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

Szymon Zmorzyński,Małgorzata Kowal,Wojciech Styk,Magdalena Wojcierowska-Litwin,Dorota Krasowska,Małgorzata Michalska-Jakubus,Irena Walecka,Agata Anna Filip

doi:10.1155/2020/8465971

Szymon Zmorzyński, Małgorzata Kowal + Show 6 more

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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; χ2 = 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.

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NOTCH pathway and TP53 protein are involved in the development of fibrosis and autoimmune disorders, respectively. e 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, with lung involvement and disease activity
Systemic sclerosis (SSc) is a connective tissue disease characterized by vascular dysfunction, the presence of autoantibodies, and inflammatory-driven fibrosis of the skin and internal organs [1, 2]. e disease manifests clinically as limited cutaneous SSc or diffuse cutaneous SSc distinguished mainly on the pattern of skin involvement: lcSSc form is characterized by skin involvement restricted to hands, face, forearms, and feet, whereas in dcSSc skin sclerosis extends proximal to the elbow and may involve truncal areas [3,4,5]
Genotyping was successful in all individuals. e HardyWeinberg equilibrium (HWE) test showed that genotypic frequencies of NOTCH3 gene for SSc patients diverged significantly from the equilibrium, which indicates a possible association of these genotypes with the disease (Table 3). e frequencies of TP53 genotypes were in HWE

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Introduction

NOTCH pathway and TP53 protein are involved in the development of fibrosis and autoimmune disorders, respectively. e 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, with lung involvement and disease activity. E 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, with lung involvement and disease activity. E levels of anti-TP53 antibodies were not related to studied SNPs and clinical parameters of SSc including the presence of specific antibodies and interstitial lung disease. Interstitial lung disease is observed in up to 50% of SSc patients and is featured by activation of the NOTCH pathway involved in the differentiation of myofibroblasts [6, 7]. TP53 protein acts as a transcription factor, which regulates the expression of genes involved in cell cycle progression, cell growth, and apoptosis It is encoded by the TP53 gene (locus 17p13.1). Increased expression of TP53 is consistent with a higher level of apoptosis [14]

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