NOTCH3 T6746C and TP53 P72R Polymorphisms Are Associated with the Susceptibility to Diffuse Cutaneous Systemic Sclerosis

Introduction. NOTCH pathway and TP53 protein are involved in the development of fibrosis and autoimmune disorders, respectively. The aim of this study was to evaluate the role of single nucleotide polymorphisms (SNPs) of NOTCH3 and TP53 genes and serum anti-TP53 antibodies with the susceptibility, clinical subset of systemic sclerosis (SSc), and clinical profile of SSc patient, particularly with lung involvement and disease activity. Objects and Methods. 124 white Polish SSc patients (101 with limited cutaneous SSc–lcSSc, and 23 with diffuse cutaneous SSc–dcSSc) and 100 healthy individuals were included in the study. Patients were assessed for the presence of autoantibodies and interstitial lung disease. Two SNPs at position 6746 of NOTCH3 and TP53 genes and serum anti-TP53 antibodies with the susceptibility, clinical subset of systemic sclerosis (SSc), and clinical profile of SSc patient, particularly with lung involvement and disease activity. RESULTS: The genotypic frequencies of the NOTCH3 and p=0.03; χ(2) = 4.63). There was no significant difference between SSc patients and the control population in allele frequencies of both SNPs. The CT + CC genotypes of NOTCH3 and p=0.03; p=0.03; p=0.03; TP53 genes and serum anti-TP53 antibodies with the susceptibility, clinical subset of systemic sclerosis (SSc), and clinical profile of SSc patient, particularly with lung involvement and disease activity. p=0.03; CONCLUSION: The CT + CC genotypes of NOTCH3 gene and PR + RR genotypes of the TP53 gene increased the risk of dcSSc development. Moreover, genotypes of CT + CC were associated with the active form of SSc suggesting the role of the NOTCH pathway in the pathogenesis of this disease.NOTCH3 and TP53 genes and serum anti-TP53 antibodies with the susceptibility, clinical subset of systemic sclerosis (SSc), and clinical profile of SSc patient, particularly with lung involvement and disease activity.