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Joseph T. Glessner - One of the best experts on this subject based on the ideXlab platform.
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genome wide investigation of schizophrenia associated plasma ndel1 Enzyme Activity
Schizophrenia Research, 2016Co-Authors: Ary Gadelha, Camila M. Yonamine, Jonathan R. I. Coleman, Gerome Breen, Diego Robles Mazzoti, Renata Pellegrino, Vanessa Kiyomi Ota, Sintia Iole Belangero, Joseph T. GlessnerAbstract:Ndel1 is a DISC1-interacting oligopeptidase that cleaves in vitro neuropeptides as neurotensin and bradykinin, and which has been associated with both neuronal migration and neurite outgrowth. We previously reported that plasma Ndel1 Enzyme Activity is lower in patients with schizophrenia (SCZ) compared to healthy controls (HCs). To our knowledge, no previous study has investigated the genetic factors associated with the plasma Ndel1 Enzyme Activity. In the current analyses, samples from 83 SCZ patients and 92 control subjects that were assayed for plasma Ndel1 Enzyme Activity were genotyped on Illumina Omni Express arrays. A genetic relationship matrix using genome-wide information was then used for ancestry correction, and association statistics were calculated genome-wide. Ndel1 Enzyme Activity was significantly lower in patients with SCZ (t=4.9; p<0.001) and was found to be associated with CAMK1D, MAGI2, CCDC25, and GABGR3, at a level of suggestive significance (p<10(-6)), independent of the clinical status. Then, we performed a model to investigate the observed differences for case/control measures. 2 SNPs at region 1p22.2 reached the p<10(-7) level. ZFPM2 and MAD1L1 were the only two genes with more than one hit at 10(-6) order of p value. Therefore, Ndel1 Enzyme Activity is a complex trait influenced by many different genetic variants that may contribute to SCZ physiopathology.
Gerome Breen - One of the best experts on this subject based on the ideXlab platform.
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genome wide investigation of schizophrenia associated plasma ndel1 Enzyme Activity
Schizophrenia Research, 2016Co-Authors: Ary Gadelha, Camila M. Yonamine, Jonathan R. I. Coleman, Gerome Breen, Diego Robles Mazzoti, Renata Pellegrino, Vanessa Kiyomi Ota, Sintia Iole Belangero, Joseph T. GlessnerAbstract:Ndel1 is a DISC1-interacting oligopeptidase that cleaves in vitro neuropeptides as neurotensin and bradykinin, and which has been associated with both neuronal migration and neurite outgrowth. We previously reported that plasma Ndel1 Enzyme Activity is lower in patients with schizophrenia (SCZ) compared to healthy controls (HCs). To our knowledge, no previous study has investigated the genetic factors associated with the plasma Ndel1 Enzyme Activity. In the current analyses, samples from 83 SCZ patients and 92 control subjects that were assayed for plasma Ndel1 Enzyme Activity were genotyped on Illumina Omni Express arrays. A genetic relationship matrix using genome-wide information was then used for ancestry correction, and association statistics were calculated genome-wide. Ndel1 Enzyme Activity was significantly lower in patients with SCZ (t=4.9; p<0.001) and was found to be associated with CAMK1D, MAGI2, CCDC25, and GABGR3, at a level of suggestive significance (p<10(-6)), independent of the clinical status. Then, we performed a model to investigate the observed differences for case/control measures. 2 SNPs at region 1p22.2 reached the p<10(-7) level. ZFPM2 and MAD1L1 were the only two genes with more than one hit at 10(-6) order of p value. Therefore, Ndel1 Enzyme Activity is a complex trait influenced by many different genetic variants that may contribute to SCZ physiopathology.
Elena Garciamartin - One of the best experts on this subject based on the ideXlab platform.
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cyp3a4 variant alleles in white individuals with low cyp3a4 Enzyme Activity
Clinical Pharmacology & Therapeutics, 2002Co-Authors: Elena Garciamartin, Carmen Martinez, Rosa M Pizarro, F J GarciagamitoAbstract:Objective Our objective was to evaluate the presence of CYP3A4 gene variants in white individualswith low CYP3A4 Enzyme Activity. Methods Persons with extremely low Enzyme Activity, either in vitro or in vivo, were selected in a panel of 97 healthy subjects. Genetic analyses for CYP3A4 variant alleles present in white subjects, including CYP3A4*1B, CYP3A4*2, CYP3A4*4, CYP3A4*5, CYP3A4*6, CYP3A4*8, CYP3A4*11, CYP3A4*12, and CYP3A4*13, were performed on genomic deoxyribonucleic acid from these subjects by amplification-restriction and sequencing. Results With the exception of CYP3A4*1B, none of the variant alleles analyzed were present in30 genes from persons with extremely low Enzyme Activity. CYP3A4*1B was present in the population studied with an allele frequency of 5.5%. Nevertheless, the presence of CYP3A4*1B does not correlate with low Enzyme Activity, either in vivo or in vitro, in either heterozygosity or homozygosity. CYP3A4*2 was not identified in 290 genes from Spanish persons or in 70 genes from Finnish persons. Conclusions Although the genetic component of the interindividual variability of CYP3A4 Enzyme Activity seems to be high, our findings do not support a key role for the variant alleles analyzed on the majority of white persons with low CYP3A4 Activity. This suggests the occurrence of as yet unknown mutations that affect CYP3A4 orother functionally related genes. Clinical Pharmacology & Therapeutics (2002) 71, 196–204; doi: 10.1067/mcp.2002.121371
David E Kelley - One of the best experts on this subject based on the ideXlab platform.
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skeletal muscle lipid content and oxidative Enzyme Activity in relation to muscle fiber type in type 2 diabetes and obesity
Diabetes, 2001Co-Authors: Jing He, Simon C Watkins, David E KelleyAbstract:In obesity and type 2 diabetes, skeletal muscle has been observed to have a reduced oxidative Enzyme Activity, increased glycolytic Activity, and increased lipid content. These metabolic characteristics are related to insulin resistance of skeletal muscle and are factors potentially related to muscle fiber type. The current study was undertaken to examine the interactions of muscle fiber type in relation to oxidative Enzyme Activity, glycolytic Enzyme Activity, and muscle lipid content in obese and type 2 diabetic subjects compared with lean healthy volunteers. The method of single-fiber analysis was used on vastus lateralis muscle obtained by percutaneous biopsy from 22 lean, 20 obese, and 20 type 2 diabetic subjects (ages 35 ± 1, 42 ± 2, and 52 ± 2 years, respectively), with values for BMI that were similar in obese and diabetic subjects (23.7 ± 0.7, 33.2 ± 0.8, and 31.8 ± 0.8 kg/m 2 , respectively). Oxidative Enzyme Activity followed the order of type I > type IIa > type IIb, but within each fiber type, skeletal muscle from obese and type 2 diabetic subjects had lower oxidative Enzyme Activity than muscle from lean subjects ( P P
Ary Gadelha - One of the best experts on this subject based on the ideXlab platform.
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genome wide investigation of schizophrenia associated plasma ndel1 Enzyme Activity
Schizophrenia Research, 2016Co-Authors: Ary Gadelha, Camila M. Yonamine, Jonathan R. I. Coleman, Gerome Breen, Diego Robles Mazzoti, Renata Pellegrino, Vanessa Kiyomi Ota, Sintia Iole Belangero, Joseph T. GlessnerAbstract:Ndel1 is a DISC1-interacting oligopeptidase that cleaves in vitro neuropeptides as neurotensin and bradykinin, and which has been associated with both neuronal migration and neurite outgrowth. We previously reported that plasma Ndel1 Enzyme Activity is lower in patients with schizophrenia (SCZ) compared to healthy controls (HCs). To our knowledge, no previous study has investigated the genetic factors associated with the plasma Ndel1 Enzyme Activity. In the current analyses, samples from 83 SCZ patients and 92 control subjects that were assayed for plasma Ndel1 Enzyme Activity were genotyped on Illumina Omni Express arrays. A genetic relationship matrix using genome-wide information was then used for ancestry correction, and association statistics were calculated genome-wide. Ndel1 Enzyme Activity was significantly lower in patients with SCZ (t=4.9; p<0.001) and was found to be associated with CAMK1D, MAGI2, CCDC25, and GABGR3, at a level of suggestive significance (p<10(-6)), independent of the clinical status. Then, we performed a model to investigate the observed differences for case/control measures. 2 SNPs at region 1p22.2 reached the p<10(-7) level. ZFPM2 and MAD1L1 were the only two genes with more than one hit at 10(-6) order of p value. Therefore, Ndel1 Enzyme Activity is a complex trait influenced by many different genetic variants that may contribute to SCZ physiopathology.