ArticlePloS one2013
GSTCD and INTS12 regulation and expression in the human lung.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
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- Whole-genome association analyses of sleep-disordered breathing phenotypes in the NHLBI TOPMed program.Genome medicine · 2021Article
- Genome-Wide Association Study of Susceptibility to Idiopathic Pulmonary Fibrosis.American journal of respiratory and critical care medicine · 2020Article
- Defining a role for lung function associated gene GSTCD in cell homeostasis.Respiratory research · 2019Article
- Exposure to lipopolysaccharide (LPS) reduces contractile response of small airways from GSTCD-/- mice.PloS one · 2019Article
- The Overlap of Lung Tissue Transcriptome of Smoke Exposed Mice with Human Smoking and COPD.Scientific reports · 2018Article
- Integrator subunit 4 is a 'Symplekin-like' scaffold that associates with INTS9/11 to form the Integrator cleavage module.Nucleic acids research · 2018Article
- Meta-analysis of exome array data identifies six novel genetic loci for lung function.Wellcome open research · 2018Article
- Genetic variants associated with susceptibility to idiopathic pulmonary fibrosis in people of European ancestry: a genome-wide association study.The Lancet. Respiratory medicine · 2017Article
- Integrative Genomics of Emphysema-Associated Genes Reveals Potential Disease Biomarkers.American journal of respiratory cell and molecular biology · 2017Article
- Molecular basis for the interaction between Integrator subunits IntS9 and IntS11 and its functional importance.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Lung function associated gene Integrator Complex subunit 12 regulates protein synthesis pathways.BMC genomics · 2017Article
- Genome-wide association analyses for lung function and chronic obstructive pulmonary disease identify new loci and potential druggable targets.Nature genetics · 2017Article
- Cross-Cancer Genome-Wide Analysis of Lung, Ovary, Breast, Prostate, and Colorectal Cancer Reveals Novel Pleiotropic Associations.Cancer research · 2016Article
- Airway Epithelial Expression Quantitative Trait Loci Reveal Genes Underlying Asthma and Other Airway Diseases.American journal of respiratory cell and molecular biology · 2016Article
Corrections and comments
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Authors and funding
20 authors at 9 institutions in 5 countries.
Funding
Abstract
Genome-Wide Association Study (GWAS) meta-analyses have identified a strong association signal for lung function, which maps to a region on 4q24 containing two oppositely transcribed genes: glutathione S-transferase, C-terminal domain containing (GSTCD) and integrator complex subunit 12 (INTS12). Both genes were found to be expressed in a range of human airway cell types. The promoter regions and transcription start sites were determined in mRNA from human lung and a novel splice variant was identified for each gene. We obtained the following evidence for GSTCD and INTS12 co-regulation and expression: (i) correlated mRNA expression was observed both via Q-PCR and in a lung expression quantitative trait loci (eQTL) study, (ii) induction of both GSTCD and INTS12 mRNA expression in human airway smooth muscle cells was seen in response to TGFβ1, (iii) a lung eQTL study revealed that both GSTCD and INTS12 mRNA levels positively correlate with percent predicted FEV1, and (iv) FEV1 GWAS associated SNPs in 4q24 were found to act as an eQTL for INTS12 in a number of tissues. In fixed sections of human lung tissue, GSTCD protein expression was ubiquitous, whereas INTS12 expression was predominantly in epithelial cells and pneumocytes. During human fetal lung development, GSTCD protein expression was observed to be highest at the earlier pseudoglandular stage (10-12 weeks) compared with the later canalicular stage (17-19 weeks), whereas INTS12 expression levels did not alter throughout these stages. Knowledge of the transcriptional and translational regulation and expression of GSTCD and INTS12 provides important insights into the potential role of these genes in determining lung function. Future work is warranted to fully define the functions of INTS12 and GSTCD.
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