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Background  Genome-wide association studies (GWASs) of a large cohort of subjects with chronic obstructive pulmonary disease (COPD) have successfully identified multiple risk genes, including fibroblast growth factor 7 ( FGF7 ). However, the underlying molecular mechanism influencing function of FGF7 and risk of COPD remains further study.    Methods  In this study, we replicated the genetic association of variants near the  FGF7  gene in 258 Chinese Han patients with COPD and 311 healthy controls. Additionally, we functionally evaluated a candidate causal variant upstream of the FGF7 gene.    Results  The most significant association was observed at rs12905203 ( P  = 5.9 × 10 − 3 , odd ratio, OR = 1.516) that explains associations of previously reported variants at the  FGF7  locus. Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation-quantitative polymerase chain reaction (ChIP-qPCR) assays showed that the risk allele of the variant was bound to activator protein 1 transcription factors (c-Fos and c-Jun) with a significantly reduced affinity and associated with decreased mRNA expression of  FGF7  in fibroblast cells at both resting and PMA/Ionomycin-stimulated conditions. Overexpression of c-Fos and c-Jun proteins or stimulation with PMA/Ionomycin significantly increases mRNA expression of  FGF7  in fibroblast cells. Bioinformatic analysis showed that the variant overlaps with multiple genetic regulatory marks, suggesting the regulatory DNA element might function as an enhancer for the  FGF7  gene. Luciferase enhancer activity assays demonstrated that the DNA sequences carrying the variant produce enhancer activity while the risk allele of the variant reduces its activity.    Conclusions  In this study, we demonstrated a consistent association of the  FGF7  gene with COPD and mechanistically characterized a candidate functional variant upstream of the  FGF7  gene. These data highlighted the important role of the risk variant and the  FGF7  gene in influencing risk for COPD.    Electronic supplementary material  The online version of this article (10.1186/s12881-019-0761-7) contains supplementary material, which is available to authorized users.

A functional variant alters binding of activating protein 1 regulating expression of FGF7 gene associated with chronic obstructive pulmonary disease