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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 FEV 1 , and (iv) FEV 1  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 .

GSTCD and INTS12 Regulation and Expression in the Human Lung