Association of CTGF polymorphisms with idiopathic pulmonary fibrosis

Cellular and molecular mechanisms (English)

Dymph Klay
St Antonius ziekenhuis, ILD expertisecentrum
Connective tissue growth factor (CTGF) is a profibrotic mediator and expressed by fibroblasts and type alveolar epithelial cells. CTGF has been found to be upregulated in bronchoalveolar lavage cells, fibroblasts, plasma and tissue of idiopathic pulmonary fibrosis (IPF) patients. Two polymorphisms in the CTGF gene (rs6918698, rs9399005) have already been investigated in systemic sclerosis patients and controls. Both polymorphisms may alter transcription of the CTGF gene.In this study we investigated whether the risk allele of these two polymorphisms and two other CTGF polymorphisms (rs125261 and rs940237) with an association in hepatic fibrosis, chon’s disease and diabetic patients, predisposes to idiopathic pulmonary fibrosis (IPF).
Method: 342 IPF patients, of which 140 with familial interstitial pneumonia (FIP) (n=123 index) and sex-matched healthy controls (n=296) were genotyped for CTGF rs6918698, rs9399005, rs125261 and rs940237.
Results: Comparison of cases with healthy controls showed a significant allelic association of CTGF rs6918698 with sporadic IPF (p=0,03) and FIP (p=0,001). The association with FIP was only found in patients with a telomerase related mutation (p=0,005) and FIP with unknown cause (0,02) and not in FIP with a surfactant mutation. In addition, the allele frequency of CTGF rs9399005C was significantly higher inFIP compared to controls (p=0,001). This association was only observed in FIP with a telomerase related mutation (p=p=0,002). Dividing the IPF patients in two groups based on working or consensus diagnosis showed an significant allelic association of CTGF rs6918698 with both groups; working (p=0,004) and consensus diagnosis (p=0,04). For rs9399005, only an association was found with IPF patients with a consensus diagnosis (p=0,02). For CTGF rs940237 and rs125261 no significant allelic associations were observed.
Conclusion: This study shows that the polymorphisms CTGF rs9399005C and CTGF rs6918698G predispose to FIP and CTGF rs6918698G also to sporadic IPF.
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