RESUMO
Process technologies have been developed for electron-beam (EB) lithography aimed at silicon quantum devices and their large-scale integration. It is necessary to understand the proximity effect and construct a method for its correction to perform EB lithography of fine and complicated structures. In this study, we investigate the lithography of Si quantum devices with a point-beam EB system and a maN 2401 negative tone resist, in order to correspond to various types of device structures. We optimize temperatures for specialized pre- and post-exposure bakes for forming â¼20 nm fine patterns with small line-edge roughness. Further, we demonstrated the fabrication of Si-on-insulator device patterns that have some tiny dots connected with many large wires/pads in the layout, with the careful tuning of the dose assignment. In this tuning, we used the EB process simulation to estimate the cumulative dose distribution effectively. In addition, we reproduced the experimentally obtained resist patterns via the EB process simulation after considering the mid-range effect, which is a factors in the proximity effect but is not yet deeply understood. The results of this study are expected to provide useful process technologies for EB lithography, which will help drastically accelerate the research on Si quantum devices with a high degree of freedom.
RESUMO
Recent genome-wide association studies have identified various dyslipidemia-related genetic variants. However, most studies were conducted in a cross-sectional manner. We thus performed longitudinal exome-wide association studies of dyslipidemia in a Japanese population. We used ~244,000 genetic variants and clinical data of 6022 Japanese individuals who had undergone annual health checkups for several years. After quality control, the association of dyslipidemia-related phenotypes with 24,691 single nucleotide polymorphisms (SNPs) was tested using the generalized estimating equation model. In total, 82 SNPs were significantly (Pâ¯<â¯2.03â¯×â¯10-6) associated with dyslipidemia phenotypes. Of these SNPs, four (rs74416240 of TCHP, rs925368 of GIT2, rs7969300 of ATXN2, and rs12231744 of NAA25) and two (rs34902660 of SLC17A3 and rs1042127 of CDSN) were identified as novel genetic determinants of hypo-HDL- and hyper-LDL-cholesterolemia, respectively. A replication study using the cross-sectional data of 8310 Japanese individuals showed the association of the six identified SNPs with dyslipidemia-related traits.
Assuntos
Dislipidemias/genética , Loci Gênicos , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Ataxina-2/genética , Proteínas de Transporte/genética , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Exoma , Feminino , Proteínas Ativadoras de GTPase/genética , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Japão , Masculino , Pessoa de Meia-Idade , Acetiltransferase N-Terminal B/genética , Proteínas Cotransportadoras de Sódio-Fosfato Tipo I/genéticaRESUMO
Recent genome-wide association studies identified genetic variants that confer susceptibility to type 2 diabetes mellitus (T2DM). However, few longitudinal genome-wide association studies of this metabolic disorder have been reported to date. Therefore, we performed a longitudinal exome-wide association study of T2DM, using 24,579 single nucleotide polymorphisms (SNPs) and repeated measurements from 6022 Japanese individuals. The generalized estimating equation model was applied to test relations of SNPs to three T2DM-related parameters: prevalence of T2DM, fasting plasma glucose level, and blood glycosylated hemoglobin content. Three SNPs that passed quality control were significantly (P<2.26×10-7) associated with two of the three T2DM-related parameters in additive and recessive models. Of the three SNPs, rs6414624 in EVC and rs78338345 in GGA3 were novel susceptibility loci for T2DM. In the present study, the SNP of GGA3 was predicted to be a genetic variant whose minor allele frequency has recently increased in East Asia.
Assuntos
Proteínas Adaptadoras de Transporte Vesicular/genética , Diabetes Mellitus Tipo 2/genética , Exoma/genética , Estudo de Associação Genômica Ampla , Proteínas/genética , Povo Asiático , Glicemia/metabolismo , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Hemoglobinas Glicadas/metabolismo , Humanos , Masculino , Proteínas de Membrana , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Recent genome-wide association studies have identified various genetic variants associated with hematological traits. Although it is possible that quantitative data of hematological traits are varied among the years examined, conventional genome-wide association studies have been conducted in a cross-sectional manner that measures traits at a single point in time. To address this issue, we have traced blood profiles in 4,884 Japanese individuals who underwent annual health check-ups for several years. In the present study, longitudinal exome-wide association studies were conducted to identify genetic variants related to 13 hematological phenotypes. The generalized estimating equation model showed that a total of 67 single nucleotide polymorphisms (SNPs) were significantly [false discovery rate (FDR) of <0.01] associated with hematological phenotypes. Of the 67 SNPs, nine SNPs were identified as novel hematological markers: rs4686683 of SENP2 for red blood cell count (FDR = 0.008, P = 5.5 × 10-6); rs3917688 of SELP for mean corpuscular volume (FDR = 0.005, P = 2.4 × 10-6); rs3133745 of C8orf37-AS1 for white blood cell count (FDR = 0.003, P = 1.3 × 10-6); rs13121954 at 4q31.2 for basophil count (FDR = 0.007, P = 3.1 × 10-5); rs7584099 at 2q22.3 (FDR = 2.6 × 10-5, P = 8.8 × 10-8), rs1579219 of HCG17 (FDR = 0.003, P = 2.0 × 10-5), and rs10757049 of DENND4C (FDR = 0.008, P = 5.6 × 10-5) for eosinophil count; rs12338 of CTSB for neutrophil count (FDR = 0.007, P = 2.9 × 10-5); and rs395967 of OSMR-AS1 for monocyte count (FDR = 0.008, P = 3.2 × 10-5).
Assuntos
Povo Asiático/genética , Fenômenos Fisiológicos Sanguíneos/genética , Loci Gênicos , Característica Quantitativa Herdável , Contagem de Eritrócitos , Eritrócitos/metabolismo , Exoma/genética , Feminino , Redes Reguladoras de Genes , Hematócrito , Hemoglobinas/metabolismo , Humanos , Japão , Contagem de Leucócitos , Desequilíbrio de Ligação/genética , MasculinoRESUMO
Recent genome-wide association studies have identified various obesity or metabolic syndrome (MetS) susceptibility loci. However, most studies were conducted in a cross-sectional manner. To address this gap, we performed a longitudinal exome-wide association study to identify susceptibility loci for obesity and MetS in a Japanese population. We traced clinical data of 6,022 Japanese subjects who had annual health check-ups for several years (mean follow-up period, 5 yr) and genotyped ~244,000 genetic variants. The association of single nucleotide polymorphisms (SNPs) with body mass index (BMI) or the prevalence of obesity and MetS was examined in a generalized estimating equation model. Our longitudinal exome-wide association studies detected 21 BMI- and five MetS-associated SNPs (false discovery rate, FDR <0.01). Among these SNPs, 16 have not been previously implicated as determinants of BMI or MetS. Cross-sectional data for obesity- and MetS-related phenotypes in 7,285 Japanese subjects were examined in a replication study. Among the 16 SNPs, three ( rs9491140 , rs145848316 , and rs7863248 ) were related to BMI in the replication cohort ( P < 0.05). In conclusion, three SNPs [ rs9491140 of NKAIN2 (FDR = 0.003, P = 1.9 × 10-5), rs145848316 of KMT2C (FDR = 0.007, P = 4.5 × 10-5), and rs7863248 of AGTPBP1 (FDR = 0.006, P = 4.2 × 10-5)] were newly identified as susceptibility loci for BMI.
Assuntos
Povo Asiático/genética , Índice de Massa Corporal , Loci Gênicos , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único/genética , Estudos de Coortes , Exoma/genética , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Síndrome Metabólica/genética , Pessoa de Meia-Idade , Obesidade/genética , Prevalência , Reprodutibilidade dos TestesRESUMO
Chronic kidney disease and hyperuricemia are serious global health problems. Recent genome-wide association studies have identified various genetic variants related to these disorders. However, most studies have been conducted in a cross-sectional manner. To identify novel susceptibility loci for chronic kidney disease or hyperuricemia, we performed longitudinal exome-wide association studies (EWASs), using ~ 244,000 genetic variants and clinical data of Japanese individuals who had undergone annual health checkups for several years. After establishing quality controls, the association of renal function-related traits in 5648 subjects (excluding patients with dialysis and population outliers) with 24,579 single nucleotide variants (SNVs) for three genetic models (P < 3.39 × 10- 7) was tested using generalized estimating equation models. The longitudinal EWASs revealed novel relations of five SNVs to renal function-related traits. Cross-sectional data for renal function-related traits in 7699 Japanese subjects were examined in a replication study. Among the five SNVs, rs55975541 in CDC42BPG was significantly (P < 4.90 × 10- 4) related to the serum concentration of uric acid in the replication cohort. We also examined the SNVs detected in our longitudinal EWASs with the information on P values in GKDGEN meta-analysis data. Four SNVs in SLC15A2 were significantly associated with the estimated glomerular filtration rate in European ancestry populations, although these SNVs were related to the serum concentration of uric acid with borderline significance in our longitudinal EWASs. Our findings indicate that CDC42BPG may be a novel susceptibility locus for hyperuricemia.
Assuntos
Predisposição Genética para Doença/genética , Hiperuricemia/genética , Polimorfismo de Nucleotídeo Único , Proteínas Serina-Treonina Quinases/genética , Povo Asiático/genética , Estudos de Coortes , Estudos Transversais , Feminino , Predisposição Genética para Doença/etnologia , Estudo de Associação Genômica Ampla/métodos , Taxa de Filtração Glomerular , Humanos , Hiperuricemia/sangue , Hiperuricemia/etnologia , Japão , Masculino , Pessoa de Meia-Idade , Ácido Úrico/sangueRESUMO
BACKGROUND AND AIM: We recently conducted a randomized placebo-controlled trial on the efficacy and safety of rikkunshito, a standardized Japanese herbal medicine, for the treatment of functional dyspepsia (FD). The present post-hoc study aimed to evaluate the differences in clinical characteristics between responders and non-responders among FD patients who received rikkunshito for 8 weeks. METHODS: Rikkunshito responders were defined by using a global patient assessment. Candidate predictors included age, gender, smoking, alcohol consumption, body mass index, comorbidity, Helicobacter pylori infection, plasma levels of acyl ghrelin and des-acyl ghrelin, severity of dyspeptic symptoms, FD subgroup, previous medication, and the type of recruiting institution (clinic or hospital). We calculated hazard ratios (HRs) by using Cox regression analysis with the factors that were indicated to be associated with responders. RESULTS: We assigned 83 and 42 patients to responder and non-responder categories, respectively. Lack of alcohol consumption (HR, 2.04; 95% confidence interval, 1.08-3.88) and low plasma des-acyl ghrelin levels (< 177 fmol/mL; HR, 2.42; 95% confidence interval, 1.24-4.73) were significantly associated with the efficacy of rikkunshito. Lack of alcohol consumption was associated with the efficacy of rikkunshito especially among H. pylori-infected participants. On the other hand, the low plasma des-acyl ghrelin was associated with the efficacy of rikkunshito especially among H. pylori-negative participants. CONCLUSIONS: A low baseline level of plasma des-acyl ghrelin was associated with an increased treatment efficacy of rikkunshito against FD. Lack of alcohol consumption was also clinically useful for predicting the response to rikkunshito.
Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Dispepsia/diagnóstico , Dispepsia/tratamento farmacológico , Grelina/sangue , Avaliação de Processos e Resultados em Cuidados de Saúde , Fitoterapia , Adulto , Idoso , Consumo de Bebidas Alcoólicas/efeitos adversos , Biomarcadores/sangue , Método Duplo-Cego , Medicamentos de Ervas Chinesas/administração & dosagem , Feminino , Infecções por Helicobacter , Helicobacter pylori , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
AIM: Various loci and genes that confer susceptibility to coronary artery disease (CAD) have been identified in Caucasian populations by genome-wide association studies (GWASs). The aim of the present study was to examine a possible association of chronic kidney disease (CKD) with 29 polymorphisms previously identified as susceptibility loci for CAD by meta-analyses of GWASs. METHODS: The study population comprised 2247 Japanese individuals, including 1588 subjects with CKD [estimated glomerular filtration rate (eGFR) of <60 mL min(-1) 1.73 m(-2) ] and 659 controls (eGFR of ≥90 mL min(-1) 1.73 m(-2) ). The genotypes for 29 polymorphisms of 28 candidate genes were determined. RESULTS: The χ(2) test revealed that rs4845625 (TâC) of IL6R, rs4773144 (AâG) of COL4A1, rs9319428 (GâA) of FLT1, and rs46522 (TâC) of UBE2Z were significantly (P < 0.05) related to CKD. Multivariable logistic regression analysis with adjustment for age, sex, body mass index, and the prevalence of smoking, hypertension, diabetes mellitus, and dyslipidaemia revealed that rs4845625 of IL6R (P = 0.0008; dominant model; odds ratio, 1.49), rs4773144 of COL4A1 (P = 0.0252; dominant model; odds ratio, 1.28), and rs9319428 of FLT1 (P = 0.0260: additive model; odds ratio, 0.77) were significantly associated with CKD. The serum concentration of creatinine was significantly (P = 0.0065) greater and eGFR was significantly (P = 0.0009) lower in individuals with the TC or CC genotype of IL6R than in those with the TT genotype. CONCLUSION: The rs4845625 of IL6R may be a susceptibility locus for CKD in Japanese individuals.
Assuntos
Povo Asiático/genética , Polimorfismo de Nucleotídeo Único , Receptores de Interleucina-6/genética , Insuficiência Renal Crônica/genética , Idoso , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Taxa de Filtração Glomerular/genética , Humanos , Japão/epidemiologia , Rim/fisiopatologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Fenótipo , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/etnologia , Insuficiência Renal Crônica/fisiopatologia , Fatores de RiscoRESUMO
BACKGROUND: Although genome-wide association studies (GWASs) have implicated several genes in the predisposition to chronic kidney disease (CKD) in Caucasian or African American populations, the genes that confer susceptibility to CKD in Asian populations remain to be identified definitively. We performed a GWAS to identify genetic variants that confer susceptibility to CKD in Japanese individuals. METHODS: 3851 Japanese individuals from three independent subject panels were examined. Subject panels A, B, and C comprised 252, 910, and 190 individuals with CKD and 249, 838, and 1412 controls, respectively. A GWAS for CKD was performed in subject panel A. RESULTS: Five single nucleotide polymorphisms (SNPs) at chromosome 3q28, ALPK1, FAM78B, and UMODL1 were significantly (false discovery rate<0.05) associated with CKD by the GWAS. The relation of these five SNPs and of an additional 22 SNPs at these loci to CKD was examined in subject panel B, revealing that rs9846911 at 3q28 was significantly associated with CKD in all individuals and that rs2074381 and rs2074380 in ALPK1 were associated with CKD in individuals with diabetes mellitus. These three SNPs were further examined in subject panel C, revealing that rs2074381 and rs2074380 were significantly associated with CKD. For subject panels B and C combined, rs9846911 was significantly associated with CKD in all individuals and rs2074381 and rs2074380 were associated with CKD in diabetic individuals. CONCLUSIONS: Chromosome 3q28 may be a susceptibility locus for CKD in Japanese individuals, and ALPK1 may be a susceptibility gene for CKD in such individuals with diabetes mellitus.
Assuntos
Povo Asiático/genética , Cromossomos Humanos Par 3/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Proteínas Quinases/genética , Insuficiência Renal Crônica/genética , Idoso , Idoso de 80 Anos ou mais , Complicações do Diabetes/genética , Diabetes Mellitus/genética , Feminino , Genótipo , Células HEK293 , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo ÚnicoRESUMO
BACKGROUND: The authors previously showed that the CâT polymorphism (rs6929846) of butyrophilin, subfamily 2, member A1 gene (BTN2A1) was significantly associated with myocardial infarction in Japanese individuals. Given that metabolic syndrome (MetS) is an important risk factor for myocardial infarction, the association of the rs6929846 of BTN2A1 with myocardial infarction might be attributable, at least in part, to its effect on susceptibility to MetS. AIM: The aim of the present study was to examine the relation of the rs6929846 of BTN2A1 to MetS in East Asian populations. METHODS: The study population comprised 5210 Japanese or Korean individuals (3982 individuals with MetS, 1228 controls) from three independent subject panels. Japanese subject panels A and B comprised 1322 individuals with MetS and 654 controls, and 1909 individuals with MetS and 170 controls, respectively, whereas the Korean population samples comprised 751 individuals with MetS and 404 controls. RESULTS: Comparison of genotype distributions using the χ(2) test revealed that the genotype distributions and allele frequencies of rs6929846 were significantly (p<0.05) associated with MetS in Japanese subject panels A (T allele frequency: MetS, 0.091; controls, 0.054; p=6.1×10(-5)) and B (T allele frequency: MetS, 0.091; controls, 0.039; p=0013) but not in the Korean population samples (T allele frequency: MetS, 0.102; controls, 0.125; p=0.0997). Multivariable logistic regression analysis with adjustment for covariates revealed that the rs6929846 of BTN2A1 was significantly (p<0.017) associated with MetS in Japanese subject panel A (p=0.0055, OR 1.97) and in all individuals (p=0.0038, OR 1.38), with the T allele representing a risk factor for this condition. CONCLUSION: BTN2A1 may be a susceptible gene for MetS in Japanese individuals.
Assuntos
Glicoproteínas de Membrana/genética , Síndrome Metabólica/genética , Polimorfismo de Nucleotídeo Único , Idoso , Alelos , Butirofilinas , Estudos de Casos e Controles , Análise Mutacional de DNA , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Japão/epidemiologia , Modelos Logísticos , Masculino , Síndrome Metabólica/etnologia , Pessoa de Meia-Idade , Mutação , Prevalência , República da Coreia/epidemiologia , Fatores de RiscoRESUMO
We propose and define a reservoir offset voltage as a voltage commonly applied to both reservoirs of a quantum dot and study the functions in p-channel Si quantum dots. By the reservoir offset voltage, the electrochemical potential of the quantum dot can be modulated. In addition, when quantum dots in different channels are capacitively coupled, the reservoir offset voltage of one of the QDs can work as a gate voltage for the others. Our results show that the technique will lead to reduction of the number of gate electrodes, which is advantageous for future qubit integration.
RESUMO
AIM: Although recent genetic studies suggested that several genetic variants increase the risk for chronic kidney disease (CKD), the genes that underlie genetic susceptibility to this condition remain to be identified definitively. We showed that the CâT polymorphism (rs6929846) of BTN2A1 and AâG polymorphism (rs2569512) of ILF3 were significantly associated with myocardial infarction in Japanese individuals by a genome-wide association study. The purpose of the present study was to examine a possible association of these polymorphisms (rs6929846, rs2569512) with CKD in Japanese individuals. METHODS: A total of 7542 Japanese individuals from two independent populations were examined: Subject panel A comprised 971 individuals with CKD (estimated glomerular filtration rate (eGFR) <60 mL/min 1.73 m(-2)) ) and 2269 controls (eGFR ≥60 mL/min 1.73 m(-2) ); and subject panel B comprised 1318 individuals with CKD and 2984 controls. RESULTS: The χ(2) test revealed that rs6929846 of BTN2A1, but not rs2569512 of ILF3, was significantly related to the prevalence of CKD both in subject panels A (P = 0.0383) and B (P = 0.0477). Multivariable logistic regression analysis with adjustment for covariates revealed that the CâT polymorphism (rs6929846) of BTN2A1 was significantly associated with the prevalence of CKD in subject panels A (P = 0.0422; recessive model; odds ratio, 2.36) and B (P = 0.0386; dominant model; odds ratio, 1.21) with the T allele representing a risk for this condition. CONCLUSION: Our results suggest that BTN2A1 may be a susceptibility gene for CKD in Japanese individuals.
Assuntos
Povo Asiático/genética , Taxa de Filtração Glomerular/genética , Nefropatias/genética , Rim/fisiopatologia , Glicoproteínas de Membrana/genética , Polimorfismo de Nucleotídeo Único , Idoso , Butirofilinas , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Doença Crônica , Feminino , Frequência do Gene , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Japão/epidemiologia , Nefropatias/etnologia , Nefropatias/fisiopatologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Proteínas do Fator Nuclear 90/genética , Razão de Chances , Fenótipo , Medição de Risco , Fatores de RiscoRESUMO
We demonstrate the measurement of p-channel silicon-on-insulator quantum dots at liquid helium temperatures by using a radio frequency (rf) reflectometry circuit comprising of two independently tunable GaAs varactors. This arrangement allows observing Coulomb diamonds at 4.2 K under nearly best matching condition and optimal signal-to-noise ratio. We also discuss the rf leakage induced by the presence of the large top gate in MOS nanostructures and its consequence on the efficiency of rf-reflectometry. These results open the way to fast and sensitive readout in multi-gate architectures, including multi qubit platforms.
RESUMO
The purpose of the present study was to identify genetic variants that confer susceptibility to chronic kidney disease (CKD) in Japanese individuals with metabolic syndrome. The study population comprised 2150 Japanese individuals with metabolic syndrome, including 411 subjects with CKD [estimated glomerular filtration rate (eGFR) <50 mL/min/1.73m(2)] and 1739 controls (eGFR >/=60 mL/min/1.73m(2)). The genotypes for 100 polymorphisms of 80 candidate genes were determined. The chi-square test, multivariable logistic regression analysis with adjustment for covariates, as well as a stepwise forward selection procedure revealed that nine polymorphisms of APOE, ABCA1, PTGS1, TNF, CPB2, AGTR1, OR13G1, and GNB3 were associated (P<0.05) with the prevalence of CKD. Among these polymorphisms, the -219G-->T polymorphism of APOE (rs405509) was most significantly associated with CKD in Japanese individuals with metabolic syndrome.
Assuntos
Apolipoproteínas E/genética , Povo Asiático/genética , Predisposição Genética para Doença , Síndrome Metabólica , Polimorfismo Genético , Insuficiência Renal Crônica , Idoso , Idoso de 80 Anos ou mais , Alelos , Feminino , Genótipo , Humanos , Modelos Logísticos , Masculino , Síndrome Metabólica/complicações , Síndrome Metabólica/etnologia , Síndrome Metabólica/genética , Pessoa de Meia-Idade , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/genéticaRESUMO
Chronic kidney disease (CKD) is a serious clinical condition that is associated with a high incidence of cardiovascular disease and end-stage renal disease. Although CKD has been recognised as a risk factor for myocardial infarction (MI), genetic factors for predisposition to MI in individuals with CKD have remained largely unknown. The purpose of the present study was to identify genetic variants that confer susceptibility to MI in Japanese individuals with CKD. The study subjects comprised 1,339 Japanese individuals with CKD, including 496 subjects with MI and 843 controls. The genotypes for 248 polymorphisms of 181 candidate genes were determined by a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. An initial screen of allele frequencies by the chi-square test revealed that the 11496G-->A (Arg353Gln) polymorphism of F7 (rs6046) was significantly (false discovery rate <0.05) associated with the prevalence of MI in individuals with CKD. Subsequent multivariable logistic regression analysis with adjustment for covariates and a stepwise forward selection procedure also revealed that this polymorphism was significantly (p <0.005) associated with MI, with the variant A (Gln) allele protecting against this condition. Determination of genotype for the 11496G-->A (Arg353Gln) polymorphism of F7 may prove informative for assessment of the genetic risk for MI in individuals with CKD.
Assuntos
Povo Asiático/genética , Fator VII/genética , Nefropatias/genética , Infarto do Miocárdio/genética , Polimorfismo de Nucleotídeo Único , Idoso , Estudos de Casos e Controles , Doença Crônica , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Japão , Nefropatias/complicações , Nefropatias/etnologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/etnologia , Razão de Chances , Medição de Risco , Fatores de RiscoRESUMO
AIMS: The aim of this study was to evaluate the role of matrix metalloproteinases (MMPs) for the prediction of long-term maintenance of sinus rhythm (SR) after cardioversion in atrial fibrillation (AF). METHODS AND RESULTS: The study comprised 102 patients with AF. Pharmacological cardioversion was attempted for a 4-week period with anti-arrhythmic drugs in all patients. Those who failed medication underwent electrical cardioversion. Blood samples for biomarkers and echocardiographic data were obtained at baseline. Thirty-four patients (33.3%) converted to SR by pharmacological (n = 22) and electrical (n = 12) cardioversion and maintained it (SR group). The remaining 68 patients were refractory to the AF (RAF) group including recurrence (n = 22) and unsuccessful treatment (n = 46) after electrical/pharmacological cardioversion. Refractory AF was significantly associated with the duration of AF, hypertension, left atrial diameter, brain natriuretic peptide, MMP-2, and tissue inhibitor of MMP-2. For both multivariable logistic regression analysis and stepwise forward selection procedure, the duration of AF >5 months [odds ratio (OR) 15.32] and MMP-2 >767.0 ng/mL (OR 4.84) were significantly associated with RAF. CONCLUSION: Our study suggests that elevated MMP-2 and longer AF duration increased the risk for difficulty in restoring SR in AF patients. Stratification of subjects according to the MMP-2 level may therefore be important for the effective management of AF.
Assuntos
Antiarrítmicos/uso terapêutico , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/terapia , Cardioversão Elétrica , Metaloproteinase 2 da Matriz/sangue , Avaliação de Resultados em Cuidados de Saúde/métodos , Fibrilação Atrial/sangue , Humanos , Japão/epidemiologia , Estudos Longitudinais , Prognóstico , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Resultado do TratamentoRESUMO
Although diabetes mellitus has been recognized as a risk factor for chronic kidney disease (CKD), genetic factors for predisposition to CKD in individuals with diabetes mellitus remain elucidated. The purpose of the present study was to identify genetic variants that confer susceptibility to CKD among individuals with type 2 diabetes mellitus. The study population comprised 1742 Japanese individuals, including 636 subjects with CKD [estimated glomerular filtration rate (eGFR)<60 ml/min/1.73 m2] and 1106 controls (eGFR>or=60 ml/min/1.73 m2). The genotypes for 24 polymorphisms of 22 candidate genes were determined. An initial screen of allele frequencies by the Chi-square test revealed that four polymorphisms were significantly (false discovery rate<0.05) associated with the prevalence of CKD in individuals with type 2 diabetes mellitus. Subsequent multivariable logistic regression analysis with adjustment for covariates as well as a stepwise forward selection procedure revealed that the 8733T-->C polymorphism of ALOX5AP (rs3803278), the C-->T (Ser532Leu) polymorphism of IRAK1 (rs1059703), and the 2445G-->A (Ala54Thr) polymorphism of FABP2 (rs1799883) were significantly (P<0.05) associated with the prevalence of CKD. Our results suggest that ALOX5AP, IRAK1, and FABP2 are susceptibility loci for CKD among Japanese individuals with type 2 diabetes mellitus.
Assuntos
Diabetes Mellitus Tipo 2/complicações , Predisposição Genética para Doença/genética , Falência Renal Crônica/genética , Polimorfismo Genético , Proteínas Ativadoras de 5-Lipoxigenase , Idoso , Povo Asiático/genética , Proteínas de Transporte/genética , Proteínas de Ligação a Ácido Graxo/genética , Feminino , Frequência do Gene , Variação Genética , Genótipo , Humanos , Quinases Associadas a Receptores de Interleucina-1/genética , Japão , Falência Renal Crônica/complicações , Falência Renal Crônica/etnologia , Modelos Logísticos , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo ÚnicoRESUMO
The purpose of the present study was to identify genetic variants that confer susceptibility to chronic kidney disease (CKD) in individuals with low or high serum concentrations of triglycerides (TG), high-density lipoprotein (HDL)-cholesterol, or low-density lipoprotein (LDL)-cholesterol, thereby contributing to the personalized prevention of CKD in such individuals. The study population comprised 5944 Japanese individuals, including 1706 subjects with CKD [estimated glomerular filtration rate (eGFR)<60 ml/min/1.73 m2] and 4238 controls (eGFR>or=60 ml/min/1.73 m2). The genotypes for 296 polymorphisms of 202 candidate genes were determined. The Chi-square test, multivariable logistic regression analysis with adjustment for covariates, and a stepwise forward selection procedure revealed that seven different polymorphisms were significantly (P<0.005) associated with the prevalence of CKD in individuals with low or high serum concentrations of TG or HDL- or LDL-cholesterol: the Aright curved arrow G (Glu23Lys) polymorphism of KCNJ11 and the 125592Cright curved arrow A (Thr431Asn) polymorphism of ROCK2 in individuals with low serum TG; the 734Cright curved arrow T (Thr254Ile) polymorphism of ACAT2 and the Cright curved arrow G (Gln27Glu) polymorphism of ADRB2 in individuals with high serum TG; the -1607/1Gright curved arrow 2G polymorphism of MMP1 in individuals with low serum HDL-cholesterol; the Gright curved arrow A (Val158Met) polymorphism of COMT in individuals with low serum LDL-cholesterol; the 584Gright curved arrow A (Gln192Arg) polymorphism of PON1 in individuals with high serum LDL-cholesterol. No polymorphism was associated with CKD in individuals with high serum HDL-cholesterol. These results suggest that polymorphisms associated with CKD may differ among individuals with different lipid profiles. Stratification of subjects according to lipid profiles may thus be important for personalized prevention of CKD based on genetic information.
Assuntos
Predisposição Genética para Doença/genética , Falência Renal Crônica/sangue , Falência Renal Crônica/genética , Lipídeos/sangue , Polimorfismo Genético , Transportador 1 de Cassete de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/genética , Idoso , Arildialquilfosfatase/genética , Distribuição de Qui-Quadrado , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Frequência do Gene , Variação Genética , Genótipo , Humanos , Modelos Logísticos , Masculino , Metaloproteinase 1 da Matriz/genética , Pessoa de Meia-Idade , Análise Multivariada , Canais de Potássio Corretores do Fluxo de Internalização/genética , Triglicerídeos/sangue , Quinases Associadas a rho/genéticaRESUMO
The purpose of the present study was to identify genetic variants which confer susceptibility to chronic kidney disease (CKD) in high- or low-risk subjects defined by conventional risk factors separately. The study population comprised 2828 Japanese individuals, including 434 subjects with CKD [estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2)] and 2394 controls (eGFR > or =60 ml/min/ 1.73 m(2)). The 1012 high-risk subjects had both hypertension and diabetes mellitus, and the 1816 low-risk subjects had none of these conditions. The genotypes for 296 polymorphisms of 202 candidate genes were determined. The Chi-square test, multivariable logistic regression analysis with adjustment for covariates, as well as a stepwise forward selection procedure revealed that ten different polymorphisms were associated (P<0.05) with the prevalence of CKD in high- or low-risk subjects: the -519Aright curved arrow G polymorphism of MMP1, the 1061Aright curved arrow G (Ile405Val) polymorphism of CETP, the Aright curved arrow G (Lys45Glu) polymorphism of MMP3, the -219Gright curved arrow T polymorphism of APOE, the Aright curved arrow G (Ile1205Val) polymorphism of COL3A1, the -863Cright curved arrow A polymorphism of TNF, and the 1454Cright curved arrow G (Leu125Val) polymorphism of PECAM1 in high-risk subjects; and the 1167Cright curved arrow T (Asn389Asn) polymorphism of TGFBR2, the 2386Aright curved arrow G (Ile796Val) polymorphism of SCAP, and the TAAAright curved arrow del polymorphism of PDE4D in low-risk subjects. Among these polymorphisms, the -519Aright curved arrow G polymorphism of MMP1 and the 1167Cright curved arrow T (Asn389Asn) polymorphism of TGFBR2 were most significantly associated with CKD in high- or low-risk individuals, respectively. These results suggest that polymorphisms associated with CKD may differ among high- or low-risk subjects. Stratification of subjects according to conventional risk factors may thus be important for personalized prevention of CKD based on genetic information.
Assuntos
Nefropatias/epidemiologia , Nefropatias/genética , Polimorfismo Genético/genética , Idoso , Apolipoproteínas E/genética , Povo Asiático , Proteínas de Transferência de Ésteres de Colesterol/genética , Colágeno Tipo III/genética , Nucleotídeo Cíclico Fosfodiesterase do Tipo 3/genética , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4 , Feminino , Frequência do Gene , Predisposição Genética para Doença/genética , Genótipo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Masculino , Metaloproteinase 1 da Matriz/genética , Metaloproteinase 3 da Matriz/genética , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Molécula-1 de Adesão Celular Endotelial a Plaquetas/genética , Proteínas Serina-Treonina Quinases/genética , Receptor do Fator de Crescimento Transformador beta Tipo II , Receptores de Fatores de Crescimento Transformadores beta/genética , Fatores de RiscoRESUMO
The aim of the present study was to identify gene polymorphisms that confer susceptibility to obesity. A total of 5448 unrelated Japanese individuals from two independent populations were examined: subject panel A comprised 4252 individuals who visited participating hospitals; subject panel B comprised 1196 community-dwelling elderly individuals. The genotypes for 95 polymorphisms of 67 candidate genes were determined. The chi(2) test revealed that six polymorphisms were related (p<0.05) to the prevalence of obesity in subject panel A; after application of Bonferroni's correction, however, only the 2677G --> A/T polymorphism (rs2032582) of the ATP-binding cassette, subfamily B, member 1 gene (ABCB1) was significantly associated (p=0.0003) with obesity. Subsequent multivariable logistic regression analysis also revealed that the 2677G --> A/T polymorphism of ABCB1 was significantly associated with obesity. For validation of this association, the 2677G --> A/T polymorphism of ABCB1 was examined in subject panel B and again found to be significantly associated with obesity. Body mass index was significantly (p=0.01) greater for individuals with the variant T allele of this polymorphism than for those with the GG genotype in the combined subject panels A and B. Our results suggest that the ABCB1 genotype may prove informative for assessment of genetic risk for obesity in Japanese individuals.