Abstract:
:Background: Although there is evidence that the CYP3A4*22 variant should be considered in tacrolimus dosing in renal transplantation, its impact beyond tacrolimus dose requirements remains controversial. Methods: In a cohort of 121 kidney transplant recipients, we analyzed the CYP3A4*1B, CYP3A4*22, and CYP3A5*3 alleles and the ABCB1 variants 1236C>T, 2677G>T/A, and 3435C>T for their impact on exposure and dose requirement. Relevant clinical outcome measures such as acute rejection within the first year after transplantation, delayed graft function, and renal function at discharge (estimated glomerular filtration rate) were evaluated. Results: Extensive metabolizer (n = 17, CYP3A4*1/*1 carriers with at least one CYP3A5*1 allele) showed significantly higher tacrolimus dose requirement (P = 0.004) compared with both intermediate metabolizer (IM, n = 93, CYP3A5*3/*3 plus CYP3A4*1/*1 or CYP3A4*22 carriers plus one CYP3A5*1 allele), and poor metabolizer (n = 11, CYP3A4*22 allele in combination with CYP3A5*3/*3) after onset of therapy. Significantly higher dose requirement was observed in CYP3A5 expressers (P = 0.046) compared with non-expressers again at onset of therapy. Using the log additive genetic model, the area under the curve for the total observation period up to 16 days was significantly associated with the CYP3A5*3 genotype (P = 3.34 × 10-4) as well as with the IM or extensive metabolizer phenotype (P = 1.54 × 10-4), even after adjustment for multiple testing. Heterozygous carriers for CYP3A4*22 showed significantly higher areas under the curve than the CYP3A4*1/*1 genotype in the second week post-transplantation (adjusted P = 0.016). Regarding clinical outcomes, acute rejection was significantly associated with human leukocyte antigen mismatch (≥3 alleles; OR = 12.14, 95% CI 1.76, 525.21, P = 0.019 after correction for multiple testing). Graft recipients from deceased donors showed higher incidende of delayed graft function (OR 7.15, 95% CI 2.23, 30.46, adjusted P = 0.0008) and a lower estimated glomerular filtration rate at discharge (P = 0.0001). Tested CYP3A4 or CYP3A5 variants did not show any effects on clinical outcome parameters. ABCB1 variants did neither impact on pharmacokinetics nor on clinical endpoints. Conclusion: At our transplantation center, both CYP3A5*3 and, to a lesser extent, CYP3A4*22 affect tacrolimus pharmacokinetics early after onset of therapy with consequences for steady-state treatment in routine clinical practice.
journal_name
Front Genetjournal_title
Frontiers in geneticsauthors
Abdel-Kahaar E,Winter S,Tremmel R,Schaeffeler E,Olbricht CJ,Wieland E,Schwab M,Shipkova M,Jaeger SUdoi
10.3389/fgene.2019.00871subject
Has Abstractpub_date
2019-09-26 00:00:00pages
871issn
1664-8021journal_volume
10pub_type
杂志文章abstract::Different genes have their protein products localized in various subcellular compartments. The diversity in protein localization may serve as a gene characteristic, revealing gene essentiality from a subcellular perspective. To measure this diversity, we introduced a Subcellular Diversity Index (SDI) based on the Gene...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2019.01342
更新日期:2020-01-21 00:00:00
abstract::Primary ciliary dyskinesia (PCD), a rare genetic disorder, is mostly caused by defects in more than 40 known cilia structure-related genes. However, in approximately 20-35% of patients, it is caused by unknown genetic factors, and the inherited pathogenic factors are difficult to confirm. Kartagener syndrome (KTS) is ...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2019.00749
更新日期:2019-08-22 00:00:00
abstract::For the past several decades, research in understanding the molecular basis of human muscle aging has progressed significantly. However, the development of accessible tissue-specific biomarkers of human muscle aging that may be measured to evaluate the effectiveness of therapeutic interventions is still a major challe...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2018.00242
更新日期:2018-07-12 00:00:00
abstract::mRNA-Seq is a precise and highly reproducible technique for measurement of transcripts levels and yields sequence information of a transcriptome at a single nucleotide base-level thus enabling us to determine splice junctions and alternative splicing events with high confidence. Often analysis of mRNA-Seq data does no...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2012.00239
更新日期:2012-11-27 00:00:00
abstract::There is evidence of a purifying filter acting in the female germline to prevent the expansion of deleterious mutations in the mitochondrial DNA (mtDNA). Given our poor understanding of this filter, here we investigate the competence of the mouse embryo to eliminate dysfunctional mitochondria. Toward that, mitochondri...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2020.00762
更新日期:2020-07-15 00:00:00
abstract::Pacu (Piaractus mesopotamicus) is a Neotropical fish of major importance for South American aquaculture. Septicemia caused by Aeromonas hydrophila bacteria is currently considered a substantial threat for pacu aquaculture that have provoked infectious disease outbreaks with high economic losses. The understanding of m...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2020.00604
更新日期:2020-06-09 00:00:00
abstract::The fragile X premutation (PM) allele contains a CGG expansion of 55-200 repeats in the FMR1 gene's promoter. Male PM carriers have an elevated risk of developing neurological and psychiatric changes, including an approximately 50% risk of the fragile X-associated tremor/ataxia syndrome (FXTAS). The aim of this study ...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2018.00531
更新日期:2018-11-12 00:00:00
abstract::Anther extrusion (AE) is the most important male floral trait for hybrid wheat seed production. AE is a complex quantitative trait that is difficult to phenotype reliably in field experiments not only due to high genotype-by-environment effects but also due to the short expression window in the field condition. In thi...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2020.586687
更新日期:2020-12-08 00:00:00
abstract::The prevalence of obesity continues to increase particularly in developed countries. To establish the primary mechanisms involved, relevant animal models which track the developmental pathway to obesity are required. This need is emphasized by the substantial rise in the number of overweight and obese children, of whi...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2011.00024
更新日期:2011-05-31 00:00:00
abstract::Ubiquitination is a reversible protein modification broadly implicated in cellular functions. Signaling processes mediated by ubiquitin (ub) are crucial for the cellular response to DNA double-strand breaks (DSBs), one of the most dangerous types of DNA lesions. In particular, the DSB response critically relies on act...
journal_title:Frontiers in genetics
pub_type: 杂志文章,评审
doi:10.3389/fgene.2015.00282
更新日期:2015-09-08 00:00:00
abstract::Communication disorders have complex genetic origins, with constellations of relevant gene markers that vary across individuals. Some genetic variants are present in healthy individuals as well as those affected by developmental disorders. Growing evidence suggests that some variants may increase susceptibility to the...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2015.00272
更新日期:2015-08-24 00:00:00
abstract::Classification of DNA sequences is an important issue in the bioinformatics study, yet most existing methods for phylogenetic analysis including Multiple Sequence Alignment (MSA) are time-consuming and computationally expensive. The alignment-free methods are popular nowadays, whereas the manual intervention in those ...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2019.00234
更新日期:2019-04-09 00:00:00
abstract::Poultry feed constitutes the largest cost in poultry production, estimated to be up to 70% of the total cost. Moreover, there is pressure on the poultry industry to increase production to meet the protein demand of humans and simultaneously reduce emissions to protect the environment. Therefore, improving feed efficie...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2020.00243
更新日期:2020-04-03 00:00:00
abstract::Hematopoiesis results in the correct formation of all the different blood cell types. In mammals, it starts from specific hematopoietic stem and precursor cells residing in the bone marrow. Mature blood cells are responsible for supplying oxygen to every cell of the organism and for the protection against pathogens. T...
journal_title:Frontiers in genetics
pub_type: 杂志文章,评审
doi:10.3389/fgene.2018.00348
更新日期:2018-08-31 00:00:00
abstract::Germline variants of PIP4K2A impact susceptibility of acute lymphoblastic leukemia (ALL) through inducing its overexpression. Although limited reports suggested the oncogenic role of PIP4K2A in cancers, regulatory network and prognostic effect of this gene remains poorly understood in tumorigenesis and leukemogenesis....
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2018.00721
更新日期:2019-01-15 00:00:00
abstract::The tropical Andes are a hotspot of biodiversity, but detailed altitudinal and latitudinal distribution patterns of species are poorly understood. We compare the distribution and diversity patterns of four Andean plant groups on the basis of georeferenced specimen data: the genus Nasa (Loasaceae), the two South Americ...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2014.00351
更新日期:2014-10-10 00:00:00
abstract::Late blight of potato (Solanum tuberosum L.) caused by the oomycete Phytophthora infestans (Mont.) de Bary, is one of the most important bottlenecks of potato production worldwide. Cultivars with high levels of durable, race unspecific, quantitative resistance are part of a solution to this problem. However, breeding ...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2015.00294
更新日期:2015-09-23 00:00:00
abstract::Long noncoding RNAs (lncRNAs) are a novel class of RNA molecules defined as transcripts longer than 200 nucleotides that lack protein coding potential. They constitute a major, but still poorly characterized part of human transcriptome, however, evidence is growing that they are important regulatory molecules involved...
journal_title:Frontiers in genetics
pub_type: 杂志文章,评审
doi:10.3389/fgene.2015.00145
更新日期:2015-04-23 00:00:00
abstract:BACKGROUND:Non-synonymous single-nucleotide polymorphisms (nsSNPs) within the coding regions of genes causing amino acid substitutions (AASs) may have a large impact on protein function. The possibilities to identify nsSNPs across genomes have increased notably with the advent of next-generation sequencing technologies...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2013.00021
更新日期:2013-03-06 00:00:00
abstract::Lung diseases impact patients across the lifespan, from infants in the first minutes of life through the aged population. Congenital abnormalities of lung structure can cause lung disease at birth or make adults more susceptible to chronic disease. Continuous inhalation of atmospheric components also requires the lung...
journal_title:Frontiers in genetics
pub_type: 杂志文章,评审
doi:10.3389/fgene.2018.00517
更新日期:2018-10-31 00:00:00
abstract::The concept of Developmental Origins of Health and Diseases (DOHaD) recognizes that an unfavorable maternal environment alters the developmental trajectory of the fetus and can lead to long-term risk of developing chronic noncommunicable diseases. More recently, the concept of a paternal transmission [Paternal Origins...
journal_title:Frontiers in genetics
pub_type: 杂志文章,评审
doi:10.3389/fgene.2019.00337
更新日期:2019-04-18 00:00:00
abstract::The SLC2A9 gene, that encodes a renal uric acid reuptake transporter, has genetic variants that explain ∼3% of variance in urate levels. There are previous reports of non-additive interaction between SLC2A9 genotype and environmental factors which influence urate control. Therefore, our aim was to further investigate ...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2015.00313
更新日期:2015-10-14 00:00:00
abstract::Long intergenic non-coding RNAs (lincRNAs) are an abundant and functionally diverse class of eukaryotic transcripts. Reported lincRNA repertoires in mammals vary, but are commonly in the thousands to tens of thousands of transcripts, covering ~90% of the genome. In addition to elucidating function, there is particular...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2017.00052
更新日期:2017-05-09 00:00:00
abstract::The ability to sense and respond to stressful conditions is essential to maintain organismal homeostasis. It has long been recognized that stress response factors that improve survival in changing conditions can also influence longevity. In this review, we discuss different strategies used by animals in response to de...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2012.00257
更新日期:2012-11-27 00:00:00
abstract::Retinoblastoma (Rb) is a primary intraocular malignant tumor that occurs primarily in children, and results from loss-of-function mutations in the RB transcriptional corepressor 1 (RB1) gene. Genetic testing forms the basis of genetic counseling for affected families, as well as for clinical management of this disease...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2020.00142
更新日期:2020-03-11 00:00:00
abstract::Hox genes are major regulators of embryonic development. One of their most conserved functions is to coordinate the formation of specific body structures along the anterior-posterior (AP) axis in Bilateria. This architectural role was at the basis of several morphological innovations across bilaterian evolution. In th...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2015.00267
更新日期:2015-08-18 00:00:00
abstract::A biochemical activity, that is, enzymatic reaction or molecular interaction, frequently involves a molecule, for example, an enzyme, capable of interacting with numerous substrates or partners. Specificity is a fundamental property of biochemical activities, and relative specificity refers to the situation whereby a ...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2011.00065
更新日期:2011-09-20 00:00:00
abstract::In this study, we examined whether smoking and drinking affect sperm quality and the DNA methylation of the repetitive element LINE-1, MEST, P16, H19, and GNAS in sperm. Semen samples were obtained from 143 male residents in a minority-inhabited district of Guizhou province in southwest China. Quantitative DNA methyla...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2019.01001
更新日期:2019-10-18 00:00:00
abstract::Genetic variants can influence the expression of mRNA and protein. Genetic regulatory loci such as expression quantitative trait loci (eQTLs) and protein quantitative trait loci (pQTLs) exist in several species. However, it remains unclear how human genetic variants regulate mRNA and protein expression. Here, we chara...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2019.00806
更新日期:2019-09-10 00:00:00
abstract::Selection for improved host response to infectious disease offers a desirable alternative to chemical treatment but has proven difficult in practice, due to low heritability estimates of disease traits. Disease data from field studies is often binary, indicating whether an individual has become infected or not followi...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2012.00215
更新日期:2012-10-22 00:00:00