Understanding the Impact of CTGF Promoter and Exon Variants on Wounding and Disease Associated Risks

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Smith, Lorna
In the United States, cardiovascular disease is the leading cause of death. After a heart attack, cardiac tissue becomes damaged, and the subsequent repair often results in fibrosis and poor heart function. Connective Tissue Growth Factor (CTGF) is a gene involved in healthy wound healing, and increased CTGF expression has been shown to impact fibrosis. Previous research in the Doherty lab has found associations between CTGF exon variants and cardiovascular disease (CVD)-related phenotypes and comorbidities. Additionally, the promoter region of CTGF was investigated for genetic variants due to its impact on gene expression. Cheek cells were collected from volunteers in the PSU population and DNA was extracted, sequenced, and analyzed for genetic variants in both the promoter and exons of CTGF. Volunteers also completed a survey about CVD-related phenotypes in their family history. An inflammatory wound healing model was utilized in order to determine the impact of specific exon variants on CTGF expression. One exon variant, G1355T, significantly impacted CTGF expression, and was previously associated to a decreased family history of CVD. Through targeted sequencing, we identified two previously published CTGF promoter variants. One variant, G-745/-945C, had been formerly found to increase CTGF expression and increase the likelihood for developing systemic sclerosis (SSc). Going forward, understanding possible genetic predispositions and the role of CTGF will help to identify those most at risk of developing fibrosis prior to a heart attack/disease onset.