA) or the right ventricular outflow tract in 16 of 17 patients. In 13 hemodynamically stable VTs, the reentrant circuits and critical slow conduction sites for the CA were investigated during VTs. The entire macro-reentrant pathway was identified in 6/13 stable VTs (figure-of-8 in 4, single loop in 2). In the remaining seven VTs, a focal activation pattern was found in four and an unidentifiable pattern in three. CA successfully abolished all the macro-reentrant and focal tachycardias, however, not effective in three unidentifiable VTs. In the 13 cases with unstable VT, the linear conduction block zone was produced between the sites with abnormal electrograms and the TA. Ultimately, 23/26 VTs (88%) became noninducible after the CA. During follow-up (26 +/- 15 months), 13/17 patients remained free from any VT episodes. CONCLUSIONS: CARTO is useful for characterizing the anatomical and electrophysiological substrates, and for identifying the optimal ablation sites for VT associated with ARVD.

Adult↗
PubMed2006

Randomized study of angiotensin II type 1 receptor blocker vs dihydropiridine calcium antagonist for the treatment of paroxysmal atrial fibrillation in patients with hypertension.

BACKGROUND: Mega trials of rhythm vs rate control could not demonstrate the usefulness of available antiarrhythmic drugs, so a more effective and safer therapy for atrial fibrillation (AF) is now required. One candidate is the so-called "upstream therapy", which refers to the blockade of upstream modifying elements (renin - angiotensin system, cathecholamines, oxidative stress etc) that contribute to the arrhythmogenic substrate. METHODS AND RESULTS: The Japanese Rhythm Management Trial II for Atrial Fibrillation (J-RHYTHM II study) is a randomized comparative evaluation of an angiotensin II type 1 blocker (candesartan) and a dihydropiridine calcium blocker (amlodipine), both combined with antithrombotic therapy, as an antiarrhythmic therapy for the treatment of paroxysmal AF (PAF) associated with hypertension. To test the usefulness of this therapy, this study will reveal the recurrence rate of asymptomatic as well as symptomatic PAF during 1-year of treatment with candesartan or amlodipine, using daily transtelephonic monitoring. CONCLUSIONS: The J-RHYTHM II study will follow 400 patients with PAF and hypertension who were treated at approximately 50 sites throughout Japan, and will provide clinically important information.

Amlodipine↗
PubMed2006

Long-term follow-up of transvenous defibrillation leads: high incidence of fracture in coaxial polyurethane lead.

BACKGROUND: As a result of longer follow-up after implantation of cardioverter defibrillators (ICD), fatigue of the leads has become a concern. The aim of this study was to determine the incidence and clinical presentation of ICD lead failures. METHODS AND RESULTS: The study population consisted of 241 patients with 249 ICD leads who underwent implantation of an ICD with a transvenous lead system. After device implantation, the patients were routinely followed up every 4 months. Five lead failures (2.0%) occurred as an oversensing of artifact during the follow-up period (2.6+/-2.1 years); 4 of those 5 patients received inappropriate shocks and 1 case of lead failure was identified in a patient with frequent episodes of non-sustained ventricular fibrillation. In particular, the right ventricular polyurethane transvenous lead in the Medtronic model 6936 failed in 4 (13%) of 31 cases. Percutaneous lead extraction was not available in all cases, so an additional ICD lead was inserted through the same site of the subclavian vein. CONCLUSIONS: Lead failures may occur 5 years after ICD implantation and polyurethane leads have an especially high incidence of failure. However, there were no follow-up parameters observed that predicted lead failures.

Adult↗
PubMed2006

Heart failure elevates serum levels of cibenzoline in arrhythmic patients.

BACKGROUND: Cibenzoline dosing is generally based on renal function, but serum concentrations might be greater than the expected therapeutic levels when standard oral dosing is used. Because heart failure might modify cibenzoline pharmacokinetics, the difference in cibenzoline pharmacokinetics between patients with and without heart failure was evaluated. METHODS AND RESULTS: The study enrolled 368 patients (233 men, 135 women) that had been hospitalized and received cibenzoline therapy at the National Cardiovascular Center from January 2001 to May 2005. There were 89 patients with heart failure (51 men, 38 women) and 279 patients without heart failure (182 men, 97 women). They had therapeutic drug monitoring > or = 3 days after the beginning of treatment with cibenzoline. Brain natriuretic peptide (BNP) was measured in 81 patients (50 men, 31 women) concurrently with therapeutic drug monitoring of cibenzoline. The difference in serum cibenzoline concentration/(dose/weight) (C/D) values between patients with and without heart failure was analyzed using analysis of covariance (ANCOVA) with creatinine clearance (Ccr) serving as the covariate. The effects of dose/weight and the log-transformed BNP (log-BNP) values on serum cibenzoline concentrations were also assessed using ANCOVA. There were 135 and 361 measurements of serum cibenzoline concentration in patients with and without heart failure, respectively. Pearson's correlation coefficient analyses in the patients with and without heart failure revealed that the C/D values were significantly correlated with Ccr (with heart failure, y = -0.837x + 169, r = -0.211, p = 0.014; without heart failure, y = -0.789x + 132, r = -0.393, p < 0.001), and the ANCOVA model indicated that C/D values were significantly higher in patients with heart failure than without heart failure. The ANCOVA model also showed that dose/weight, Ccr and the log-BNP value were significant factors. CONCLUSIONS: The selection of a cibenzoline dose based only on renal function may increase the risk of toxicity in patients with heart failure. Cardiac function should be taken into account in cibenzoline dosing. The log-BNP may be a useful index for predicting serum cibenzoline concentrations.

Adult↗
PubMed2006

Sequence-based analysis of the CYP2D6*36-CYP2D6*10 tandem-type arrangement, a major CYP2D6*10 haplotype in the Japanese population.

The frequency of the CYP2D6*10 allele (100C>T) in the Japanese is relatively high (0.3-0.4), and the two *10-related genes, Ch1 (currently *10B) and Ch2 (*36), and their tandem arrangement Ch(2)-Ch(1) (*36-*10B) have been reported. Although the tandem form of *36-*10 is assumed to be a major form, no detailed information has been reported for its intervening and flanking regions. Thus in this study, the tandem-type *36-*10B and the single-type *10 were analyzed by long-range PCR and sequencing of the subsequent nested PCR products. The sequence of the entire *36-*10 region confirmed the recombination of CYP2D6*10 with CYP2D7P. Also, we found that most of the *10B-harboring haplotypes have the upstream *36 gene and that the majority of the remaining haplotypes are the single-type *10B. Haplotype frequencies of the single-type *10 and *36-*10B were 0.06 and 0.30, respectively, in the subjects analyzed. Additionally, several novel single nucleotide polymorphisms (SNPs) were found in the *36 region and several *36 haplotypes were identified. This sequence information is an important addition to the CYP2D6 sequence data that was obtained by the human genome project.

3' Flanking Region↗
PubMed2006

Diverse structures of chimeric CYP-REP7/6-containing CYP2D6 and a novel defective CYP2D6 haplotype harboring single-type *36 and CYP-REP7/6 in Japanese.

Chimeric REP7/6 has been used as a marker of CYP2D6 deletion, such as for CYP2D6*5. However, the CYP2D6*10D (*10D) haplotype found in a Japanese population consist of CYP2D6*10B, CYP2D7P-derived 3'-flanking region, and a chimeric repetitive sequence, CYP-REP7/6 (REP7/6) (Ishiguro et al. Clin. Chim. Acta. 2004: 347, 217-221). From our analysis, REP7/6 was found in 26 out of 254 Japanese subjects. Thus, the REP7/6-containing CYP2D6 genes (2D6-REP7/6) were analyzed in detail. In order to specifically detect the 2D6-REP7/6 structure, primers were designed in CYP2D6 intron 6 and the REP7/6 3'-flanking region. Among 26 subjects analyzed by PCR, 5 had 2D6-REP7/6. The other 21 subjects were confirmed to have *5 by another *5-specific primer set. Three out of five subjects with 2D6-REP7/6 had the *10D structure. However, further analysis by PCR and sequencing revealed that their haplotypes were further divided into tandem-type *36-*10D (n=2) and single-type *10D (n=1). The remaining two subjects had a novel type of a *36-containing defective structure that consists of CYP2D6*36 and 3'-flanking REP7/6 (single-type *36-REP7/6). Then, REP7/6 sequences in *5, *10D, *36-*10D, and single-type *36 were determined and classified into 5 types: types A to D for *5, type E for *10D and *36-*10D, and type F for *36. These findings could be useful for accurate determination of *5 and REP7/6-harboring aberrant CYP2D6 haplotypes.

Asian People↗